AIMS: Sinonasal adenosquamous carcinoma (ASC) is a rare tumour classified as a variant of squamous cell carcinoma, exhibiting both squamous and glandular differentiation. ASC has a poorer prognosis compared to sinonasal mucoepidermoid carcinoma (MEC), another uncommon tumour in this region. ASC is believed to originate from metaplastic squamous epithelium, though it may also arise from respiratory epithelium in respiratory epithelial adenomatoid hamartoma (REAH) or seromucinous glands in seromucinous hamartoma (SH). METHODS AND RESULTS: Five cases of sinonasal ASC were retrieved from our registry. Initially, they were classified as sinonasal MEC (n = 3), ASC (n = 2), and carcinoma ex REAH (n = 1). All cases showed adenosquamous malignant proliferation beneath the surface respiratory epithelium with occasional squamous metaplasia, except for one case that showed dysplasia. The respiratory epithelium exhibited an inverted growth pattern consistent with REAH/SH, and displayed atypical sinonasal glands (ASGSH) arising within seromucinous hamartoma. Next-generation sequencing (NGS) revealed multiple pathogenic mutations in two cases, and in case 4 GGA2::PRKCB and EYA2::SERINC3 gene fusions. One case was positive for high-risk HPV. None of the cases exhibited CRTC1/3::MAML2 gene fusion. CONCLUSION: The connection between ASGSH and ASC has not been described in the literature. There is a growing need for additional studies on the morphological, immunohistochemical, and genetic aspects of these tumours. SH/REAH may serve as precursor lesions in the progression of atypical sinonasal glands to malignancy, and their role in tumour development deserves further investigation.

• MeSH
• adenoskvamózní karcinom * patologie   genetika   MeSH
• dospělí MeSH
• hamartom * patologie   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory vedlejších dutin nosních patologie   genetika   MeSH
• respirační sliznice patologie   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: Docetaxel resistance is a significant obstacle in the treatment of prostate cancer (PCa), resulting in unfavorable patient prognoses. Intratumoral heterogeneity, often associated with epithelial-to-mesenchymal transition (EMT), has previously emerged as a phenomenon that facilitates adaptation to various stimuli, thus promoting cancer cell diversity and eventually resistance to chemotherapy, including docetaxel. Hence, understanding intratumoral heterogeneity is essential for better patient prognosis and the development of personalized treatment strategies. METHODS: To address this, we employed a high-throughput single-cell flow cytometry approach to identify a specific surface fingerprint associated with docetaxel-resistance in PCa cells and complemented it with proteomic analysis of extracellular vesicles. We further validated selected antigens using docetaxel-resistant patient-derived xenografts in vivo and probed primary PCa specimens to interrogate of their surface fingerprint. RESULTS: Our approaches revealed a 6-molecule surface fingerprint linked to docetaxel resistance in primary PCa specimens. We observed consistent overexpression of CD95 (FAS/APO-1), and SSEA-4 surface antigens in both in vitro and in vivo docetaxel-resistant models, which was also observed in a cell subpopulation of primary PCa tumors exhibiting EMT features. Furthermore, CD95, along with the essential enzymes involved in SSEA-4 synthesis, ST3GAL1, and ST3GAL2, displayed a significant increase in patients with PCa undergoing docetaxel-based therapy, correlating with poor survival outcomes. CONCLUSION: In summary, we demonstrate that the identified 6-molecule surface fingerprint associated with docetaxel resistance pre-exists in a subpopulation of primary PCa tumors before docetaxel treatment. Thus, this fingerprint warrants further validation as a promising predictive tool for docetaxel resistance in PCa patients prior to therapy initiation.

• MeSH
• chemorezistence * MeSH
• docetaxel * farmakologie   terapeutické užití   MeSH
• epitelo-mezenchymální tranzice účinky léků   MeSH
• lidé MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádory prostaty * patologie   farmakoterapie   metabolismus   MeSH
• protinádorové látky farmakologie   terapeutické užití   MeSH
• xenogenní modely - testy protinádorové aktivity MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Glioblastomas are aggressive brain tumors for which effective therapy is still lacking, resulting in dismal survival rates. These tumors display significant phenotypic plasticity, harboring diverse cell populations ranging from tumor core cells to dispersed, highly invasive cells. Neuron navigator 3 (NAV3), a microtubule-associated protein affecting microtubule growth and dynamics, is downregulated in various cancers, including glioblastoma, and has thus been considered a tumor suppressor. In this study, we challenge this designation and unveil distinct expression patterns of NAV3 across different invasion phenotypes. Using glioblastoma cell lines and patient-derived glioma stem-like cell cultures, we disclose an upregulation of NAV3 in invading glioblastoma cells, contrasting with its lower expression in cells residing in tumor spheroid cores. Furthermore, we establish an association between low and high NAV3 expression and the amoeboid and mesenchymal invasive phenotype, respectively, and demonstrate that overexpression of NAV3 directly stimulates glioblastoma invasive behavior in both 2D and 3D environments. Consistently, we observed increased NAV3 expression in cells migrating along blood vessels in mouse xenografts. Overall, our results shed light on the role of NAV3 in glioblastoma invasion, providing insights into this lethal aspect of glioblastoma behavior.

