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Humans learn from a lot of information sources to make decisions. Once this information is learned in the brain, spatio-temporal associations are made, connecting all these sources (variables) in space and time represented as brain connectivity. In reality, to make a decision, we usually have only part of the information, either as a limited number of variables, limited time to make the decision, or both. The brain functions as a spatio-temporal associative memory. Inspired by the ability of the human brain, a brain-inspired spatio-temporal associative memory was proposed earlier that utilized the NeuCube brain-inspired spiking neural network framework. Here we applied the STAM framework to develop STAM for neuroimaging data, on the cases of EEG and fMRI, resulting in STAM-EEG and STAM-fMRI. This paper showed that once a NeuCube STAM classification model was trained on a complete spatio-temporal EEG or fMRI data, it could be recalled using only part of the time series, or/and only part of the used variables. We evaluated both temporal and spatial association and generalization accuracy accordingly. This was a pilot study that opens the field for the development of classification systems on other neuroimaging data, such as longitudinal MRI data, trained on complete data but recalled on partial data. Future research includes STAM that will work on data, collected across different settings, in different labs and clinics, that may vary in terms of the variables and time of data collection, along with other parameters. The proposed STAM will be further investigated for early diagnosis and prognosis of brain conditions and for diagnostic/prognostic marker discovery. [ABSTRACT FROM AUTHOR]

The lack of airspace capacity poses a significant challenge for a sustainable air transport system, particularly in scenarios of future growing demand. Air traffic management digitalization opens pathways for innovative and efficient solutions to tackle existing inefficiencies arising from spatially fragmented airspace. While research has focused on digitalized ATM services to improve airspace capacity, synergies among adjacent sectors to utilize latent capacity remain unexplored. Using a sector network model, in this study, we analyze spatiotemporal sector interdependencies, quantify time-stamp topological interdependencies, and evaluate capacity enhancement possibilities for sectors unable to meet dynamic demand. The occupancy count dynamic evolution and poor correlation among the over-loaded sectors with the occupancy count of its adjacent sectors provide opportunities for a short-term ATM mechanism, ensuring sector-level capacity invulnerability and enhancing airspace capacity at the network level. A computational experiment using real data from the European airspace is carried out to illustrate and validate this innovative solution. [ABSTRACT FROM AUTHOR]

Stimulator of interferon genes (STING) mediates the innate immune response against damaged endogenous double‐strand DNA and exogenous virus infection. The location of STING is critical to the accurate control of defence signalling pathways. Recently, the effects of extracellular vesicles (EVs) in the regulation of innate immune signalling have been reported. Nevertheless, the particular roles played by STING in EVs and the related mechanisms have remained largely unknown. Herein, we report that when STING was activated in cells, EVs derived from these cells carried STING oligomers. Signal transducing adapter molecule 1 (STAM) was found to be a STING transporter that directly interacted with STING and facilitated STING transport into EVs. Importantly, the translocation of STING into EVs was a mechanism by which STING was degraded, suppressing the innate immune response. In summary, we elucidated the mechanism and function of the translocation of STING into EVs, adding to the understanding of STING activity regulation. [ABSTRACT FROM AUTHOR]

Objective: The objective was to assess Potsic, EAONO/JOS, STAMCO, and ChOLE cholesteatoma staging systems in a large homogenous pediatric cohort with long-term follow-up and propose an evidence-based improved version., Study Design: Cohort study., Setting: Retrospective study in a tertiary referral center., Methods: Children with congenital or acquired cholesteatoma who underwent surgery between 2008 and 2015 and had a minimum of five years follow-up were included. ROC areas under curve (AUCs) were performed for the residual disease proportion, total number of surgeries, hearing, and C-index for recurrence proportion at the last follow-up., Results: Data from 271 ears with cholesteatoma were collected. Mean age at diagnosis was 7.9 years and 77 (28%) were congenital. Almost all patients (99%) had a canal wall up approach. The mean follow-up was 97.8 months. The Potsic classification, initially designed for congenital cholesteatoma, had the highest AUCs for residual disease rate and for number of surgeries outcomes (respectively 0.73 [0.67-0.78] and 0.71 [0.66-0.77]). For recurrence rate, all the classifications' C-index were low (<0.7). For postoperative hearing, STAMCO ossicular subscore had the highest AUC (0.73 [0.67-0.79]). The Mod-Pot staging system (modified Potsic), including stapes superstructure status and anterior epitympanum or supratubal involvement, improved the Potsic performance especially for postoperative hearing with AUC 0.73 [0.67-0.80], p < 0.001., Conclusion: The Potsic, ChOLE, EAONO/JOS, and STAMCO cholesteatoma classifications may be used in children, but in this specific population, their contribution remains limited to predict outcome. The Mod-Pot classification improved the performance of pediatric cholesteatoma classification while remaining simple and intuitive., Level of Evidence: 3 Laryngoscope, 135:908-919, 2025., (© 2024 The Author(s). The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

