A Method for Neuronal Source Identification

Multi-sensor microelectrodes for extracellular action potential recording have significantly improved the quality of in vivo recorded neuronal signals. These microelectrodes have also been instrumental in the localization of neuronal signal sources. However, existing neuron localization methods have been mostly utilized in vivo, where the true neuron location remains unknown. Therefore, these methods could not be experimentally validated. This article presents experimental validation of a method capable of estimating both the location and intensity of an electrical signal source. A four-sensor microelectrode (tetrode) immersed in a saline solution was used to record stimulus patterns at multiple intensity levels generated by a stimulating electrode. The location of the tetrode was varied with respect to the stimulator. The location and intensity of the stimulator were estimated using the Multiple Signal Classification (MUSIC) algorithm, and the results were quantified by comparison to the true values. The localization results, with an accuracy and precision of ~ 10 microns, and ~ 11 microns respectively, imply that MUSIC can resolve individual neuronal sources. Similarly, source intensity estimations indicate that this approach can track changes in signal amplitude over time. Together, these results suggest that MUSIC can be used to characterize neuronal signal sources in vivo.Comment: 14 pages, 5 figure

Automated Detection and Analysis of Depolarization Events in Human Cardiomyocytes using MaDEC

Optical imaging-based methods for assessing the membrane electrophysiology of in vitro human cardiac cells allow for non-invasive temporal assessment of the effect of drugs and other stimuli. Automated methods for detecting and analyzing the depolarization events (DEs) in image-based data allow quantitative assessment of these different treatments. In this study, we use 2-photon microscopy of fluorescent voltage-sensitive dyes (VSDs) to capture the membrane voltage of actively beating human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs). We built a custom and freely available Matlab software, called MaDEC, to detect, quantify, and compare DEs of hiPS-CMs treated with the β-adrenergic drugs, propranolol and isoproterenol. The efficacy of our software is quantified by comparing detection results against manual DE detection by expert analysts, and comparing DE analysis results to known drug-induced electrophysiological effects. The software accurately detected DEs with true positive rates of 98–100% and false positive rates of 1–2%, at signal-to-noise ratios (SNRs) of 5 and above. The MaDEC software was also able to distinguish control DEs from drug-treated DEs both immediately as well as 10 min after drug administration

Granulomatosis with Polyangiitis with Bilateral Facial Palsy and Severe Mixed Hearing Loss

Granulomatosis with polyangiitis is autoimmune and rare disease. It affects many organs, but the most often affected organs are the nose, lungs, and kidneys. It is part of vasculitis and causes an autoimmune attack by an abnormal type of circulating antibody termed ANCAs against small blood vessels. Disease concerns both men and women with a peak age of presentation in the sixth and seven decades. Typically upper and lower respiratory tract and kidneys are involved. Otitis externa, otitis media, or mastoiditis rarely occurs in granulomatosis with polyangiitis. Deafness is the most dangerous aural complication. Histological examination of biopsy is often not specific. A case of GPA with bilateral otitis media, bilateral deafness, and bilateral facial palsy with fatal course is presented

A supervised multi-sensor matched filter for the detection of extracellular action potentials

Multi-sensor extracellular recording takes advantage of several electrode channels to record from multiple neurons at the same time. However, the resulting low signal-to-noise ratio (SNR) combined with biological noise makes signal detection, the first step of any neurophysiological data analysis, difficult. A matched filter was therefore designed to better detect extracellular action potentials (EAPs) from multi-sensor extracellular recordings. The detector was tested on tetrode data from a locust antennal lobe and assessed against three trained analysts. 25 EAPs and noise samples were selected manually from the data and used for training. To reduce complexity, the filter assumed that the underlying noise in the data was spatially white. The detector performed with an average TP and FP rate of 84.62% and 16.63% respectively. This high level of performance indicates the algorithm is suitable for widespread use

Wrodzony hiperinsulinizm — próba optymalizacji diagnostyki i leczenia u polskich pacjentów

