bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complex regulation of mitochondrial signaling by human adenovirus minor capsid protein VI
Authors: Schubert Erik , Mun Kwangchol , Larsson Mårten , Panagiotou Styliani , Idevall-Hagren Olof , Svensson Catharina , Punga Tanel 
Published: June 2024

ABSTRACT

The controlled release of mitochondrial content into the cytosol has emerged as one of the key steps in mitochondrial signaling. In particular, the release of mitochondrial DNA (mtDNA) into the cytosol has been shown to activate interferon beta (IFN-β) gene expression to execute the innate immune response. In this report, we show that human adenovirus type 5 (HAdV-C5) infection induces the release of mtDNA into the cytosol. The release of mtDNA is mediated by the viral minor capsid protein VI (pVI), which localizes to mitochondria. The presence of the mitochondrial membrane proteins Bak and Bax are needed for the mtDNA release, whereas the viral E1B-19K protein blocked pVI-mediated mtDNA release. Surprisingly, the pVI-mediated mtDNA release did not increase but inhibited the IFN-β gene expression. Notably, the pVI expression caused mitochondrial leakage of the HSP60 protein. The latter prevented specific phosphorylation of the interferon regulatory factor 3 (IRF3) needed for IFN-β gene expression. Overall, we assign a new mitochondria and IFN-β signaling-modulating function to the HAdV-C5 minor capsid protein VI.

IMPORTANCE
Human adenoviruses (HAdVs) are common pathogens causing various self-limiting diseases, including conjunctivitis and the common cold. HAdVs need to interfere with multiple cellular signaling pathways during the infection to gain control over the host cell. In this study, we identified human adenovirus type 5 (HAdV-C5) minor capsid protein VI as a factor modulating mitochondrial membrane integrity and mitochondrial signaling. We show that pVI-altered mitochondrial signaling impedes the cell’s innate immune response, which may benefit HAdV growth. Overall, our study provides new detailed insights into the HAdV-mitochondria interactions and signaling. This knowledge is helpful when developing new anti-viral treatments against pathogenic HAdV infections and improving HAdV-based therapeutics.
Generation of single-round infectious rotavirus with a mutation in the intermediate capsid protein VP6
Authors: Kotaki Tomohiro , Kanai Yuta , Onishi Megumi , Minami Shohei , Chen Zelin , Nouda Ryotaro , Nurdin Jeffery A. , Yamasaki Moeko , Kobayashi Takeshi 
Published: June 2024

ABSTRACT

Rotavirus causes severe diarrhea in infants. Although live attenuated rotavirus vaccines are available, vaccine-derived infections have been reported, which warrants development of next-generation rotavirus vaccines. A single-round infectious virus is a promising vaccine platform; however, this platform has not been studied extensively in the context of rotavirus. Here, we aimed to develop a single-round infectious rotavirus by impairing the function of the viral intermediate capsid protein VP6. Recombinant rotaviruses harboring mutations in VP6 were rescued using a reverse genetics system. Mutations were targeted at VP6 residues involved in virion assembly. Although the VP6-mutated rotavirus expressed viral proteins, it did not produce progeny virions in wild-type cells; however, the virus did produce progeny virions in VP6-expressing cells. This indicates that the VP6-mutated rotavirus is a single-round infectious rotavirus. Insertion of a foreign gene, and replacement of the VP7 gene segment with that of human rotavirus clinical isolates, was successful. No infectious virions were detected in mice infected with the single-round infectious rotavirus. Immunizing mice with the single-round infectious rotavirus induced neutralizing antibody titers as high as those induced by wild-type rotavirus. Taken together, the data suggest that this single-round infectious rotavirus has potential as a safe and effective rotavirus vaccine. This system is also applicable for generation of safe and orally administrable viral vectors.