The lack of airspace capacity poses a significant challenge for a sustainable air transport system, particularly in scenarios of future growing demand. Air traffic management digitalization opens pathways for innovative and efficient solutions to tackle existing inefficiencies arising from spatially fragmented airspace. While research has focused on digitalized ATM services to improve airspace capacity, synergies among adjacent sectors to utilize latent capacity remain unexplored. Using a sector network model, in this study, we analyze spatiotemporal sector interdependencies, quantify time-stamp topological interdependencies, and evaluate capacity enhancement possibilities for sectors unable to meet dynamic demand. The occupancy count dynamic evolution and poor correlation among the over-loaded sectors with the occupancy count of its adjacent sectors provide opportunities for a short-term ATM mechanism, ensuring sector-level capacity invulnerability and enhancing airspace capacity at the network level. A computational experiment using real data from the European airspace is carried out to illustrate and validate this innovative solution.

Background: This study focuses on the hearing threshold for bone conduction (BC) after middle-ear surgery. Methods: A total of 92 patients (120 ears) were treated for newly diagnosed chronic otitis media with cholesteatoma (2013–2018). BC was examined at frequencies of 0.5, 1, 2, and 4 kHz prior to and 1 year after surgery. STAM classification for cholesteatoma location, EAONO/JOS for stage, and surgery according to SAMEO-ATO classification were applied. The bone conduction threshold was compared for individual frequencies in patients with occurrence/absence of cholesteatoma in different locations. Results: For the occurrence of cholesteatoma in the attic (A), a statistically significant difference was found at 4 kHz (p < 0.001), in the supratubal recess (S1) at 4 kHz (p = 0.003), and for the mastoid (M) at 0.5 kHz (p = 0.024), at 1 kHz (p = 0.032), and at 2 kHz (p = 0.039). Conclusions: Cholesteatoma location can influence the post-operative hearing threshold for bone conduction. [ABSTRACT FROM AUTHOR]

Purpose: The term "pectoralis minor syndrome" refers to this constellation of symptoms that can occur when the pectoralis minor (Pm) is shortened and contracted. Release of the tendon of the Pm from the coracoid has been reported to provide substantial clinical improvement to patients presenting with pectoralis minor syndrome. The purpose of this study was (1) to describe the technique for endoscopic release of pectoralis minor tendon at the subdeltoid space, (2) to classify the pectoralis minor syndrome according to its severity and (3) and to report the short-term outcomes of this procedure in a consecutive series of patients diagnosed with pectoralis minor syndrome. Methods: Endoscopic release of the pectoralis minor tendon was performed in a series of 10 patients presenting with pectoralis minor syndrome. There were six females and four males with a median age at the time of surgery of 42 (range from 20 to 58) years. Four shoulders were categorized as grade I (scapular dyskinesis), and six as grade II (intermittent brachial plexopathy). Shoulders were evaluated for pain, motion, satisfaction, subjective shoulder value (SSV), quick-DASH, ASES score, and complications. The mean follow-up time was 19 (range, 6 to 49) months. Results: Arthroscopic release of the tendon of the Pm led to substantial resolution of pectoralis minor syndrome symptoms in all but one shoulder, which was considered a failure. Preoperatively, the median VAS for pain was 8.5 (range, 7–10) and the mean SSV was 20% (range, 10% - 50%). At most recent follow-up the mean VAS for pain was 1 (range, 0–6) and the mean SSV 80% (range, 50% - 90%). Before surgery, mean ASES and quick-DASH scores were 19.1 (range, 10–41.6) and 83.1 (range, 71 and 95.5) points respectively. At most recent follow-up, mean ASES and quick-DASH scores were 80.1 (range, 40–100) and 19.3 (range, 2.3–68) points respectively. No surgical complications occurred in any of the shoulder included in this study. Conclusions: Endoscopic release of the tendon of the pectoralis minor from the coracoid improves pain, function and patient reported outcomes in the majority of patients presenting with the diagnosis of isolated pectoralis minor syndrome. [ABSTRACT FROM AUTHOR]

