An AMP-activated protein kinase-PGC-1α axis mediates metabolic plasticity in glioblastoma.

Glioblastoma, the most frequent primary malignant brain tumour in adults, is characterised by profound yet dynamic hypoxia and nutrient depletion. To sustain survival and proliferation, tumour cells are compelled to acquire metabolic plasticity with the induction of adaptive metabolic programs. Here, we interrogated the pathways necessary to enable processing of nutrients other than glucose.

The Proteomics Standards Initiative Standardized Formats for Spectral Libraries and Fragment Ion Peak Annotations: mzSpecLib and mzPAF.

Mass spectral libraries are collections of reference spectra, usually associated with specific analytes from which the spectra were generated, that are used for further downstream analysis of new spectra. There are many different formats used for encoding spectral libraries, but none have undergone a standardization process to ensure broad applicability to many applications. As part of the Human Proteome Organization Proteomics Standards Initiative (PSI), we have developed a standardized format for encoding spectral libraries, called mzSpecLib (https://psidev.

Mapping illegal trade routes of live cheetahs from the Horn of Africa to the Arabian Peninsula.

Less than 7000 cheetahs (Acinonyx jubatus) persist in Africa. Although human-wildlife conflict, habitat degradation, and loss of prey are major threats to cheetah populations, illegal trade in live cubs for pets may have the most significant impact on populations in the Horn of Africa. We developed a novel, stepwise decision support tool to predict probable trafficking routes by leveraging the power of distinct modeling approaches.

Metabolic and lifestyle factors accelerate disease onset and alter gut microbiome in inflammatory non-communicable diseases.

Background: Biomedical and lifestyle factors in Western populations have significantly shifted in recent decades, influencing public health and contributing to the increasing prevalence of non-communicable diseases (NCDs) that share inflammation as common pathology.

Methods: We investigated the relationship between these factors and 11 NCDs in the cross-sectional FoCus cohort (n = 1220), using logistic regression models. Associations with age-at-disease-onset were specifically analyzed for type 2 diabetes (T2D, low-grade chronic inflammation) and inflammatory bowel disease (IBD, high-grade chronic inflammation) in disease-specific cohorts (FoCus-T2D, n = 514; IBD-KC, n = 1110).

Fragility Index Analysis of the 2018 Clinical Practice Guidelines on Tranexamic Acid Use in Total Joint Arthroplasty.

Background: The 2018 American Association of Hip and Knee Surgeons clinical practice guideline (CPG) 'tranexamic acid use in total joint arthroplasty' evaluated the efficacy and safety of tranexamic acid in primary total joint arthroplasty. The following review assessed the statistical fragility of the randomized controlled trial (RCT) outcomes on which the CPG recommendations were based using a fragility analysis.

Methods: All dichotomous outcomes from the RCTs used to guide the CPG from its associated network, and direct meta-analyses were analyzed.

The XENONnT dark matter experiment.

The multi-staged XENON program at INFN Laboratori Nazionali del Gran Sasso aims to detect dark matter with two-phase liquid xenon time projection chambers of increasing size and sensitivity. The XENONnT experiment is the latest detector in the program, planned to be an upgrade of its predecessor XENON1T. It features an active target of 5.

[Histo- and molecular pathology in gastroenteropancreatic neuroendocrine neoplasms].

Neuroendocrine neoplasms are classified according to the WHO classification based on morphological criteria into neuroendocrine tumors, neuroendocrine carcinomas, and mixed neuroendocrine-non-neuroendocrine neoplasms. Neuroendocrine tumors are well differentiated neoplasms and show characteristic site-specific histological and molecular features, which is important for their clinical management. In cases dealing with metastasis, pathology often can help to identify the primary tumors using a small immunohistochemical marker panel.

Effects of oxidized LDL versus IL-1ß/TNF-ɑ/INFɣ on human gingival mesenchymal stem cells properties.

Aims: Oxidized low-density lipoprotein (oxLDL) is an important player in the course of metabolic inflammatory diseases. oxLDL was identified in the gingival crevicular fluid, denoting possible associations between oxLDL-induced inflammation and periodontal disease. The current investigation compared for the first-time direct effects of oxLDL to a cytokine cocktail of IL-1ß/TNF-ɑ/INF-γ on gingival mesenchymal stem cells' (G-MSCs) attributes.

A Handle on Mass Coincidence Errors in Sequencing of Antibodies by Bottom-up Proteomics.

Antibody sequences can be determined at 99% accuracy directly from the polypeptide product by using bottom-up proteomics techniques. Sequencing accuracy at the peptide level is limited by the isobaric residues leucine and isoleucine, incomplete fragmentation spectra in which the order of two or more residues remains ambiguous due to lacking fragment ions for the intermediate positions, and isobaric combinations of amino acids, of potentially different lengths, for example, GG = N and GA = Q. Here, we present several updates to Stitch (v1.

