Facial misfits accelerate stereotype-based associative learning.

Counterstereotypes challenge the deleterious effects that gender-typed beliefs exert on people's occupational aspirations and lifestyle choices. Surprisingly, however, the critical issue of how readily unexpected person-related knowledge can be acquired remains poorly understood. Accordingly, in two experiments in which the facial appearance of targets was varied to manipulate goodness-of-stereotype-fit (i.

Neuronopathic Gaucher disease: Rare in the West, common in the East.

Gaucher disease (GD) stands as one of the most prevalent lysosomal disorders, yet neuronopathic GD (nGD) is an uncommon subset characterized by a wide array of clinical manifestations that complicate diagnosis, particularly when neurological symptoms are understated. nGD may manifest as the acute neuronopathic type, or GD type 2 (GD2), either prenatally or within the first weeks to months of life, whereas GD type 3 (GD3) symptoms may emerge at any point during childhood or occasionally in adolescence. The clinical presentation encompasses severe systemic involvement to mild visceral disease, often coupled with a spectrum of progressive neurological signs and symptoms such as cognitive impairment, ataxia, seizures, myoclonus, varying degrees of brainstem dysfunction presenting with stridor, apneic episodes, and/or impaired swallowing.

The Expression and Secretion Profile of TRAP5 Isoforms in Gaucher Disease.

Background: Gaucher disease (GD) is caused by glucocerebrosidase (GCase) enzyme deficiency, leading to glycosylceramide (Gb-1) and glucosylsphingosine (Lyso-Gb-1) accumulation. The pathological hallmark for GD is an accumulation of large macrophages called Gaucher cells (GCs) in the liver, spleen, and bone marrow, which are associated with chronic organ enlargement, bone manifestations, and inflammation. Tartrate-resistant acid phosphatase type 5 (TRAP5 protein, gene) has long been a nonspecific biomarker of macrophage/GCs activation; however, the discovery of two isoforms of TRAP5 has expanded its significance.

Biofabrication of anbone model for Gaucher disease.

Gaucher disease (GD), the most prevalent lysosomal disorder, is caused bygene mutations, leading to deficiency of glucocerebrosidase, and accumulation of glycosphingolipids in cells of the mononuclear phagocyte system. While skeletal diseases are the leading cause of morbidity and reduced quality of life in GD, the pathophysiology of bone involvement is not yet fully understood, partly due to lack of relevant human model systems. In this work, we present the first 3D human model of GD using aspiration-assisted freeform bioprinting, which enables a platform tool with a potential for decoding the cellular basis of the developmental bone abnormalities in GD.

Circulated TGF-β1 and VEGF-A as Biomarkers for Fabry Disease-Associated Cardiomyopathy.

Fabry disease (FD) is a lysosomal disorder caused by α-galactosidase A deficiency, resulting in the accumulation of globotriaosylceramide (Gb-3) and its metabolite globotriaosylsphingosine (Lyso-Gb-3). Cardiovascular complications and hypertrophic cardiomyopathy (HCM) are the most frequent manifestations of FD. While an echocardiogram and cardiac MRI are clinical tools to assess cardiac involvement, hypertrophic pattern variations and fibrosis make it crucial to identify biomarkers to predict early cardiac outcomes.

Wnt signaling pathway inhibitors, sclerostin and DKK-1, correlate with pain and bone pathology in patients with Gaucher disease.

Patients with Gaucher disease (GD) have progressive bone involvement that clinically presents with debilitating bone pain, structural bone changes, bone marrow infiltration (BMI), Erlenmeyer (EM) flask deformity, and osteoporosis. Pain is referred by the majority of GD patients and continues to persist despite the type of therapy. The pain in GD is described as chronic deep penetrating pain; however, sometimes, patients experience severe acute pain.

Cellular and biochemical response to chaperone versus substrate reduction therapies in neuropathic Gaucher disease.

Gaucher disease (GD) is caused by deficiency of the lysosomal membrane enzyme glucocerebrosidase (GCase) and the subsequent accumulation of its substrate, glucosylceramide (GC). Mostly missense mutations of the glucocerebrosidase gene (GBA) cause GCase misfolding and inhibition of proper lysosomal trafficking. The accumulated GC leads to lysosomal dysfunction and impairs the autophagy pathway.

TRAP5b and RANKL/OPG Predict Bone Pathology in Patients with Gaucher Disease.

