@article{18779,
  abstract     = {Unsupervised segmentation in biological and non-biological images is only partially resolved. Segmentation either requires arbitrary thresholds or large teaching datasets. Here, we propose a spatial autocorrelation method based on Local Moran’s <jats:italic>I</jats:italic> coefficient to differentiate signal, background, and noise in any type of image. The method, originally described for geoinformatics, does not require a predefined intensity threshold or teaching algorithm for image segmentation and allows quantitative comparison of samples obtained in different conditions. It utilizes relative intensity as well as spatial information of neighboring elements to select spatially contiguous groups of pixels. We demonstrate that Moran’s method outperforms threshold-based method in both artificially generated as well as in natural images especially when background noise is substantial. This superior performance can be attributed to the exclusion of false positive pixels resulting from isolated, high intensity pixels in high noise conditions. To test the method’s power in real situation, we used high power confocal images of the somatosensory thalamus immunostained for Kv4.2 and Kv4.3 (A-type) voltage-gated potassium channels in mice. Moran’s method identified high-intensity Kv4.2 and Kv4.3 ion channel clusters in the thalamic neuropil. Spatial distribution of these clusters displayed strong correlation with large sensory axon terminals of subcortical origin. The unique association of the special presynaptic terminals and a postsynaptic voltage-gated ion channel cluster was confirmed with electron microscopy. These data demonstrate that Moran’s method is a rapid, simple image segmentation method optimal for variable and high noise conditions.},
  author       = {Dávid, Csaba and Giber, Kristóf and Szigeti, Margit Katalin and Köllő, Mihály and Nusser, Zoltan and Acsady, Laszlo},
  issn         = {2050-084X},
  journal      = {eLife},
  publisher    = {eLife Sciences Publications},
  title        = {{A novel image segmentation method based on spatial autocorrelation identifies A-type potassium channel clusters in the thalamus}},
  doi          = {10.7554/elife.89361},
  volume       = {12},
  year         = {2024},
}

@article{12174,
  abstract     = {Vacuolar-type H+-ATPase (V-ATPase) is a multimeric complex present in a variety of cellular membranes that acts as an ATP-dependent proton pump and plays a key role in pH homeostasis and intracellular signalling pathways. In humans, 22 autosomal genes encode for a redundant set of subunits allowing the composition of diverse V-ATPase complexes with specific properties and expression. Sixteen subunits have been linked to human disease.
Here we describe 26 patients harbouring 20 distinct pathogenic de novo missense ATP6V1A variants, mainly clustering within the ATP synthase α/β family-nucleotide-binding domain. At a mean age of 7 years (extremes: 6 weeks, youngest deceased patient to 22 years, oldest patient) clinical pictures included early lethal encephalopathies with rapidly progressive massive brain atrophy, severe developmental epileptic encephalopathies and static intellectual disability with epilepsy. The first clinical manifestation was early hypotonia, in 70%; 81% developed epilepsy, manifested as developmental epileptic encephalopathies in 58% of the cohort and with infantile spasms in 62%; 63% of developmental epileptic encephalopathies failed to achieve any developmental, communicative or motor skills. Less severe outcomes were observed in 23% of patients who, at a mean age of 10 years and 6 months, exhibited moderate intellectual disability, with independent walking and variable epilepsy. None of the patients developed communicative language. Microcephaly (38%) and amelogenesis imperfecta/enamel dysplasia (42%) were additional clinical features. Brain MRI demonstrated hypomyelination and generalized atrophy in 68%. Atrophy was progressive in all eight individuals undergoing repeated MRIs.</jats:p>
               <jats:p>Fibroblasts of two patients with developmental epileptic encephalopathies showed decreased LAMP1 expression, Lysotracker staining and increased organelle pH, consistent with lysosomal impairment and loss of V-ATPase function. Fibroblasts of two patients with milder disease, exhibited a different phenotype with increased Lysotracker staining, decreased organelle pH and no significant modification in LAMP1 expression. Quantification of substrates for lysosomal enzymes in cellular extracts from four patients revealed discrete accumulation. Transmission electron microscopy of fibroblasts of four patients with variable severity and of induced pluripotent stem cell-derived neurons from two patients with developmental epileptic encephalopathies showed electron-dense inclusions, lipid droplets, osmiophilic material and lamellated membrane structures resembling phospholipids. Quantitative assessment in induced pluripotent stem cell-derived neurons identified significantly smaller lysosomes.
