Impaired Presynaptic Function Contributes Significantly to the Pathology of Glycine Receptor Autoantibodies.

Background And Objectives: Autoantibodies (aAbs) against glycine receptors (GlyRs) are mainly associated with the rare neurologic diseases stiff person syndrome (SPS) and progressive encephalomyelitis with rigidity and myoclonus (PERM). GlyR aAbs are also found in other neurologic diseases such as epilepsy. The aAbs bind to different GlyR α-subunits and, more rarely, also to the GlyR β-subunit.

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.

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.

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.

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 ().

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.

Augmentative effects of leukemia inhibitory factor reveal a critical role for TYK2 signaling in vascular calcification.

Medial vascular calcification in chronic kidney disease (CKD) involves pro-inflammatory pathways induced by hyperphosphatemia. Several interleukin 6 family members have been associated with pro-calcific effects in vascular smooth muscle cells (VSMCs) and are considered as therapeutic targets. Therefore, we investigated the role of leukemia inhibitory factor (LIF) during VSMC calcification.

Citrate-Buffered, Magnesium-Enriched Dialysate on Calcification Propensity in Hemodialysis Patients - The CitMag Study.

Introduction: Serum calcification propensity (T50 time) is associated with mortality in patients on dialysis. Several solitary interventions improve T50. However, whether a combination of interventions yields further increases in T50 is unknown.

KCNQ1 is an essential mediator of the sex-dependent perception of moderate cold temperatures.

Low temperatures and cooling agents like menthol induce cold sensation by activating the peripheral cold receptors TRPM8 and TRPA1, cation channels belonging to the TRP channel family, while the reduction of potassium currents provides an additional and/or synergistic mechanism of cold sensation. Despite extensive studies over the past decades to identify the molecular receptors that mediate thermosensation, cold sensation is still not fully understood and many cold-sensitive peripheral neurons do not express the well-established cold sensor TRPM8. We found that the voltage-gated potassium channel KCNQ1 (Kv7.

Popeye domain containing proteins modulate the voltage-gated cardiac sodium channel Nav1.5.

Popeye domain containing (POPDC) proteins are predominantly expressed in the heart and skeletal muscle, modulating the K potassium channel TREK-1 in a cAMP-dependent manner. and variants cause cardiac conduction disorders with or without muscular dystrophy. Searching for POPDC2-modulated ion channels using a functional co-expression screen in oocytes, we found POPDC proteins to modulate the cardiac sodium channel Nav1.

Small fibre neuropathy in Fabry disease: a human-derived neuronal disease model and pilot data.

Acral burning pain triggered by fever, thermal hyposensitivity and skin denervation are hallmarks of small fibre neuropathy in Fabry disease, a life-threatening X-linked lysosomal storage disorder. Variants in the gene encoding alpha-galactosidase A may lead to impaired enzyme activity with cellular accumulation of globotriaosylceramide. To study the underlying pathomechanism of Fabry-associated small fibre neuropathy, we generated a neuronal disease model using patient-derived induced pluripotent stem cells from three Fabry patients and one healthy control.

Serum T predicts cardiovascular mortality in individuals with type 2 diabetes: A prospective cohort study.

Background And Aims: Individuals with type 2 diabetes (T2D) have a higher risk of cardiovascular disease, compared with those without T2D. The serum T50 test captures the transformation time of calciprotein particles in serum. We aimed to assess whether serum T50 predicts cardiovascular mortality in T2D patients, independent of traditional risk factors.

Detecting high-risk neighborhoods and socioeconomic determinants for common oral diseases in Germany.

Background: Ideally, health services and interventions to improve dental health should be tailored to local target populations. But this is not the standard. Little is known about risk clusters in dental health care and their evaluation based on small-scale, spatial data, particularly among under-represented groups in health surveys.

Gpcpd1-GPC metabolic pathway is dysfunctional in aging and its deficiency severely perturbs glucose metabolism.

Skeletal muscle plays a central role in the regulation of systemic metabolism during lifespan. With aging, this function is perturbed, initiating multiple chronic diseases. Our knowledge of mechanisms responsible for this decline is limited.

Sympathetic-Immune Interactions during Different Types of Immune Challenge.

Background: The neuro-endocrine regulation of immune functions is based on a complex network of interactions. As part of this series of articles, we refer here to immune-sympathetic interactions that are triggered by different types of immune challenge.

Summary: We mention the initial hypothesis that led to the proposal that the sympathetic nervous system (SNS) is involved in immunoregulation.

Adam, amigo, brain, and K channel.

Voltage-dependent K (Kv) channels are diverse, comprising the classical  - Kv2,  - Kv1,  - Kv4, and  - Kv3 families. The family alone consists of Kv1.1, Kv1.

Exploring the Skin Brain Link: Biomarkers in the Skin with Implications for Aging Research and Alzheimer's Disease Diagnostics.

Neurodegenerative diseases, including Alzheimer's disease (AD), are challenging to diagnose. Currently the field must rely on imperfect diagnostic modalities. A recent study identified differences in several key bio-mechano-physiological parameters of the skin between AD patients and healthy controls.

Calprotectin is a contributor to and potential therapeutic target for vascular calcification in chronic kidney disease.

Vascular calcification is an important risk factor for cardiovascular (CV) mortality in patients with chronic kidney disease (CKD). It is also a complex process involving osteochondrogenic differentiation of vascular smooth muscle cells (VSMCs) and abnormal deposition of minerals in the vascular wall. In an observational, multicenter European study, including 112 patients with CKD from Spain and 171 patients on dialysis from France, we used serum proteome analysis and further validation by ELISA to identify calprotectin, a circulating damage-associated molecular pattern protein, as being independently associated with CV outcome and mortality.

Ferroptosis and PPAR-gamma in the limelight of brain tumors and edema.

Human malignant brain tumors such as gliomas are devastating due to the induction of cerebral edema and neurodegeneration. A major contributor to glioma-induced neurodegeneration has been identified as glutamate. Glutamate promotes cell growth and proliferation in variety of tumor types.

Associations of systemic oxidative stress with functional outcomes after ST-segment elevation myocardial infarction.

Background: Ischemia-reperfusion is accompanied by oxidative stress. Serum free thiols (FTs; sulfhydryl groups) reliably reflect systemic oxidative stress. This study evaluates longitudinal changes in FTs and their associations with outcomes after ST-segment elevation myocardial infarction (STEMI).