  Introduction: Congenital hyperinsulinism of Infancy (CHI) comprises heterogenic defects of insulin secretion with diverse molecular aetiology, histological features, severity of symptoms, and response to pharmacotherapy. The study aimed to establish the first clinical characteristics of Polish patients with CHI and to propose a novel clinical algorithm allowing the prioritisation of genetic and radiology studies, based on patient’s characteristics and response to pharmacotherapy. Material and methods: Thirty-one patients with CHI were recruited from five reference centres in Poland. Clinical and biochemical parameters were statistically evaluated and compared to those of a control group (n = 30). Results: CHI predisposes to increased birth weight (p = 0.004), lower Apgar score (p = 0.004), perinatal complications (74%), and neurological implications (48%). Diagnostic process and therapy were inconsistent. A trial of pharmacotherapy was applied in 21 patients (68%), and diagnostic imaging with 18F-L-DOPA PET was performed in only 3. Eighteen patients (58%) were surgically treated, including 8 infants (44%) aged less than 2 months. Depending on the type of resection, further hypoglycaemia was observed postoperatively in 50% (n = 9) and hyperglycaemia in 39% (n = 7) of cases. Based on foregoing results, a clinical algorithm was proposed. Conclusions: Standardisation of clinical management with the use of pharmacotherapy, genetic screening, and diagnostic imaging will allow the optimisation of therapy and minimisation of treatment complications. (Endokrynol Pol 2015; 66 (4): 322–328)    Wstęp: Wrodzony hiperinsulinizm (CHI) obejmuje heterogenną grupę zaburzeń sekrecji insuliny przez komórki β trzustki i charakteryzuje się zróżnicowaną etiologią molekularną, obrazem histopatologicznym, nasileniem objawów oraz odpowiedzią na leczenie farmakologiczne. Celem pracy było stworzenie charakterystyki klinicznej polskich pacjentów z wrodzonym hiperinsulinizmem oraz podjęcie próby stworzenia algorytmu diagnostyczno-terapeutycznego, umożliwiającego priorytetyzację badań genetycznych i obrazowych w zależności od obrazu klinicznego, wyników badań laboratoryjnych oraz odpowiedzi na leczenie farmakologiczne. Materiał i metody: Do badania włączono 31 pacjentów z rozpoznaną hipoglikemią w przebiegu hiperinsulinizmu z 5 ośrodków w Polsce. Analizę danych klinicznych oraz parametrów biochemicznych pacjentów hipoglikemią odniesiono do 30-osobowej grupy kontrolnej. Wyniki: Pacjenci z CHI charakteryzowali się znacznie wyższą masą urodzeniową (p = 0,004), niższą oceną uzyskaną w okołoporodowej skali Apgar (p = 0,004), częstszymi komplikacjami okołoporodowymi (74%) oraz powikłaniami neurologicznymi (48%). Przeprowadzona w badanej grupie diagnostyka była niespójna. U 21 pacjentów (68%) włączono leczenie za pomocą Diazoksydu, a u 3 pacjentów (9,7%) wykonano diagnostykę obrazową przy użyciu 18F-L-DOPA PET. Wśród 18 (58%) pacjentów leczonych chirurgicznie u 8 (44%) resekcję wykonano w wieku poniżej 2. miesiąca życia. Pooperacyjnie w zależności od typu wykonanej operacji obserwowano hipoglikemię u 50% (n = 9), a hiperglikemię u 39% (n = 7). Na podstawie uzyskanych wyników zaproponowano pierwszy w Polsce algorytm diagnostyczno- terapeutyczny. Wnioski: Ujednolicenie schematu postępowania diagnostycznego-terapeutycznego z wykorzystaniem wszystkich dostępnych metod umożliwi zapobieganie kolejnym epizodom choroby, oraz zminimalizuje komplikacje wynikające z leczenia. (Endokrynol Pol 2015; 66 (4): 322–328)

Impaired dynamin 2 function leads to increased AP-1 transcriptional activity through the JNK/c-Jun pathway

Activation of AP-1 transcription factors, composed of the Jun and Fos proteins, regulates cellular fates, such as proliferation, differentiation or apoptosis. Among other stimuli, the AP-1 pathway can be initiated by extracellular ligands, such as growth factors or cytokines, which undergo internalization in complex with their receptors. Endocytosis has been implicated in the regulation of several signaling pathways; however its possible impact on AP-1 signaling remains unknown. Here we show that inhibition of dynamin 2 (Dyn2), a major regulator of endocytic internalization, strongly stimulates the AP-1 pathway. Specifically, expression of a dominant-negative Dyn2 K44A mutant increases the total levels of c-Jun, its phosphorylation on Ser63/73 and transcription of AP-1 target genes. Interestingly, DNM2 mutations implicated in human neurological disorders exhibit similar effects on AP-1 signaling. Mechanistically, Dyn2 K44A induces AP-1 by increasing phosphorylation of several receptor tyrosine kinases. Their activation is required to initiate a Src- and JNK-dependent signaling cascade converging on c-Jun and stimulating expression of AP-1 target genes. Cumulatively, our data uncover a link between the Dyn2 function and JNK signaling which leads to AP-1 induction

We Do Not Like It: A Likert-Type Scale Survey on the Attitudes of a Young Population towards the Transhumanistic Theory of Education

Transhumanists assume that future education may be purely based on technological stimulation. The question is: Do potential clients of education “like” such vision? In order to check this, we asked over one thousand two hundred young Poles to evaluate their identification with the transhumanistic theory of education. The results are quite surprising: its show that they disagree with the assumptions of this theory, while they rather agree with the postulates of more traditional (and no technology-based) concepts of education