ATP6V1A-related encephalopathy represents a new paradigm among lysosomal disorders. It results from a dysfunctional endo-lysosomal membrane protein causing altered pH homeostasis. Its pathophysiology implies intracellular accumulation of substrates whose composition remains unclear, and a combination of developmental brain abnormalities and neurodegenerative changes established during prenatal and early postanal development, whose severity is variably determined by specific pathogenic variants.},
  author       = {Guerrini, Renzo and Mei, Davide and Szigeti, Margit Katalin and Pepe, Sara and Koenig, Mary Kay and Von Allmen, Gretchen and Cho, Megan T and McDonald, Kimberly and Baker, Janice and Bhambhani, Vikas and Powis, Zöe and Rodan, Lance and Nabbout, Rima and Barcia, Giulia and Rosenfeld, Jill A and Bacino, Carlos A and Mignot, Cyril and Power, Lillian H and Harris, Catharine J and Marjanovic, Dragan and Møller, Rikke S and Hammer, Trine B and Keski Filppula, Riikka and Vieira, Päivi and Hildebrandt, Clara and Sacharow, Stephanie and Maragliano, Luca and Benfenati, Fabio and Lachlan, Katherine and Benneche, Andreas and Petit, Florence and de Sainte Agathe, Jean Madeleine and Hallinan, Barbara and Si, Yue and Wentzensen, Ingrid M and Zou, Fanggeng and Narayanan, Vinodh and Matsumoto, Naomichi and Boncristiano, Alessandra and la Marca, Giancarlo and Kato, Mitsuhiro and Anderson, Kristin and Barba, Carmen and Sturiale, Luisa and Garozzo, Domenico and Bei, Roberto and Masuelli, Laura and Conti, Valerio and Novarino, Gaia and Fassio, Anna},
  issn         = {1460-2156},
  journal      = {Brain},
  keywords     = {Neurology (clinical)},
  number       = {8},
  pages        = {2687--2703},
  publisher    = {Oxford University Press},
  title        = {{Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis}},
  doi          = {10.1093/brain/awac145},
  volume       = {145},
  year         = {2022},
}

@article{6470,
  abstract     = {Investigating neuronal activity using genetically encoded Ca2+ indicators in behaving animals is hampered by inaccuracies in spike inference from fluorescent tracers. Here we combine two‐photon [Ca2+] imaging with cell‐attached recordings, followed by post hoc determination of the expression level of GCaMP6f, to explore how it affects the amplitude, kinetics and temporal summation of somatic [Ca2+] transients in mouse hippocampal pyramidal cells (PCs). The amplitude of unitary [Ca2+] transients (evoked by a single action potential) negatively correlates with GCaMP6f expression, but displays large variability even among PCs with similarly low expression levels. The summation of fluorescence signals is frequency‐dependent, supralinear and also shows remarkable cell‐to‐cell variability. We performed experimental data‐based simulations and found that spike inference error rates using MLspike depend strongly on unitary peak amplitudes and GCaMP6f expression levels. We provide simple methods for estimating the unitary [Ca2+] transients in individual weakly GCaMP6f‐expressing PCs, with which we achieve spike inference error rates of ∼5%. },
  author       = {Éltes, Tímea and Szoboszlay, Miklos and Szigeti, Margit Katalin and Nusser, Zoltan},
  issn         = {1469-7793},
  journal      = {Journal of Physiology},
  number       = {11},
  pages        = {2925–2947},
  publisher    = {Wiley},
  title        = {{Improved spike inference accuracy by estimating the peak amplitude of unitary [Ca2+] transients in weakly GCaMP6f-expressing hippocampal pyramidal cells}},
  doi          = {10.1113/JP277681},
  volume       = {597},
  year         = {2019},
}