Tumor Necrosis Factor-Alpha Inhibits the Replication of Patient-Derived Archetype BK Polyomavirus While Activating Rearranged Strains.

To date, no drugs are approved for BK polyomavirus (BKPyV) reactivation, a major cause of nephropathy after kidney transplantation. Recently, tumor necrosis factor-α (TNF-α) blockade has been proposed as a promising therapy, however, the effect of TNF-α on the clinically most common archetype (ww) BKPyV remained unclear. Assays in primary renal proximal tubule epithelial cells (RPTEC) allowed efficient replication only of BKPyV strains with rearranged (rr) non-coding control regions (NCCR), which may develop at later disease stages, but not of ww-BKPyV.

NLRP3-mediated glutaminolysis controls microglial phagocytosis to promote Alzheimer's disease progression.

Activation of the NLRP3 inflammasome has been implicated in the pathogenesis of Alzheimer's disease (AD) via the release of IL-1β and ASC specks. However, whether NLRP3 is involved in pathways beyond this remained unknown. Here, we found that Aβ deposition in vivo directly triggered NLRP3 activation in APP/PS1 mice, which model many features of AD.

Oligodendrocyte precursor cells facilitate neuronal lysosome release.

Oligodendrocyte precursor cells (OPCs) shape brain function through many non-canonical regulatory mechanisms beyond myelination. Here we show that OPCs form contacts with their processes on neuronal somata in a neuronal activity-dependent manner. These contacts facilitate exocytosis of neuronal lysosomes.

Distribution of spine classes shows intra-neuronal dendritic heterogeneity in mouse cortex.

Significance: Neuronal dendritic spines are central elements for memory and learning. Their morphology correlates with synaptic strength and is a proxy for function. Classic light microscopy cannot resolve spine morphology well, and techniques with higher resolution (electron microscopy and super-resolution light microscopy) typically do not provide spine data in large fields of view, e.

Tumor budding and lymphovascular invasion as prognostic factors in p16-positive oropharyngeal squamous cell carcinomas.

Background: We aimed to validate the prognostic significance of tumor budding (TB) in p16-positive oropharyngeal squamous cell carcinomas (OPSCC).

Methods: We analyzed digitized H&E-stained slides from a multicenter cohort of five large university centers consisting of n = 275 cases of p16-positive OPSCC. We evaluated TB along with other histological parameters (morphology, tumor-stroma-ratio, lymphovascular invasion (LVI), perineural invasion) and calculated survival outcomes using both univariate and multivariate analyses.

Improved ex vivo fluorescence imaging of human head and neck cancer using the peptide tracer TPP-IRDye800 targeting membrane-bound Hsp70 on tumor cells.

Background: The primary goal of surgery in HNSCC is the complete resection of tumor cells with maximum preservation of normal tissue. The membrane Hsp70-targeting fluorescence labelled peptide TPP-IRDye800 represents a promising tool for real-time intraoperative tumor visualization, enabling the detection of true tumor margins, critical isles of high-grade dysplasia and LN metastases.

Methods: Membrane Hsp70 (mHsp70) expression on HNSCC cell lines and primary HNSCC was determined by flow cytometry and fluorescence microscopy using FITC-conjugated mAb cmHsp70.

Leaf transcriptomes from C3, C3-C4 intermediate, and C4Neurachne species give insights into C4 photosynthesis evolution.

The C4 photosynthetic pathway is hypothesized to have evolved from the ancestral C3 pathway through progressive changes in leaf anatomy and biochemistry with extant C3-C4 photosynthetic intermediate species representing phenotypes between species demonstrating full C3 and full C4 states. The Australian endemic genus Neurachne is the only known grass group that contains distinct, closely related species that carry out C3, C3-C4 intermediate, or C4 photosynthesis. To explore and understand the molecular mechanisms underlying C4 photosynthesis evolution in this genus, leaf transcriptomes were generated from two C3, three photosynthetic intermediate (proto-Kranz, C2-like, and C2), and two C4Neurachne species.

Telemedical management of symptomatic COVID-19 outpatients.

Background: COVID-19 remains a challenge to individual health and healthcare resources worldwide. Telemedical surveillance might minimise hospitalisation and direct patient-physician contacts. Yet, randomised clinical trials evaluating telemedical management of COVID-19 patients are lacking.

Dysphoric Milk Ejection Reflex (D-MER): A Novel Neuroendocrine Condition with Psychiatric Manifestations.