Biallelic pathogenic variants in TBCK cause encephaloneuropathy, infantile hypotonia with psychomotor retardation, and characteristic facies 3 (IHPRF3). The molecular mechanisms underlying its neuronal phenotype are largely unexplored. In this study, we reported two sisters, who harbored biallelic variants in TBCK and met diagnostic criteria for IHPRF3. We provided evidence that TBCK may play an important role in the early secretory pathway in neuroprogenitor cells (iNPC) differentiated from induced pluripotent stem cells (iPSC). Lack of functional TBCK protein in iNPC is associated with impaired endoplasmic reticulum-to-Golgi vesicle transport and autophagosome biogenesis, as well as altered cell cycle progression and severe impairment in the capacity of migration. Alteration in these processes, which are crucial for neurogenesis, neuronal migration, and cytoarchitecture organization, may represent an important causative mechanism of both neurodevelopmental and neurodegenerative phenotypes observed in IHPRF3. Whether reduced mechanistic target of rapamycin (mTOR) signaling is secondary to impaired TBCK function over other secretory transport regulators still needs further investigation.

Abstract Purpose The term “pectoralis minor syndrome” refers to this constellation of symptoms that can occur when the pectoralis minor (Pm) is shortened and contracted. Release of the tendon of the Pm from the coracoid has been reported to provide substantial clinical improvement to patients presenting with pectoralis minor syndrome. The purpose of this study was (1) to describe the technique for endoscopic release of pectoralis minor tendon at the subdeltoid space, (2) to classify the pectoralis minor syndrome according to its severity and (3) and to report the short‐term outcomes of this procedure in a consecutive series of patients diagnosed with pectoralis minor syndrome. Methods Endoscopic release of the pectoralis minor tendon was performed in a series of 10 patients presenting with pectoralis minor syndrome. There were six females and four males with a median age at the time of surgery of 42 (range from 20 to 58) years. Four shoulders were categorized as grade I (scapular dyskinesis), and six as grade II (intermittent brachial plexopathy). Shoulders were evaluated for pain, motion, satisfaction, subjective shoulder value (SSV), quick‐DASH, ASES score, and complications. The mean follow‐up time was 19 (range, 6 to 49) months. Results Arthroscopic release of the tendon of the Pm led to substantial resolution of pectoralis minor syndrome symptoms in all but one shoulder, which was considered a failure. Preoperatively, the median VAS for pain was 8.5 (range, 7–10) and the mean SSV was 20% (range, 10% ‐ 50%). At most recent follow‐up the mean VAS for pain was 1 (range, 0–6) and the mean SSV 80% (range, 50% ‐ 90%). Before surgery, mean ASES and quick‐DASH scores were 19.1 (range, 10–41.6) and 83.1 (range, 71 and 95.5) points respectively. At most recent follow‐up, mean ASES and quick‐DASH scores were 80.1 (range, 40–100) and 19.3 (range, 2.3–68) points respectively. No surgical complications occurred in any of the shoulder included in this study. Conclusions Endoscopic release of the tendon of the pectoralis minor from the coracoid improves pain, function and patient reported outcomes in the majority of patients presenting with the diagnosis of isolated pectoralis minor syndrome.

Biallelic pathogenic variants in TBCK cause encephaloneuropathy, infantile hypotonia with psychomotor retardation, and characteristic facies 3 (IHPRF3). The molecular mechanisms underlying its neuronal phenotype are largely unexplored. In this study, we reported two sisters, who harbored biallelic variants in TBCK and met diagnostic criteria for IHPRF3. We provided evidence that TBCK may play an important role in the early secretory pathway in neuroprogenitor cells (iNPC) differentiated from induced pluripotent stem cells (iPSC). Lack of functional TBCK protein in iNPC is associated with impaired endoplasmic reticulum-to-Golgi vesicle transport and autophagosome biogenesis, as well as altered cell cycle progression and severe impairment in the capacity of migration. Alteration in these processes, which are crucial for neurogenesis, neuronal migration, and cytoarchitecture organization, may represent an important causative mechanism of both neurodevelopmental and neurodegenerative phenotypes observed in IHPRF3. Whether reduced mechanistic target of rapamycin (mTOR) signaling is secondary to impaired TBCK function over other secretory transport regulators still needs further investigation. [ABSTRACT FROM AUTHOR]