Background And Objective: Bone involvement occurs in 75% of patients with Gaucher disease (GD), and comprises structural changes, debilitating pain, and bone density abnormalities. Osteoporosis is a silent manifestation of GD until a pathologic fracture occurs. Thus, early diagnosis is crucial for identifying high-risk patients in order to prevent irreversible complications.

Selective screening for lysosomal storage disorders in a large cohort of minorities of African descent shows high prevalence rates and novel variants.

Population studies point to regional and ethnicity-specific differences in genetic predisposition for some lysosomal storage disorders (LSDs). The aim of the study was to determine the prevalence of the three treatable forms of lysosomal storage disorders (Gaucher disease [GD], Pompe disease [PD], and Fabry disease [FD]) in a cohort of mostly urban-dwelling individuals of African ancestry, a previously unknown genetic landscape for LSDs. Large-scale selective multistep biochemical and genetic screening was performed in patients seeking healthcare for various health concerns.

Rapid Clathrin-Mediated Uptake of Recombinant α-Gal-A to Lysosome Activates Autophagy.

Enzyme replacement therapy (ERT) with recombinant alpha-galactosidase A (rh-α-Gal A) is the standard treatment for Fabry disease (FD). ERT has shown a significant impact on patients; however, there is still morbidity and mortality in FD, resulting in progressive cardiac, renal, and cerebrovascular pathology. The main pathway for delivery of rh-α-Gal A to lysosome is cation-independent mannose-6-phosphate receptor (CI-M6PR) endocytosis, also known as insulin-like growth factor 2 receptor (IGF2R) endocytosis.

Altered Sphingolipids Metabolism Damaged Mitochondrial Functions: Lessons Learned From Gaucher and Fabry Diseases.

Sphingolipids represent a class of bioactive lipids that modulate the biophysical properties of biological membranes and play a critical role in cell signal transduction. Multiple studies have demonstrated that sphingolipids control crucial cellular functions such as the cell cycle, senescence, autophagy, apoptosis, cell migration, and inflammation. Sphingolipid metabolism is highly compartmentalized within the subcellular locations.

Tissue classification of oncologic esophageal resectates based on hyperspectral data.

Purpose: Esophageal carcinoma is the eighth most common cancer worldwide. Esophageal resection with gastric pull-up is a potentially curative therapeutic option. After this procedure, the specimen is examined by the pathologist to confirm complete removal of the cancer.

Individualized screening for chaperone activity in Gaucher disease using multiple patient derived primary cell lines.

The knowledge of individual response to a therapy, which can be assesed by screening, is essential for the development of therapeutics. Chaperone therapy is based on the ability of small molecules to fold the mutant protein to recover its function. As a novel approach for the treatment of Gaucher disease (GD), ambroxol was recently identified as a chaperone for GD, caused by the pathogenic variants in gene, resulting in lysosomal enzyme glucocerebrosidase (GCase) deficiency.

Impaired autophagic and mitochondrial functions are partially restored by ERT in Gaucher and Fabry diseases.

The major cellular clearance pathway for organelle and unwanted proteins is the autophagy-lysosome pathway (ALP). Lysosomes not only house proteolytic enzymes, but also traffic organelles, sense nutrients, and repair mitochondria. Mitophagy is initiated by damaged mitochondria, which is ultimately degraded by the ALP to compensate for ATP loss.

Involvement of hippocampal angiotensin 1 receptors in anxiety-like behaviour of olfactory bulbectomized rats.

Background: Accumulated evidence suggests that the enhanced brain angiotensin II (Ang II) activity is associated with stress and anxiety. More recent reports demonstrated that Ang II function is elevated in depression, but the role of hippocampal Ang II and its receptors in this state is not well established. The present study investigated the effects of Ang II and losartan (a selective Аng II type 1 receptor antagonist) microinjected into the hippocampal CA1 area on the anxiety-like behavior in rats with a model of depression.

Gaucheromas: When macrophages promote tumor formation and dissemination.

Deficiency of the lysosomal enzyme, β-glucocerebrosidase, and accumulation of its substrate in cells of the reticuloendothelial system affects multiple organ systems in patients with Gaucher disease (GD). Lipid laden macrophages turn into Gaucher cells (GC) which are the pathological characteristic of GD. GC focally accumulate in the liver, spleen and at extraosseous sites to form benign lesions called Gaucheromas.

Nuclear respiratory factor-1 and bioenergetics in tamoxifen-resistant breast cancer cells.