Reverse-engineering the anti-MUC1 antibody 139H2 by mass spectrometry-based de novo sequencing.

Mucin 1 (MUC1) is a transmembrane mucin expressed at the apical surface of epithelial cells at mucosal surfaces. MUC1 has a barrier function against bacterial invasion and is well known for its aberrant expression and glycosylation in adenocarcinomas. The MUC1 extracellular domain contains a variable number of tandem repeats (VNTR) of 20 amino acids, which are heavily -linked glycosylated.

The neuronal transcription factor MEIS2 is a calpain-2 protease target.

Tight control over transcription factor activity is necessary for a sensible balance between cellular proliferation and differentiation in the embryo and during tissue homeostasis by adult stem cells, but mechanistic details have remained incomplete. The homeodomain transcription factor MEIS2 is an important regulator of neurogenesis in the ventricular-subventricular zone (V-SVZ) adult stem cell niche in mice. We here identify MEIS2 as direct target of the intracellular protease calpain-2 (composed of the catalytic subunit CAPN2 and the regulatory subunit CAPNS1).

Into the Dark Serum Proteome: Personalized Features of IgG1 and IgA1 Repertoires in Severe COVID-19 Patients.

Serum proteomics has matured and is now able to monitor hundreds of proteins quantitatively in large cohorts of patients. However, the fine characteristics of some of the most dominant proteins in serum, the immunoglobulins, are in these studies often ignored, due to their vast, and highly personalized, diversity in sequences. Here, we focus exclusively on these personalized features in the serum proteome and distinctively chose to study individual samples from a low diversity population: elderly donors infected by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2).

Effect of Hyperbaric Oxygen and Inflammation on Human Gingival Mesenchymal Stem/Progenitor Cells.

The present study explores for the first time the effect of hyperbaric oxygen (HBO) on gingival mesenchymal stem cells' (G-MSCs) gene expression profile, intracellular pathway activation, pluripotency, and differentiation potential under an experimental inflammatory setup. G-MSCs were isolated from five healthy individuals ( = 5) and characterized. Single (24 h) or double (72 h) HBO stimulation (100% O2, 3 bar, 90 min) was performed under experimental inflammatory [IL-1β (1 ng/mL)/TNF-α (10 ng/mL)/IFN-γ (100 ng/mL)] and non-inflammatory micro-environment.

Searching for Heavy Dark Matter near the Planck Mass with XENON1T.

Multiple viable theoretical models predict heavy dark matter particles with a mass close to the Planck mass, a range relatively unexplored by current experimental measurements. We use 219.4 days of data collected with the XENON1T experiment to conduct a blind search for signals from multiply interacting massive particles (MIMPs).

Bioinformatics for wet-lab scientists: practical application in sequencing analysis.

Background: Genomics data is available to the scientific community after publication of research projects and can be investigated for a multitude of research questions. However, in many cases deposited data is only assessed and used for the initial publication, resulting in valuable resources not being exploited to their full depth. MAIN: A likely reason for this is that many wetlab-based researchers are not formally trained to apply bioinformatic tools and may therefore assume that they lack the necessary experience to do so themselves.

Relapsing Syndrome of Inappropriate Antidiuretic Hormone Production Responding to Tolvaptan Treatment in a Patient With a Micronodular Formation of the Posterior Pituitary Gland.

The syndrome of inappropriate ADH-secretion (SIADH) is a common cause of low sodium levels with diverse aetiology. Here, we report a case of a 41 years old male patient diagnosed with SIADH and a good response to Tolvaptan therapy. Of interest, as a potential unique cause, magnetic resonance imaging revealed a micronodular structure in the posterior pituitary, while no other common cause of SIADH could be identified.

The Introduction of an MR-Conditional Prototype for Cardiopulmonary Bypass Support: Technical Aspects and System Requirements.

Introduction: The use of cardiopulmonary bypass (CBP; also known as a heart-lung machine) in newborns with complex congenital heart defects may result in brain damage. Magnetic resonance imaging (MRI) assessments cannot be performed safely because the metal components used to construct CBP devices may elicit adverse effects on patients when they are placed in a magnetic field. Thus, this project aimed to develop a prototype MR-conditional circulatory support system that could be used to perform cerebral perfusion studies in animal models.

Svep1 is a binding ligand of Tie1 and affects specific aspects of facial lymphatic development in a Vegfc-independent manner.

Multiple factors are required to form functional lymphatic vessels. Here, we uncover an essential role for the secreted protein Svep1 and the transmembrane receptor Tie1 during the development of subpopulations of the zebrafish facial lymphatic network. This specific aspect of the facial network forms independently of Vascular endothelial growth factor C (Vegfc) signalling, which otherwise is the most prominent signalling axis in all other lymphatic beds.