Systematic mapping of mitochondrial calcium uniporter channel (MCUC)-mediated calcium signaling networks.

The mitochondrial calcium uniporter channel (MCUC) mediates mitochondrial calcium entry, regulating energy metabolism and cell death. Although several MCUC components have been identified, the molecular basis of mitochondrial calcium signaling networks and their remodeling upon changes in uniporter activity have not been assessed. Here, we map the MCUC interactome under resting conditions and upon chronic loss or gain of mitochondrial calcium uptake.

Opposing Effects of Cannabidiol in Patient-derived Neuroendocrine Tumor, Pheochromocytoma/Paraganglioma Primary Cultures.

Context: Treatment options for advanced neuroendocrine tumors (NETs), pheochromocytomas and paragangliomas (PPGLs) are still limited. In recent years, antitumor effects of cannabinoids have been reported; however, there are only very limited data available in NETs or PPGLs.

Objective: Investigation of the effects of cannabidiol (CBD) on patient-derived human NET/PPGL primary cultures and on NET/PPGL cell lines.

Genes in Gastric Cancer: A Tumor-Suppressive Role for .

Tribbles pseudokinases (TRIB1-3) are important signaling modulators involved in several cancers. However, their function in gastric cancer (GC) remains undefined. GC is still a deadly disease since the lack of sensitive and specific biomarkers for early diagnosis and therapy response prediction negatively affects patients' outcome.

Animal and Cell Culture Models of PPGLs - Achievements and Limitations.

Research on rare tumors heavily relies on suitable models for basic and translational research. Paragangliomas (PPGL) are rare neuroendocrine tumors (NET), developing from adrenal (pheochromocytoma, PCC) or extra-adrenal (PGL) chromaffin cells, with an annual incidence of 2-8 cases per million. While most PPGL cases exhibit slow growth and are primarily treated with surgery, limited systemic treatment options are available for unresectable or metastatic tumors.

Regulation of epinephrine biosynthesis in HRAS-mutant paragangliomas.

The biochemical phenotype of paragangliomas (PGLs) is highly dependent on the underlying genetic background and tumor location. PGLs at extra-adrenal locations usually do not express phenylethanolamine N-methyltransferase (PNMT), the enzyme required for epinephrine production, which was explained by the absence of glucocorticoids. PGLs with pathogenic variants (PVs) in Harvey rat sarcoma viral oncogene homolog (HRAS) can occur in or outside of the adrenal, but always synthesize epinephrine independently of the localization.

Simultaneous magnetic resonance imaging of pH, perfusion and renal filtration using hyperpolarized C-labelled Z-OMPD.

pH alterations are a hallmark of many pathologies including cancer and kidney disease. Here, we introduce [1,5-C]Z-OMPD as a hyperpolarized extracellular pH and perfusion sensor for MRI which allows to generate a multiparametric fingerprint of renal disease status and to detect local tumor acidification. Exceptional long T of two minutes at 1 T, high pH sensitivity of up to 1.

Cellenium-a scalable and interactive visual analytics app for exploring multimodal single-cell data.

Summary: Multimodal single-cell sequencing data provide detailed views into the molecular biology of cells. To allow for interactive analyses of such rich data and to readily derive insights from it, new analysis solutions are required. In this work, we present Cellenium, our new scalable visual analytics web application that enables users to semantically integrate and organize all their single-cell RNA-, ATAC-, and CITE-sequencing studies.

Are electrophysiological correlates of response inhibition linked to impulsivity and compulsivity? A machine-learning analysis of a Go/Nogo task.

Heightened impulsivity and compulsivity are often found in association with both dysfunctional everyday behavior and with psychopathology. Impulsivity and compulsivity are also linked to alterations in behavioral response inhibition and its electrophysiological correlates. However, they are rarely examined jointly and their effect outside of clinical samples is still disputed.

Morphometrics of Kept as Laboratory Animals.

Morphometric data that provide information on body conditions can be used to monitor the health and well-being of animals. In laboratory animals, they can help to evaluate the stress due to experiments or treatments, following the 3R principles. The aim of the present study was to obtain morphometric data of male and female African clawed frogs, Xenopus laevis, as the bases for body condition evaluations.

Negative effects of forest gaps on dung removal in a full-factorial experiment.

Ecosystem functioning may directly or indirectly-via change in biodiversity-respond to land use. Dung removal is an important ecosystem function central for the decomposition of mammal faeces, including secondary seed dispersal and improved soil quality. Removal usually increases with dung beetle diversity and biomass.

Angpt2/Tie2 autostimulatory loop controls tumorigenesis.

Invasive nonfunctioning (NF) pituitary neuroendocrine tumors (PitNETs) are non-resectable neoplasms associated with frequent relapses and significant comorbidities. As the current therapies of NF-PitNETs often fail, new therapeutic targets are needed. The observation that circulating angiopoietin-2 (ANGPT2) is elevated in patients with NF-PitNET and correlates with tumor aggressiveness prompted us to investigate the ANGPT2/TIE2 axis in NF-PitNETs in the GH3 PitNET cell line, primary human NF-PitNET cells, xenografts in zebrafish and mice, and in MENX rats, the only autochthonous NF-PitNET model.