Acquired tamoxifen (TAM) resistance is a significant clinical problem in treating patients with estrogen receptor α (ERα)+ breast cancer. We reported that ERα increases nuclear respiratory factor-1 (NRF-1), which regulates nuclear-encoded mitochondrial gene transcription, in MCF-7 breast cancer cells and NRF-1 knockdown stimulates apoptosis. Whether NRF-1 and target gene expression is altered in endocrine resistant breast cancer cells is unknown.

Persistent immune alterations and comorbidities in splenectomized patients with Gaucher disease.

Gaucher disease (GD) is an autosomal recessive disorder caused by mutations in the gene encoding acid-β-glucosidase, resulting in functional disruptions in degradation of glycosphingolipids and lysosomal accumulation of the substrates. The most frequent clinical presentations of GD are thrombocytopenia, splenomegaly and bone pain. Prior to advent of enzyme replacement therapy, splenectomy was performed for complications of hypersplenism such as severe thrombocytopenia and transfusion dependency.

Clinical and radiographic delineation of Bent Bone Dysplasia-FGFR2 type or Bent Bone Dysplasia with Distinctive Clavicles and Angel-shaped Phalanges.

Bent Bone Dysplasia-FGFR2 type is a relatively recently described bent bone phenotype with diagnostic clinical, radiographic, and molecular characteristics. Here we report on 11 individuals, including the original four patients plus seven new individuals with three longer-term survivors. The prenatal phenotype included stillbirth, bending of the femora, and a high incidence of polyhydramnios, prematurity, and perinatal death in three of 11 patients in the series.

Dehydroepiandrosterone Activation of G-protein-coupled Estrogen Receptor Rapidly Stimulates MicroRNA-21 Transcription in Human Hepatocellular Carcinoma Cells.

Little is known about the regulation of the oncomiR miR-21 in liver. Dehydroepiandrosterone (DHEA) regulates gene expression as a ligand for a G-protein-coupled receptor and as a precursor for steroids that activate nuclear receptor signaling. We report that 10 nm DHEA increases primary miR-21 (pri-miR-21) transcription and mature miR-21 expression in HepG2 cells in a biphasic manner with an initial peak at 1 h followed by a second, sustained response from 3-12 h.

Soy glyceollins regulate transcript abundance in the female mouse brain.

Glyceollins (Glys), produced by soy plants in response to stress, have anti-estrogenic activity in breast and ovarian cancer cell lines in vitro and in vivo. In addition to known anti-estrogenic effects, Gly exhibits mechanisms of action not involving estrogen receptor (ER) signaling. To date, effects of Gly on gene expression in the brain are unknown.

Bioenergetic differences between MCF-7 and T47D breast cancer cells and their regulation by oestradiol and tamoxifen.

Oestrogen receptor α (ERα+) breast tumours rely on mitochondria (mt) to generate ATP. The goal of the present study was to determine how oestradiol (E2) and 4-hydroxytamoxifen (4-OHT) affect cellular bioenergetic function in MCF-7 and T47D ERα+ breast cancer cells in serum-replete compared with dextran-coated charcoal (DCC)-stripped foetal bovine serum (FBS)-containing medium ('serum-starved'). Serum-starvation reduced oxygen consumption rate (OCR), extracellular acidification rate (ECAR), ATP-linked OCR and maximum mt capacity, reflecting lower ATP demand and mt respiration.

Modulatory effect of VIP injected into hippocampal CA1 area on anxiety in olfactory bulbectomized rats.

Vasoactive intestinal peptide (VIP) is a neuropeptide, which is widely distributed in the central nervous system and peripheral tissues, acting both as a neurotransmitter and neuromodulator. Despite its extensive expression in the hippocampus, amygdala and other limbic system structures, the effects of VIP on anxiety and depression have not yet been fully investigated. The aim of the present study was to evaluate the involvement of VIP and VIP receptors in the mechanism of anxiety in rats with a model of depression (bilateral olfactory bulbectomy), using the elevated plus-maze test.

Prenatal and postnatal findings in serpentine fibula polycystic kidney syndrome and a review of the NOTCH2 spectrum disorders.

Serpentine fibula polycystic kidney syndrome (SFPKS; OMIM600330) is a rare skeletal dysplasia with a characteristic phenotype that includes polycystic kidneys, S-shaped fibulas, and abnormal craniofacial features. SFPKS shares features with Alagille (AGS; OMIM) and Hajdu-Cheney (HCS; OMIM10250) syndromes. All three syndromes result from mutations in the gene that encodes NOTCH2, one of the receptors involved in Notch signaling.