Background: Signal transducing adaptor molecule 1 (STAM1) was considered to mediate cell growth and be involved in multiple signaling pathways; however, no research on the role of STAM1 in any tumors has been published yet. Our study aimed to investigate the prognostic value of STAM1 for clear cell renal cell carcinoma (ccRCC) and its role in modulating cancer cell function.Methods: Data from The Cancer Genome Atlas (TCGA) in December 2019 were used to examine the role of STAM1 in indicating ccRCC patients' survival. A purchased tissue microarray (TM) and fresh ccRCC renal tissues were used for further validation. Then, STAM1 was overexpressed in human ccRCC cell lines for in vitro assays. Finally, bioinformatics was performed for STAM1 protein–protein interaction (PPI) network construction and functional analyses.Results: A total of 539 ccRCC and 72 control samples were included for the TCGA cohort, and 149 ccRCC and 29 control slices were included for the TM cohort. In the TCGA and TM cohorts, we found that STAM1 expression was lower in ccRCC compared with normal adjacent non-cancerous renal tissues (P < 0.0001 for both cohorts). STAM1 downregulation was also related to significantly shorter overall survival (OS) (P < 0.0001 for both cohorts). In the TCGA cohort, reduced STAM1 expression was also associated with aggressive features of the tumor. Under multivariate analyses, STAM1 was demonstrated to be an independent prognostic factor for ccRCC survival in both TCGA (HR = 0.52, 95% CI: 0.33–0.84, P = 0.007) and TM cohorts (HR = 0.12, 95% CI: 0.04–0.32, P < 0.001). Our in vitro experiments showed that STAM1 inhibited cell viability, invasion, and migration in ccRCC cell lines. In PPI network, 10 candidate genes categorized into five biological processes were found to be closely related to STAM1.Conclusion: STAM1 is a promising prognostic biomarker for predicting ccRCC survival outcomes. Preliminary pathogenesis is demonstrated by our in vitro experiments. Further pathological mechanisms of STAM1 in modulating ccRCC require comprehensive laboratory and clinical studies.

Background: Signal transducing adaptor molecule 1 (STAM1) was considered to mediate cell growth and be involved in multiple signaling pathways; however, no research on the role of STAM1 in any tumors has been published yet. Our study aimed to investigate the prognostic value of STAM1 for clear cell renal cell carcinoma (ccRCC) and its role in modulating cancer cell function. Methods: Data from The Cancer Genome Atlas (TCGA) in December 2019 were used to examine the role of STAM1 in indicating ccRCC patients' survival. A purchased tissue microarray (TM) and fresh ccRCC renal tissues were used for further validation. Then, STAM1 was overexpressed in human ccRCC cell lines for in vitro assays. Finally, bioinformatics was performed for STAM1 protein–protein interaction (PPI) network construction and functional analyses. Results: A total of 539 ccRCC and 72 control samples were included for the TCGA cohort, and 149 ccRCC and 29 control slices were included for the TM cohort. In the TCGA and TM cohorts, we found that STAM1 expression was lower in ccRCC compared with normal adjacent non-cancerous renal tissues (P < 0.0001 for both cohorts). STAM1 downregulation was also related to significantly shorter overall survival (OS) (P < 0.0001 for both cohorts). In the TCGA cohort, reduced STAM1 expression was also associated with aggressive features of the tumor. Under multivariate analyses, STAM1 was demonstrated to be an independent prognostic factor for ccRCC survival in both TCGA (HR = 0.52, 95% CI: 0.33–0.84, P = 0.007) and TM cohorts (HR = 0.12, 95% CI: 0.04–0.32, P < 0.001). Our in vitro experiments showed that STAM1 inhibited cell viability, invasion, and migration in ccRCC cell lines. In PPI network, 10 candidate genes categorized into five biological processes were found to be closely related to STAM1. Conclusion: STAM1 is a promising prognostic biomarker for predicting ccRCC survival outcomes. Preliminary pathogenesis is demonstrated by our in vitro experiments. Further pathological mechanisms of STAM1 in modulating ccRCC require comprehensive laboratory and clinical studies. [ABSTRACT FROM AUTHOR]

