Axonal Odorant Receptors Mediate Axon Targeting

In mammals, odorant receptors not only detect odors but also define the target in the olfactory bulb, where sensory neurons project to give rise to the sensory map. The odorant receptor is expressed at the cilia, where it binds odorants, and at the axon terminal. The mechanism of activation and function of the odorant receptor at the axon terminal is, however, still unknown. Here, we identify phosphatidylethanolamine- binding protein 1 as a putative ligand that activates the odorant receptor at the axon terminal and affects the turning behavior of sensory axons.Genetic ablation of phosphatidylethanolamine-binding protein 1 in mice results in a strongly disturbed olfactory sensory map. Our data suggest that the odorant receptor at the axon terminal of olfactory neurons acts as an axon guidance cue that responds to molecules originating in the olfactory bulb. The dual function of the odorant receptor links specificity of odor perception and axon targeting

Should We Continue to Measure Endometrial Thickness in Modern-Day Medicine? The Effect on Live Birth Rates and Birth Weight

The evaluation of endometrial thickness (EMT) is still part of standard cycle monitoring during IVF, despite the lack of robust evidence of any value of this measurement to predict little revalidation in contemporary medical practice; other tools, however, such as endocrine profile monitoring, have become increasingly popular. The aim of this study was to reassess whether EMT affects the outcome of a fresh embryo transfer in modern-day medicine, using a retrospective, single-centre cohort of 3350 IVF cycles (2827 women) carried out between 2010 and 2014. In the multivariate regression analysis, EMT was non-linearly associated with live birth, with live birth rates being the lowest with an EMT less than 7.0 mm (21.6%; P < 0.001) and then between 7.0 mm and 9.0 mm (30.2%; P = 0.008). An EMT less than 7.0 mm was also associated with a decrease in neonatal birthweight z-scores (-0.40; 95% CI -0.69 to -0.12). In conclusion, these results reaffirm the use of EMT as a potential prognostic tool for live birth rates and neonatal birthweight in contemporary IVF, namely when considered together with other ovarian stimulation monitoring methods, such as the late-follicular endocrine profile.info:eu-repo/semantics/publishedVersio

Human iPSC-derived astrocytes transplanted into the mouse brain undergo morphological changes in response to amyloid-beta plaques

BACKGROUND: Increasing evidence for a direct contribution of astrocytes to neuroinflammatory and neurodegenerative processes causing Alzheimer’s disease comes from molecular and functional studies in rodent models. However, these models may not fully recapitulate human disease as human and rodent astrocytes differ considerably in morphology, functionality, and gene expression. RESULTS: To address these challenges, we established an approach to study human astrocytes within the mouse brain by transplanting human induced pluripotent stem cell (hiPSC)-derived astrocyte progenitors into neonatal brains. Xenografted hiPSC-derived astrocyte progenitors differentiated into astrocytes that integrated functionally within the mouse host brain and matured in a cell-autonomous way retaining human-specific morphologies, unique features, and physiological properties. In Alzheimer´s chimeric brains, transplanted hiPSC-derived astrocytes responded to the presence of amyloid plaques undergoing morphological changes that seemed independent of the APOE allelic background. CONCLUSIONS: In sum, we describe here a promising approach that consist of transplanting patient-derived and genetically modified astrocytes into the mouse brain to study human astrocyte pathophysiology in the context of Alzheimer´s disease

Correlation between Pathologic Complete Response in the Breast and Absence of Axillary Lymph Node Metastases after Neoadjuvant Systemic Therapy

Objective:The aim was to investigate whether pathologic complete response (PCR) in the breast is correlated with absence of axillary lymph node metastases at final pathology (ypN0) in patients treated with neoadjuvant systemic therapy (NST) for different breast cancer subtypes.Background:Pathologic complete response rates have improved on account of more effective systemic treatment regimens. Promising results in feasibility trials with percutaneous image-guided tissue sampling for the identification of breast PCR after NST raise the question whether breast surgery is a redundant procedure. Thereby, the need for axillary surgery should be reconsidered as well.Methods:Patients diagnosed with cT1-3N0-1 breast cancer and treated with NST, followed by surgery between 2010 and 2016, were selected from the Netherlands Cancer Registry. Patients were compared according to the pa

Spherical harmonic decomposition applied to spatial-temporal analysis of human high-density EEG

We demonstrate an application of spherical harmonic decomposition to analysis of the human electroencephalogram (EEG). We implement two methods and discuss issues specific to analysis of hemispherical, irregularly sampled data. Performance of the methods and spatial sampling requirements are quantified using simulated data. The analysis is applied to experimental EEG data, confirming earlier reports of an approximate frequency-wavenumber relationship in some bands.Comment: 12 pages, 8 figures, submitted to Phys. Rev. E, uses APS RevTeX style

Tetraspanin 6: a pivotal protein of the multiple vesicular body determining exosome release and lysosomal degradation of amyloid precursor protein fragments

BACKGROUND: The mechanisms behind Aβ-peptide accumulation in non-familial Alzheimer’s disease (AD) remain elusive. Proteins of the tetraspanin family modulate Aβ production by interacting to γ-secretase. METHODS: We searched for tetraspanins with altered expression in AD brains. The function of the selected tetraspanin was studied in vitro and the physiological relevance of our findings was confirmed in vivo. RESULTS: Tetraspanin-6 (TSPAN6) is increased in AD brains and overexpression in cells exerts paradoxical effects on Amyloid Precursor Protein (APP) metabolism, increasing APP-C-terminal fragments (APP-CTF) and Aβ levels at the same time. TSPAN6 affects autophagosome-lysosomal fusion slowing down the degradation of APP-CTF. TSPAN6 recruits also the cytosolic, exosome-forming adaptor syntenin which increases secretion of exosomes that contain APP-CTF. CONCLUSIONS: TSPAN6 is a key player in the bifurcation between lysosomal-dependent degradation and exosome mediated secretion of APP-CTF. This corroborates the central role of the autophagosomal/lysosomal pathway in APP metabolism and shows that TSPAN6 is a crucial player in APP-CTF turnover