• MeSH
• fenotyp * MeSH
• glioblastom * patologie   genetika   metabolismus   MeSH
• invazivní růst nádoru * genetika   MeSH
• lidé MeSH
• membránové proteiny MeSH
• mikrotubuly metabolismus   MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádory mozku * patologie   genetika   metabolismus   MeSH
• pohyb buněk genetika   fyziologie   MeSH
• proteiny nervové tkáně metabolismus   genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Starting point: Cervical dystonia is a common form of focal dystonia, resulting in neck pain and the development of asymmetric neck and head postures. These abnormal postures contribute to muscular impairment, muscle imbalances, and, as a result, alteration in movement patterns. This study aimed to compare the asymmetry of cervical muscle activation pattern during cervical flexion movements between individuals with cervical dystonia and healthy young subjects. Methods: Eight individuals with cervical dystonia and eight healthy participants participated in this study. We recorded muscle activation from five pairs of cervical muscles (sternocleidomastoid, scalene, trapezius, suprahyoid, and infrahyoid) using surface electromyography. Normalized cross-correlation was used to analyze the symmetry of bilateral muscle activation. Results: The results showed significant differences in muscle activation symmetry between the cervical dystonia group and healthy subjects. Notably, patients with cervical dystonia exhibited less symmetric activation in the trapezius and sternocleidomastoid muscles compared to healthy controls (p < 0.01 and p < 0.05, respectively). Additionally, the trapezius muscle on the dystonic side lacked coordination with other cervical muscles, unlike in healthy individuals who displayed better coordination. Conclusions: These findings underline the challenges faced by individuals with cervical dystonia in achieving symmetric activation and coordination of cervical muscles. Evaluating cervical muscle activation symmetry may be a valuable approach for assessing motor impairments in these patients.

Mitochondria are key to cellular energetics, metabolism, and signaling. Their dysfunction is linked to devastating diseases, including mitochondrial disorders, diabetes, neurodegenerative diseases, cardiac disorders, and cancer. Here, we present a knockout mouse model lacking the complex IV assembly factor SMIM20/MITRAC7. SMIM20-/- mice display cardiac pathology with reduced heart weight and cardiac output. Heart mitochondria present with reduced levels of complex IV associated with increased complex I activity, have altered fatty acid oxidation, and display elevated levels of ROS production. Interestingly, mutant mouse ventricular myocytes show unphysiological Ca2+ handling, which can be attributed to the increase in mitochondrial ROS production. Our study presents an example of a tissue-specific phenotype in the context of OXPHOS dysfunction. Moreover, our data suggest a link between complex IV dysfunction and Ca2+ handling at the endoplasmic reticulum through ROS signaling.