Introduction: In 2017, the European Academy of Otology and Neurotology and the Japanese Otological Society published Joint Consensus Statements on the Definitions, Classification and Staging of Middle Ear Cholesteatoma. The aim of this work is an application of the new classification system at the Department of Otorhinolaryngology and Head and Neck Surgery of the University Hospital Hradec Králové. Material and Methods: Authors retrospectively revised a group of patients who underwent surgery for chronic otitis media with cholesteatoma in years 2013–2017. A total of 104 patients, 56 males and 48 females, were enrolled in the study. Results: A total of 142 surgeries (77 primary, 65 secondary) revealed 116 cholesteatomas of which 3 remained unclassifiable. A congenital cholesteatoma was found in 4 patients, an acquired cholesteatoma was found in 70 cases (60.3%). The most common type was retraction pocket cholesteatoma (60 surgeries, 51.7%), with predominance of pars flaccida cholesteatomas. Acquired non-retraction pocket cholesteatomas were less common (10 surgeries, 8.6%), where secondary to tympanic membrane cholesteatomas predominated (6 surgeries, 5.2%). Of the 65 secondary surgeries, 39 cholesteatomas were found (33.6%), residual cholesteatomas were found in 20 patients (17.2%), and recurrent cholesteatomas were found in 19 patients (16.4%). Stage I cholesteatoma was found in 42 (36.2%) patients, stage II cholesteatoma in 60 (51.7%) patients, stage III cholesteatoma in 13 (11.2%) patients and stage IV cholesteatoma in a single patient (1.0%). Authors further examine incidence of cholesteatoma types in comparison with STAM sites. Conclusion: New cholesteatoma classification systems have potential to build unified database of patients with chronic suppurative otitis media with cholesteatoma. It will be certainly a benefit to continue to prospectively expand the database. [ABSTRACT FROM AUTHOR]

The social, psychological, physical, and financial benefits of digital inclusion are of increasing importance for older persons. However, older persons are often less inclined to utilise technological communication with reports of perceived poor technology acceptance. In this context, a study was conducted to investigate communication technology acceptance in older persons living in residential care. A cross sectional survey of residents (≥60 yrs) of four inner city residences in Durban, South Africa was conducted to assess communication technology access and technology acceptance defined as Usage Behaviour. A researcher-administered questionnaire was based on the Senior Technology Acceptance Model (STAM). Descriptive statistics of STAM factors and structural equation model (SEM) were conducted to test this model, to quantify the importance of various technology acceptance factors on Usage Behaviour among older persons living in residential care. The survey had a 72.1% response rate (n=277). Most of the respondents owned mobile phones (87.6%), although there was low smartphone ownership. Family desire to communicate and ease of use motivated mobile phone acquisition. Behaviour Intention, Facilitating Conditions, Attitude to Life and Satisfaction and education level were significantly associated with Usage Behaviour. Gerontechnology Anxiety and Age showed significant negative associations with Usage Behaviour. The acceptance of communication technology in this setting was low and predominantly influenced by Attitudinal and Technological Context factors together with age and education. [ABSTRACT FROM AUTHOR]

The aim of this study is to analyze the questions of the Arabic language examinations of Sijil Tinggi Agama Malaysia (STAM) for three years from 2013 to 2015 in the light of Bloom's Taxonomy levels. In this study, the researchers relied on the analytical descriptive approach. The number of exam questions for grammar and morphology in Malaysia's STAM certificate was 222. The study found that the questions on the level of understanding came first in the exam questions for grammar and morphology, with 93 questions or 42% of the total. While the level of remembering came in second place with 62 recurrences or 28%, followed by the questions on the level of analysis, with a frequency of 34 questions or 16%. The level of application came last, with 33 recurrences or 14% of the total. The two levels of evaluation and creativity were not showing any frequency. [ABSTRACT FROM AUTHOR]