Imaging pheochromocytoma in small animals: preclinical models to improve diagnosis and treatment.

Pheochromocytomas (PCCs) and paragangliomas (PGLs), together referred to as PPGLs, are rare chromaffin cell-derived tumors. They require timely diagnosis as this is the only way to achieve a cure through surgery and because of the potentially serious cardiovascular complications and sometimes life-threatening comorbidities that can occur if left untreated. The biochemical diagnosis of PPGLs has improved over the last decades, and the knowledge of the underlying genetics has dramatically increased.

Aberrant neural representation of food stimuli in women with acute anorexia nervosa predicts treatment outcome and is improved in weight restored individuals.

Anorexia nervosa (AN) has been associated with altered reward processing. We recently reported greater neural response in secondary visual areas when processing visual food stimuli in acutely underweight AN patients (acAN). In order to examine whether the observed alterations are indicative of acute undernutrition or a potential trait marker of AN, we set out to assess neural responses in acAN and in individuals weight-recovered from AN (recAN).

Brain state kinematics and the trajectory of task performance improvement.

Dimensionality reduction techniques offer a unique perspective on brain state dynamics, in which systems-level activity can be tracked through the engagement of a small number of component trajectories. Used in combination with neuroimaging data collected during the performance of cognitive tasks, these approaches can expose the otherwise latent dimensions upon which the brain reconfigures in order to facilitate cognitive performance. Here, we utilized Principal Component Analysis to transform parcellated BOLD timeseries from an fMRI dataset in which 70 human subjects performed an instruction based visuomotor learning task into orthogonal low-dimensional components.

Real-Life Self-Control is Predicted by Parietal Activity During Preference Decision Making: A Brain Decoding Analysis.

Despite its relevance for health and education, the neurocognitive mechanism of real-life self-control is largely unknown. While recent research revealed a prominent role of the ventromedial prefrontal cortex in the computation of an integrative value signal, the contribution and relevance of other brain regions for real-life self-control remains unclear. To investigate neural correlates of decisions in line with long-term consequences and to assess the potential of brain decoding methods for the individual prediction of real-life self-control, we combined functional magnetic resonance imaging during preference decision making with ecological momentary assessment of daily self-control in a large community sample (N = 266).

Disrupted Salience and Cingulo-Opercular Network Connectivity During Impaired Rapid Instructed Task Learning in Schizophrenia.

Rapid instructed task learning (RITL) is the uniquely human ability to transform task information into goal-directed behavior without relying on trial-and-error learning. RITL is a core cognitive process supported by functional brain networks. In patients with schizophrenia, RITL ability is impaired, but the role of functional network connectivity in these RITL deficits is unknown.

Mutation of the Cell Cycle Regulator p27kip1 Drives Pseudohypoxic Pheochromocytoma Development.

Background: Pseudohypoxic tumors activate pro-oncogenic pathways typically associated with severe hypoxia even when sufficient oxygen is present, leading to highly aggressive tumors. Prime examples are pseudohypoxic pheochromocytomas and paragangliomas (p-PPGLs), neuroendendocrine tumors currently lacking effective therapy. Previous attempts to generate mouse models for p-PPGLs all failed.

Fast Estimation of L1-Regularized Linear Models in the Mass-Univariate Setting.

In certain modeling approaches, activation analyses of task-based fMRI data can involve a relatively large number of predictors. For example, in the encoding model approach, complex stimuli are represented in a high-dimensional feature space, resulting in design matrices with many predictors. Similarly, single-trial models and finite impulse response models may also encompass a large number of predictors.

miR-34a is upregulated in AIP-mutated somatotropinomas and promotes octreotide resistance.

Pituitary adenomas (PAs) are intracranial tumors associated with significant morbidity due to hormonal dysregulation, mass effects and have a heavy treatment burden. Growth hormone (GH)-secreting PAs (somatotropinomas) cause acromegaly-gigantism. Genetic forms of somatotropinomas due to germline AIP mutations (AIPmut+) have an early onset and are aggressive and resistant to treatment with somatostatin analogs (SSAs), including octreotide.

The Structure of Psychopathology in a Sample of Clinically Referred, Emotionally Dysregulated Early Adolescents.

This investigation answers and amplifies calls to model the transdiagnostic structure of psychopathology in clinical samples of early adolescents and using stringent psychometric criteria. In 162 clinically referred, clinically evaluated 11-13-year-olds, we compared a correlated two-factor model, containing latent internalizing and externalizing factors, to a bifactor model, which added a transdiagnostic general factor. We also evaluated the bifactor model psychometrically, including criterion validity with broad indicators of psychosocial functioning.