• MeSH
• endoplazmatické retikulum metabolismus   MeSH
• kardiomyocyty metabolismus   MeSH
• membránové proteiny * metabolismus   genetika   MeSH
• mitochondriální proteiny * metabolismus   genetika   MeSH
• myokard * metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• oxidativní fosforylace MeSH
• proteiny dánia pruhovaného MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• respirační komplex IV * metabolismus   MeSH
• srdeční mitochondrie metabolismus   MeSH
• vápník metabolismus   MeSH
• vápníková signalizace * MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Despite the significance of neck muscles in musculoskeletal disorders, their microscopic anatomy remains poorly characterized. This study examined the splenius capitis muscle, focusing on its fiber-type composition, fiber size, and capillary network characteristics. For comparison and validation, the vastus lateralis muscle was also analyzed. Muscle samples from 13 young male subjects (mean age ± SD: 35.7 ± 8.6 years) were collected within 24-h post-mortem during autopsy. Myosin heavy chain (MyHC) isoform expression was characterized immunohistochemically in 10 μm sections, while the capillary network architecture was assessed in 100 μm sections. Immunofluorescence staining, confocal microscopy, and 3D image analysis were employed to quantify capillary tortuosity, anisotropy, branch density (Br dens), and the length of capillaries per muscle volume (LV), per muscle fiber length (LL), per fiber surface area (LS), and per fiber volume (LVf). Compared to the vastus lateralis muscle, the splenius capitis muscle had a higher percentage of type 1 fibers (51.2% vs 39.7%), fewer type 2a fibers (16.2% vs 31.4%), and smaller fiber diameters (35.5-40.9 μm vs 47-56.1 μm). It also displayed lower Br dens (P = 0.0069), higher anisotropy (P = 0.0004), and lower LL (P < 0.0001) but higher LVf (P = 0.0486). In the splenius capitis muscle, body mass index (BMI) negatively correlated with LV (P = 0.0155), LS (P = 0.0091), LVf (P = 0.0137), and anisotropy (P = 0.0425), and positively correlated with tortuosity (P = 0.0473), indicating a reduction in the capillary network. In the vastus lateralis muscle, only LV (P = 0.0161) decreased with high BMI. This study characterized the fiber-type composition, fiber size, and 3D capillary network of the splenius capitis muscle, establishing a baseline for investigations into pathological muscle alterations.

• MeSH
• dospělí MeSH
• kapiláry * metabolismus   MeSH
• kosterní svalová vlákna * metabolismus   MeSH
• krční svaly * krevní zásobení   metabolismus   MeSH
• lidé MeSH
• těžké řetězce myosinu metabolismus   MeSH
• zobrazování trojrozměrné MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: To document the expression of apical-basal polarity (ABP) determinants in the mouse corneal epithelium (CE) and elucidate the functions of Pard3 in establishment and maintenance of ABP, stratification, homeostasis, and barrier function in the CE. METHODS: Pard3Δ/ΔC mice (Pard3LoxP/LoxP; Aldh3A1-Cre/+) with cornea-specific Pard3 ablation were generated by breeding Aldh3A1-Cre/+ with Pard3LoxP/LoxP mice. The control (Aldh3A1-Cre/+ or Pard3LoxP/LoxP alone) and Pard3Δ/ΔC corneal histology, ocular surface properties, barrier function, and actin cytoskeleton were assessed by Haematoxylin and Eosin staining of paraformaldehyde-fixed, paraffin-embedded tissues, scanning electron microscopy, fluorescein staining, and phalloidin staining, respectively. The expression of specific markers of interest was evaluated by qRT-PCR, immunoblots and immunofluorescent staining. RESULTS: Dynamic changes were observed in the expression and localization of ABP determinants as the CE stratified and matured between post-natal day 5 (PN5) and PN52. Adult Pard3Δ/ΔC CE contained fewer cell layers with rounded basal cells, and loosely adherent superficial cells lacking microplicae. Adult Pard3Δ/ΔC CE also displayed impaired barrier function with decreased expression of tight junction, adherens junction, and desmosome components, disrupted actin cytoskeletal organization, increased proliferation, and upregulation of transcription factors that drive epithelial-mesenchymal transition (EMT). CONCLUSIONS: Disruption of ABP in Pard3Δ/ΔC CE, altered expression of cell junction complex components and disorganized actin cytoskeleton, increased cell proliferation, and upregulated EMT transcription factors suggest that the ABP-determinant Pard3 promotes CE features while suppressing mesenchymal cell fate. Collectively, these results elucidate that Pard3-mediated ABP is essential for CE stratification, homeostasis and barrier function.

• MeSH
• adaptorové proteiny signální transdukční * MeSH
• cytoskelet * metabolismus   MeSH
• homeostáza fyziologie   MeSH
• mikroskopie elektronová rastrovací MeSH
• myši MeSH
• polarita buněk * fyziologie   MeSH
• rohovkový epitel * metabolismus   ultrastruktura   MeSH
• těsný spoj * metabolismus   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: The clinical diversity of schizophrenia is reflected by structural brain variability. It remains unclear how this variability manifests across different gray and white matter features. In this meta- and mega-analysis, the authors investigated how brain heterogeneity in schizophrenia is distributed across multimodal structural indicators. METHODS: The authors used the ENIGMA dataset of MRI-based brain measures from 22 international sites with up to 6,037 individuals for a given brain measure. Variability and mean values of cortical thickness, cortical surface area, cortical folding index, subcortical volume, and fractional anisotropy were examined in individuals with schizophrenia and healthy control subjects. RESULTS: Individuals with schizophrenia showed greater variability in cortical thickness, cortical surface area, subcortical volume, and fractional anisotropy within the frontotemporal and subcortical network. This increased structural variability was mainly associated with psychopathological symptom domains, and the schizophrenia group frequently displayed lower mean values in the respective structural measures. Unexpectedly, folding patterns were more uniform in individuals with schizophrenia, particularly in the right caudal anterior cingulate region. The mean folding values of the right caudal anterior cingulate region did not differ between the schizophrenia and healthy control groups, and folding patterns in this region were not associated with disease-related parameters. CONCLUSIONS: In patients with schizophrenia, uniform folding patterns in the right caudal anterior cingulate region contrasted with the multimodal variability in the frontotemporal and subcortical network. While variability in the frontotemporal and subcortical network was associated with disease-related diversity, uniform folding may indicate a less flexible interplay between genetic and environmental factors during neurodevelopment.