Revealing the role of non-coding RNAs (ncRNAs) in inducing dysregulated pathological responses to external signals may identify therapeutic targets for inhibiting the progression of clear cell renal cell carcinoma (ccRCC). Non-coding RNAs belong to a class of RNA molecules that do not encode proteins but possess diverse biological functions, playing essential roles in the occurrence and development of metastatic and proliferative tumors. To investigate the impact of the upstream interaction between miR-142-3p and lncRNA MAGI2-AS3 on the tumor-suppressive activity of the STAM gene, we firstly conducted bioinformatics analysis to predict the upstream miRNAs of STAM and the upstream lncRNAs of the miRNAs through online databases (miRanda, miRDB, TargetScan, LncBase v2), which were further validated by the starBasev2.0 database. Subsequently, multiple experimental techniques were employed to validate these findings, including RT-qPCR, Western blotting, measurement of cellular functional activity, and luciferase reporter assays. Through these experimental methods, we provided compelling evidence regarding the role of miR-142-3p and MAGI2-AS3 in regulating STAM gene expression and functionality, revealing their potential significance in tumor suppression. Our research demonstrates the importance of the MAGI2-AS3/miR-142-3p/STAM signaling pathway axis in ccRCC. MAGI2-AS3 competes for binding with miR-142-3p, resulting in upregulated STAM gene expression. This upregulation inhibits tumor proliferation and metastasis in ccRCC cells. Conversely, overexpression of miR-142-3p or silencing of MAGI2-AS3 promotes tumor behavior, while downregulation of miR-142-3p inhibits the development of ccRCC. Targeting the MAGI2-AS3/miR-142-3p/STAM axis holds promise as a therapeutic strategy for ccRCC treatment. • MAGI2-AS3 impacts ccRCC cell proliferation, migration, and apoptosis. • MAGI2-AS3 sponges miR-142-3p, weakening its inhibitory effect on STAM. • The MAGI2-AS3/miR-142-3p/STAM axis influences ccRCC cell progression. • A prognostic model of genetically related ccRCC was constructed. [ABSTRACT FROM AUTHOR]

Kallah Rabbati is a little-known late amoraic (c. 350–400 CE) rabbinic text with a close relationship to the Babylonian Talmud. Passages in Kallah Rabbati parallel passages in the Talmud with variations that expose the redactional process of both texts. How the Talmud was redacted is one of the enigmas of Talmudic studies. To date, that analysis has been tautological: deciphering how the Talmud was edited from data gathered exclusively from the Talmud itself. This study shows that Kallah Rabbati can be an invaluable aid in uncovering that process, pointing to the transmitters as having played a crucial role in the editing of some Talmudic passages and even at times comprising its anonymous voice.

Nascent cargo proteins in the endoplasmic reticulum are transported to the Golgi by COPII carriers. Typical COPII vesicles are 60–70 nm in diameter, and much larger macromolecules, such as procollagen, are transported by atypical large COPII carriers in mammalian cells. The formation of large COPII carriers is enhanced by Cul3 ubiquitin ligase, which mono-ubiquitinates Sec31A, a COPII coat protein. However, the deubiquitinating enzyme for Sec31A was unclear. Here, we show that the deubiquitinating enzyme USP8 interacts with and deubiquitinates Sec31A. The interaction was mediated by the adaptor protein STAM1. USP8 overexpression inhibited the formation of large COPII carriers. By contrast, USP8 knockdown caused the accumulation of COPII coat proteins around the cis -Golgi, promoted the intracellular trafficking of procollagen IV from the endoplasmic reticulum to the Golgi, and increased collagen IV secretion. We concluded that USP8 deubiquitinates Sec31A and inhibits the formation of large COPII carriers, thereby suppressing collagen IV secretion. [ABSTRACT FROM AUTHOR]

Hepatic fibrosis can result as a pathological response to nonalcoholic steatohepatitis (NASH). Cirrhosis, the late stage of fibrosis, has been linked to poor survival and an increased risk of developing hepatocellular carcinoma, with limited treatment options available. Therefore, there is an unmet need for novel effective antifibrotic compounds. Cyclophilins are peptidyl-prolyl cis-trans isomerases that facilitate protein folding and conformational changes affecting the function of the targeted proteins. Due to their activity, cyclophilins have been presented as key factors in several stages of the fibrotic process. In this study, we investigated the antifibrotic effects of NV556, a novel potent sanglifehrin-based cyclophilin inhibitor, in vitro and in vivo. NV556 potential antifibrotic effect was evaluated in two well-established animal models of NASH, STAM, and methionine-choline-deficient (MCD) mice, as well as in an in vitro 3D human liver ECM culture of LX2 cells, a human hepatic stellate cell line. We demonstrate that NV556 decreased liver fibrosis in both STAM and MCD in vivo models and decreased collagen production in TGFβ1-activated hepatic stellate cells in vitro. Taken together, these results present NV556 as a potential candidate for the treatment of liver fibrosis.

In this paper, we studied, at first, the influence of the energy-dependent potentials on the one-dimensionless Klein-Gordon oscillator. Then, the Shannon entropy and Fisher information of this system are investigated. The position and momentum information entropies for the low-lying states n = 0, 1, 2 are calculated. Some interesting features of both Fisher and Shannon densities, as well as the probability densities, are demonstrated. Finally, the Stam, Cramer-Rao and Bialynicki-Birula-Mycielski (BBM) inequalities have been checked, and their comparison with the regarding results have been reported. We showed that the BBM inequality is still valid in the form Sx+Sp ≥ 1+lnπ, as well as in ordinary quantum mechanics. [ABSTRACT FROM AUTHOR]

The objective of this article is to outline a hitherto neglected aspect of writing holy scrolls for ritual use, which in medieval Europe became a crucial subject of discussion: the ritual consecration of certain processes during the manufacturing of STaM with a special emphasis on writable skins. Taking into account Jewish and Christian sources, many of which have not been scrutinized to date, a paradox that perfectly reflects the ambivalent relationship of Jews and Christians in the Middle Ages will be revealed. On the one hand, the ritual sanctification can be read as an act of demarcation by which Jews drew a clear line between holy and profane--and Jews and non-Jews. On the other hand, it becomes evident that there was not only an artisanal exchange but a mutual interaction in terms of ritual and performance as well. [ABSTRACT FROM AUTHOR]

The article focuses on the use of adapted subversion in the 1975 film "The Rocky Horror Picture Show." Topics covered include the framing of the film within Robert Stam's adaptation theory, the common traits of Gothic novels such as tyrannical foreigners, swooning heroines, and labyrinthine castles, and the film's use of taboo sex and rock 'n' roll as tools of subversion.

The Rb tumor suppressor is conserved in Drosophila, and its inactivation can lead to cell proliferation or death depending on the specific cellular context. Therefore, identifying genes that affect the survival of Rb-mutant cells can potentially identify novel targets for therapeutic intervention in cancer. From a genetic screen in Drosophila, we identified synthetic lethal interactions between mutations of fly Rb (rbf) and the ESCRT-0 components stam and hrs. We show that inactivation of ESCRT-0 sensitizes rbf-mutant cells to undergo apoptosis through inhibition of EGFR signaling and accumulation of Hid protein. Mutation of stam inhibits EGFR signaling upstream of secreted Spi and downstream of Rhomboid expression, and causes Rhomboid protein to accumulate in the abnormal endosomes labeled with both the early and late endosomal markers Rab5 and Rab7. These results reveal that ESCRT-0 mutants inhibit EGFR signaling by disrupting Rhomboid endosomal trafficking in the ligand-producing cells. Because ESCRT-0 also plays crucial roles in EGFR downregulation after ligand binding, this study provides new insights into how loss of ESCRT-0 function can either increase or decrease EGFR signaling. [ABSTRACT FROM AUTHOR]

Keywords: stam; clear cell renal carcinoma; prognosis; cell growth & apoptosis; invasion EN stam clear cell renal carcinoma prognosis cell growth & apoptosis invasion 1 2 2 09/13/21 20210908 NES 210908 In the original article, there was a mistake in the histogram of Figure 7B as published. Stam, clear cell renal carcinoma, prognosis, cell growth & apoptosis, invasion. [Extracted from the article]

The number of surface membrane proteins and their residence time on the plasma membrane are critical determinants of cellular responses to cues that can control plasticity, growth and differentiation. After internalization, the ultimate fate of many plasma membrane proteins is dependent on whether they are sorted for internalization into the lumenal vesicles of multivesicular bodies (MVBs), an obligate step prior to lysosomal degradation. To help to elucidate the mechanisms underlying MVB sorting, we have developed a novel cell-free assay that reconstitutes the sorting of a prototypical membrane protein, the epidermal growth factor receptor, with which we have probed some of its molecular requirements. The sorting event measured is dependent on cytosol, ATP, time, temperature and an intact proton gradient. Depletion of Hrs inhibited biochemical and morphological measures of sorting that were rescued by inclusion of recombinant Hrs in the assay. Moreover, depletion of signal-transducing adaptor molecule (STAM), or addition of mutated ATPase-deficient Vps4, also inhibited sorting. This assay reconstitutes the maturation of late endosomes, including the formation of internal vesicles and the sorting of a membrane protein, and allows biochemical investigation of this process. [ABSTRACT FROM AUTHOR]

Abstract: STAM (signal-transducing adaptor molecule) is a protein highly conserved from yeast to mammals. In Drosophila melanogaster the basic molecular architecture of the protein is comprised of a N-terminal VHS domain, an ubiquitin-interacting motif and a central Src homology-3 domain. In this paper we examine the expression pattern of the stam gene and the localisation of the STAM protein during D. melanogaster oogenesis. Its transcript is present throughout egg chamber development in all germ-line cells, including the oocyte. dSTAM is firstly detected in germarial region 2, where the protein is present in the newly formed germ-line cysts and is mainly accumulated into the oocyte. As oogenesis proceeds, dSTAM is enriched in the perinuclear region of the nurse cells and is also found in the somatic polar follicular cells. In the oocyte, the protein is more abundant posteriorly and becomes restricted to the posterior pole just before disappearing at stage 10b. We show that dSTAM localisation is unaffected in the oocyte of grk mutant egg chambers, indicating that it is not dependent on the polarity of the microtubule network. In contrast, dSTAM distribution is remarkably altered in cup mutant oocytes where the protein accumulates in a round central spot and never reaches the posterior pole. [Copyright &y& Elsevier]

Abstract: Signal transducing adaptor molecule (STAM) complexed with hepatocyte growth factor regulated tyrosine kinase substrate (Hrs) works on sorting of cargo proteins in multivesicular body (MVB) pathway. Associated molecule with SH3 domain of STAM (AMSH), a zinc-containing ubiquitin isopeptidase, is thought to play a role in regulation of ubiquitin-mediated degradation by binding to STAM. We have found that AMSH requires the conformation of Px(V/I)(D/N)RxxKP sequence to bind SH3 domain of STAM with ∼7μM affinity, and that the isolated C-terminal domain of AMSH contains the isopeptidase activity. Deubiquitination by AMSH was assisted when ubiquitins were bound to STAM which can bind to AMSH simultaneously. With the specificity toward K63-linked ubiquitins, this facilitated ubiquitin processing activity of AMSH may imply a distinct regulatory mechanism for sorting and degradation through STAM binding. [Copyright &y& Elsevier]

[Display omitted] Hepatocellular carcinoma (HCC), the most common primary liver cancer, arises after a long period of exposure to etiological factors. Nonalcoholic steatohepatitis (NASH) is ranked as the main risk factor for developing HCC; hence, experimental models of NASH leading to HCC have become key tools both to investigate the molecular mechanisms underlying the pathophysiology and to evaluate new putative drugs for treating chronic liver diseases in humans. Animal models of NASH induced by a high-fat diet (HFD) plus chemical inducers, such as the NASH-HCC (STAM), high-fat diet/diethylnitrosamine (HFD/DEN), choline-deficient high-fat diet/DEN (CDHFD/DEN), and Western diet/carbon tetrachloride (WD/CCl 4) models, are promising because they exacerbate liver damage and significantly shorten the experimental time. In this review, we critically summarize and discuss the ability of these models to recapitulate the liver alterations that precede and lead to HCC progression, as well as the impact of the diet in promoting liver injury progression. We also emphasize the strengths and weaknesses of the models' ability to closely mimic the stages of liver injury development that occur in humans. Based on the molecular mechanisms induced by the currently available NASH models leading to HCC, we argue that although several NASH models have importantly contributed to describing the disease chronology, the progress in emulating the progression from NASH to HCC has been partial. Thus, the development of novel NASH/HCC models remains an unmet need. [ABSTRACT FROM AUTHOR]

Hepatic fibrosis can result as a pathological response to nonalcoholic steatohepatitis (NASH). Cirrhosis, the late stage of fibrosis, has been linked to poor survival and an increased risk of developing hepatocellular carcinoma, with limited treatment options available. Therefore, there is an unmet need for novel effective antifibrotic compounds. Cyclophilins are peptidyl-prolyl cis-trans isomerases that facilitate protein folding and conformational changes affecting the function of the targeted proteins. Due to their activity, cyclophilins have been presented as key factors in several stages of the fibrotic process. In this study, we investigated the antifibrotic effects of NV556, a novel potent sanglifehrin-based cyclophilin inhibitor, in vitro and in vivo. NV556 potential antifibrotic effect was evaluated in two well-established animal models of NASH, STAM, and methionine-choline-deficient (MCD) mice, as well as in an in vitro 3D human liver ECM culture of LX2 cells, a human hepatic stellate cell line. We demonstrate that NV556 decreased liver fibrosis in both STAM and MCD in vivo models and decreased collagen production in TGFβ1-activated hepatic stellate cells in vitro. Taken together, these results present NV556 as a potential candidate for the treatment of liver fibrosis. [ABSTRACT FROM AUTHOR]