Learning Objectives After Participating In This Cme Activity, Readers Should Be Better Able To: • Describe how the symptoms of dysphoric milk ejection reflex (D-MER) affect nursing patients.• Discuss how physicians, psychologists, and clinicians can support their patients experiencing D-MER.

Abstract: Dysphoric milk ejection reflex (D-MER) is characterized by a sudden onset of profoundly negative emotions that are temporally linked to milk letdown when breastfeeding or pumping breast milk.

From Planning Stage Towards FAIR Data: A Practical Metadatasheet For Biomedical Scientists.

Datasets consist of measurement data and metadata. Metadata provides context, essential for understanding and (re-)using data. Various metadata standards exist for different methods, systems and contexts.

Single-Dose Synthetic Psilocybin With Psychotherapy for Treatment-Resistant Bipolar Type II Major Depressive Episodes: A Nonrandomized Open-Label Trial.

Importance: Bipolar II disorder (BDII) is a debilitating condition frequently associated with difficult-to-treat depressive episodes. Psilocybin has evidence for rapid-acting antidepressant effects but has not been investigated in bipolar depression.

Objective: To establish the safety and efficacy of psilocybin in patients with BDII in a current depressive episode.

Cutting Edge: STING Induces ACLY Activation and Metabolic Adaptations in Human Macrophages through TBK1.

The 2'3'-cyclic GMP-AMP (cGAMP) synthase (cGAS)-stimulator of IFN genes (STING) pathway can sense infection and cellular stress by detecting cytosolic DNA. Upon ligand binding, cGAS produces the cyclic dinucleotide messenger cGAMP, which triggers its receptor STING. Active STING initiates gene transcription through the transcription factors IFN regulatory factor 3 (IRF3) and NF-κB and induces autophagy, but whether STING can cause changes in the metabolism of macrophages is unknown.

STED microscopy reveals dendrite-specificity of spines in turtle cortex.

Dendritic spines are key structures for neural communication, learning and memory. Spine size and shape probably reflect synaptic strength and learning. Imaging with superresolution STED microscopy the detailed shape of the majority of the spines of individual neurons in turtle cortex (Trachemys scripta elegans) revealed several distinguishable shape classes.

Procedural success in transaxillary transcatheter aortic valve implantation according to type of transcatheter heart valve: results from the multicenter TAXI registry.

Background: Transaxillary (TAx) transcatheter aortic valve implantation (TAVI) is a preferred alternative access in patients ineligible for transfemoral TAVI.

Aims: This study used the Trans-AXillary Intervention (TAXI) registry to compare procedural success according to different types of transcatheter heart valves (THV).

Methods: For the TAXI registry anonymized data of patients treated with TAx-TAVI were collected from 18 centers.

Tumour budding-based grading as independent prognostic biomarker in HPV-positive and HPV-negative head and neck cancer.

Background: The prognostic significance of tumour budding (TB) and minimal cell nest size (MCNS) was shown in human papillomavirus (HPV)-negative head and neck squamous cell carcinomas (HNSCC). However, the optimisation of cutpoints, the prognostic impact in HPV-positive HNSCC, and the comparison with other histopathological grading systems are insufficiently investigated.

Methods: TB and MCNS were analysed digitally in 1 and 10 high-power fields (HPF) of 331 HPV-positive and HPV-negative cases from TCGA.

SiMeEx, a simplified method for metabolite extraction of adherent mammalian cells.

A reliable method for metabolite extraction is central to mass spectrometry-based metabolomics. However, existing methods are lengthy, mostly due to the step of scraping cells from cell culture vessels, which restricts metabolomics in broader application such as lower cell numbers and high-throughput studies. Here, we present a simplified metabolite extraction (SiMeEx) method, to efficiently and quickly extract metabolites from adherent mammalian cells.

Life-long deficits in social adaptation and the frontal lobes: New evidence, seventy-five years after Ackerly and Benton's landmark case report of JP.

The case of JP, reported by Ackerly and Benton in 1948 with a detailed follow-up by Ackerly in 1964, stands as the index case of developmental prefrontal damage and its impact on social adaptation. Although the 1948 case report included findings from a 1933 pneumoencephalogram and exploratory craniotomy, a definitive cause was never established for JP's prefrontal damage. Etiologies were never determined for the left-sided seizures that occurred when JP was age four, nor for the progressive anterograde amnesia that JP developed in middle age.