• MeSH
• anizotropie MeSH
• bílá hmota patologie   diagnostické zobrazování   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek * patologie   diagnostické zobrazování   MeSH
• schizofrenie * patologie   diagnostické zobrazování   MeSH
• šedá hmota patologie   diagnostické zobrazování   MeSH
• zobrazování difuzních tenzorů MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH

The RNA chaperone Hfq plays crucial roles in bacterial gene expression and is a major facilitator of small regulatory RNA (sRNA) action. The toroidal architecture of the Hfq hexamer presents three well-characterized surfaces that allow it to bind sRNAs to stabilize them and engage target transcripts. Hfq-interacting sRNAs are categorized into two classes based on the surfaces they use to bind Hfq. By characterizing a systematic alanine mutant library of Hfq to identify amino acid residues that impact survival of Escherichia coli experiencing nitrogen (N) starvation, we corroborated the important role of the three RNA-binding surfaces for Hfq function. We uncovered two, previously uncharacterized, conserved residues, V22 and G34, in the hydrophobic core of Hfq, to have a profound impact on Hfq's RNA-binding activity in vivo. Transcriptome-scale analysis revealed that V22A and G34A Hfq mutants cause widespread destabilization of both sRNA classes, to the same extent as seen in bacteria devoid of Hfq. However, the alanine substitutions at these residues resulted in only modest alteration in stability and structure of Hfq. We propose that V22 and G34 have impact on Hfq function, especially critical under cellular conditions when there is an increased demand for Hfq, such as N starvation.

• MeSH
• bakteriální RNA * metabolismus   genetika   chemie   MeSH
• dusík metabolismus   MeSH
• Escherichia coli * genetika   metabolismus   MeSH
• hydrofobní a hydrofilní interakce * MeSH
• konzervovaná sekvence MeSH
• malá nekódující RNA * metabolismus   genetika   chemie   MeSH
• mutace MeSH
• protein hostitelského faktoru 1 * metabolismus   genetika   chemie   MeSH
• proteiny z Escherichia coli * metabolismus   genetika   chemie   MeSH
• regulace genové exprese u bakterií MeSH
• stabilita RNA * genetika   MeSH
• stanovení celkové genové exprese MeSH
• transkriptom genetika   MeSH
• vazba proteinů MeSH
• Publikační typ
• časopisecké články MeSH

Single-cell RNA sequencing (scRNA-seq) methods are widely used in life sciences, including immunology. Typical scRNA-seq analysis pipelines quantify the abundance of particular transcripts without accounting for alternative splicing. However, a well-established pan-leukocyte surface marker, CD45, encoded by the PTPRC gene, presents alternatively spliced variants that define different immune cell subsets. Information about some of the splicing patterns in particular cells in the scRNA-seq data can be obtained using isotype-specific DNA oligo-tagged anti-CD45 antibodies. However, this requires generation of an additional sequencing DNA library. Here, we present IDEIS, an easy-to-use software for CD45 isoform quantification that uses single-cell transcriptomic data as the input. We showed that IDEIS accurately identifies canonical human CD45 isoforms in datasets generated by 10× Genomics 5' sequencing assays. Moreover, we used IDEIS to determine the specificity of the Ptprc splicing pattern in mouse leukocyte subsets.

• MeSH
• alternativní sestřih MeSH
• analýza jednotlivých buněk metody   MeSH
• antigeny CD45 * genetika   metabolismus   MeSH
• leukocyty metabolismus   imunologie   MeSH
• lidé MeSH
• myši MeSH
• protein - isoformy genetika   MeSH
• sekvenční analýza RNA metody   MeSH
• software * MeSH
• stanovení celkové genové exprese metody   MeSH
• transkriptom MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH