Functional and Structural Investigation of Myenteric Neurons in the Human Colon.

Background And Aims: The enteric nervous system independently controls gastrointestinal function including motility, which is primarily mediated by the myenteric plexus, therefore also playing a crucial role in functional intestinal disorders. Live recordings from human myenteric neurons proved to be challenging due to technical difficulties. Using the neuroimaging technique, we are able to record human colonic myenteric neuronal activity and investigate their functional properties in a large cohort of patients.

High-density multielectrode arrays bring cellular resolution to neuronal activity and network analyses of corticospinal motor neurons.

Corticospinal motor neurons (CSMN), located in the motor cortex of the brain, are one of the key components of the motor neuron circuitry. They are in part responsible for the initiation and modulation of voluntary movement, and their degeneration is the hallmark for numerous diseases, such as amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegia, and primary lateral sclerosis. Cortical hyperexcitation followed by in-excitability suggests the early involvement of cortical dysfunction in ALS pathology.

Changes of peripheral serotonin in the psychosocially stressed rats treated with linden honey.

This study aimed to investigate the effects of linden honey in maintaining the stability of peripheral serotonergic system in the psychosocially stressed rats. In this experiment we examined concentration of serotonin (5-HT) in Serbian linden honey, as well as concentrations of 5-HT and MAO A activity in the blood of chronically stressed rats treated with linden honey. The investigated parameters were quantified using HPLC method with electrochemical detector, HPLC method with a fluorescent detector, and assay of enzyme activities.

The Cdk inhibitor dinaciclib as a promising anti-tumorigenic agent in biliary tract cancer.

Biliary tract cancer (BTC) is a rare malignancy with rising incidence. The therapeutic options are limited and the overall survival remains poor. Cyclin-dependent kinases, drivers of cell cycle and transcription have numerous biological functions and are known to be dysregulated in numerous tumor entities.

Targeting mutation sites in the omicron variant of SARS-CoV-2 as potential therapeutic strategy against COVID-19 by antiretroviral drugs.

The multiple mutation of the spike (S) protein of the Omicron SARS-CoV-2 variant is a major concern, as it has been implicated in the severity of COVID-19 and its complications. These mutations have been attributed to COVID-19-infected immune-compromised individuals, with HIV patients being suspected to top the list. The present study investigated the mutation of the S protein of the omicron variant in comparison to the Delta and Wuhan variants.

Bone Mineral Density and First Line Imaging with [F]fluorocholine PET/CT in Normocalcemic and Hypercalcemic Primary Hyperparathyroidism: Results from a Single Center.

: Primary hyperparathyroidism (PHPT) is associated with normal or elevated calcium levels and affects bone mineral density. The proportion of cases predisposed to metabolic bone disease is unknown in patients with PHPT. The aim of this study was to assess bone mineral density and bone quality in patients with normo- or hypercalcemic primary hyperparathyroidism undergoing baseline parathyroid gland assessment with [F]fluorocholine PET/CT imaging.

Experts fail to reliably detect AI-generated histological data.

AI-based methods to generate images have seen unprecedented advances in recent years challenging both image forensic and human perceptual capabilities. Accordingly, these methods are expected to play an increasingly important role in the fraudulent fabrication of data. This includes images with complicated intrinsic structures such as histological tissue samples, which are harder to forge manually.

Water in peripheral TM-interfaces of Orai1-channels triggers pore opening.

The activation of the Ca-channel Orai1 via the physiological activator stromal interaction molecule 1 (STIM1) requires structural rearrangements within the entire channel complex involving a series of gating checkpoints. Focusing on the gating mechanism operating along the peripheral transmembrane domain (TM) 3/TM4-interface, we report here that some charged substitutions close to the center of TM3 or TM4 lead to constitutively active Orai1 variants triggering nuclear factor of activated T-cell (NFAT) translocation into the nucleus. Molecular dynamics simulations unveil that this gain-of-function correlates with enhanced hydration at peripheral TM-interfaces, leading to increased local structural flexibility of the channel periphery and global conformational changes permitting pore opening.

Cytomegalovirus infection of the fetal brain: intake of aspirin during pregnancy blunts neurodevelopmental pathogenesis in the offspring.

Background: Congenital cytomegalovirus (CMV) infections represent one leading cause of human neurodevelopmental disorders. Despite their high prevalence and severity, no satisfactory therapy is available and pathophysiology remains elusive. The pathogenic involvement of immune processes occurring in infected developing brains has been increasingly documented.

Dicer-2 mutations in cells lead to a diminished antiviral function against Rift Valley fever virus and Bunyamwera virus infection.

Mosquitoes are known to transmit different arthropod-borne viruses belonging to various virus families. The exogenous small interfering RNA pathway plays an important role in the mosquito defence against such virus infections, with Dicer-2 (Dcr2) as one of the key proteins that initiates the cleavage of viral dsRNAs into 21 nt long virus-derived small interfering RNAs. Previous data identified the importance of various motifs in Dcr2 for its small interfering RNA (siRNA)-mediated antiviral activity.

Critical transitions in pancreatic islets.

Calcium signals in pancreatic cells collectives show a sharp transition from uncorrelated to correlated state resembling a phase transition as the slowly increasing glucose concentration crosses the tipping point. However, the exact nature or the order of this phase transition is not well understood. Using confocal microscopy to record the collective calcium activation of cells in an intact islet under changing glucose concentration in increasing and then decreasing way, we first show that in addition to the sharp transition, the coordinated calcium response exhibits a hysteresis indicating a critical, first order transition.

mVOC 4.0: a database of microbial volatiles.

Metabolomic microbiome research has become an important topic for understanding agricultural, ecological as well as health correlations. Only the determination of both the non-volatile and the volatile organic compound (mVOC) production by microorganisms allows a holistic view for understanding the complete potential of metabolomes and metabolic capabilities of bacteria. In the recent past, more and more bacterial headspaces and culture media were analyzed, leading to an accumulation of about 3500 mVOCs in the updated mVOC 4.

A novel gene variant in the voltage-dependent Kv3.3 channel in an atypical form of SCA13 with dominant central vertigo.

Potassium channel mutations play an important role in neurological diseases, such as spinocerebellar ataxia (SCA). SCA is a heterogeneous autosomal-dominant neurodegenerative disorder with multiple sub-entities, such as SCA13, which is characterized by mutations in the voltage-gated potassium channel Kv3.3 ().

Influence of N- and/or P-restriction on bone metabolism in young goats.

Ruminants can recycle nitrogen (N) and phosphorus (P), which are essential for vital body processes. Reduced N- and P-intake in ruminants is desirable for economic and ecologic reasons. Simultaneous modulation of mineral homoeostasis and bone metabolism occurs in young goats.

Calcium-permeable AMPA receptors govern PV neuron feature selectivity.

The brain helps us survive by forming internal representations of the external world. Excitatory cortical neurons are often precisely tuned to specific external stimuli. However, inhibitory neurons, such as parvalbumin-positive (PV) interneurons, are generally less selective.

Association of serum zinc with mineral stress in chronic kidney disease.

Background: The excessive cardiovascular mortality of patients with chronic kidney disease (CKD) could be linked to mineral stress, the biological consequence of calcium-phosphate nanoparticle exposure. This study investigated whether zinc is associated with mineral stress markers in CKD.

Methods: inc and T50 (serum calcification propensity) as well as hydrodynamic radius of secondary calciprotein particles (CPP2) were measured in blood donors and CKD patients with/out dialysis.

Oligodendroglial fatty acid metabolism as a central nervous system energy reserve.

Brain function requires a constant supply of glucose. However, the brain has no known energy stores, except for glycogen granules in astrocytes. In the present study, we report that continuous oligodendroglial lipid metabolism provides an energy reserve in white matter tracts.

Recognizing and preventing unacknowledged prescribing errors associated with polypharmacy.

Background: Prescribing errors put an enormous burden on health and the economy, claiming implementation of effective methods to prevent/reduce them. Polypharmacy regimens (five or more drugs) are highly prone to unacknowledged prescribing errors, since the complex network of drug-drug interactions, guidelines and contraindications is challenging to be adequately evaluated in the prescription phase, especially if different doctors are involved. Clinical decision support systems aimed at polypharmacy evaluation may be crucial to recognize and correct prescribing errors.