IMPORTANCE
Rotavirus, a leading cause of acute gastroenteritis in infants, causes an annual estimated 128,500 infant deaths worldwide. Although live attenuated rotavirus vaccines are available, they are replicable and may cause vaccine-derived infections. Thus, development of safe and effective rotavirus vaccine is important. In this study, we report the development of a single-round infectious rotavirus that can replicate only in cells expressing viral VP6 protein. We demonstrated that (1) the single-round infectious rotavirus did not replicate in wild-type cells or in mice; (2) insertion of foreign genes and replacement of the outer capsid gene were possible; and (3) it was as immunogenic as the wild-type virus. Thus, the mutated virus shows promise as a next-generation rotavirus vaccine. The system is also applicable to orally administrable viral vectors, facilitating development of vaccines against other enteric pathogens.
Inflammatory caspase substrate specificities
Authors: Exconde Patrick M. , Bourne Christopher M. , Kulkarni Madhura , Discher Bohdana M. , Taabazuing Cornelius Y. 
Published: June 2024

ABSTRACT

Caspases are a family of cysteine proteases that act as molecular scissors to cleave substrates and regulate biological processes such as programmed cell death and inflammation. Extensive efforts have been made to identify caspase substrates and to determine factors that dictate substrate specificity. Thousands of putative substrates have been identified for caspases that regulate an immunologically silent type of cell death known as apoptosis, but less is known about substrates of the inflammatory caspases that regulate an immunostimulatory type of cell death called pyroptosis. Furthermore, much of our understanding of caspase substrate specificities is derived from work done with peptide substrates, which do not often translate to native protein substrates. Our knowledge of inflammatory caspase biology and substrates has recently expanded and here, we discuss the recent advances in our understanding of caspase substrate specificities, with a focus on inflammatory caspases. We highlight new substrates that have been discovered and discuss the factors that engender specificity. Recent evidence suggests that inflammatory caspases likely utilize two binding interfaces to recognize and process substrates, the active site and a conserved exosite.
Heat Shock Proteins on Tumor Cell Surface as Target for Anti-Tumor Therapy (A Review)
Authors: Makarova A. O. , Kostenko V. V. , Ovsyanikova O. V. , Svirshchevskaya E. V. , Lutsenko G. V. , Sapozhnikov A. M. 
Published: June 2024

Abstract
According to WHO, cancer is the cause of ~5 million deaths annually. To date, there is no universal solution to fight cancer despite outstanding achievements of radiotherapy, chemotherapy, and immunotherapy. In this regard, there is a need to develop new approaches to antitumor therapy, in particular based on the search and use of targeted molecules that allow killing tumor cells of various types with high efficiency without significant toxic effects on healthy organs and tissues. This review presents the characteristics of the main proteins of the heat shock proteins (HSP) family, the features of their expression in tumor cells, and the possibility of using monoclonal antibodies against these proteins as a guiding vector for antitumor immunotherapy.
Assessing the causal role of physical activity and leisure sedentary behaviours with chronic obstructive pulmonary disease: a Mendelian randomisation study
Authors: Xiao Lu , Li Weina , Li Fawei , Chen Xingjuan , Xu Yun , Hu Ying , Fu Yingkun , Feng Ling 
Published: June 2024

BackgroundObservational studies show that patients with chronic obstructive pulmonary disease (COPD) tend to be sedentary during leisure time. Physical activity (PA) may reduce the risk of COPD, but the causal relationship is unclear. We used a Mendelian randomisation (MR) method to elucidate the association of leisure sedentary behaviours (LSB) and PA with lung function and COPD.MethodsData on LSB (n=422 218), PA (n=608 595), COPD (n=299 929) and lung function (n=79 055) were obtained from the large-scale genome-wide association study. Causal inference used inverse variance-weighted, MR-Egger and weighted median. Sensitivity analysis was performed to assess heterogeneity and pleiotropy, and radial MR was used to distinguish outliers. The primary outcome was analysed by multifactorial MR adjusted for daily smoking.ResultsThe inverse variance weighted analysis indicated that increased moderate-to-vigorous PA (MVPA) is associated with higher levels of forced vital capacity (FVC) (beta=0.27, 95% CI 0.12 to 0.42; p=3.51×10–4). For each increment of 2.8 hours in television watching, the odds of COPD were 2.25 times greater (OR=2.25; 95% CI 1.84 to 2.75; p=2.38×10–15). For early-onset COPD, the odds were 2.11 times greater (OR=2.11; 95% CI 1.56 to 2.85; p=1.06×10–6), and for late-onset COPD, the odds were 2.16 times greater (OR=2.16; 95% CI 1.64 to 2.84; p=3.12×10–8). Similarly, the odds of hospitalisation for COPD were 2.02 times greater with increased television watching (OR=2.02; 95% CI 1.59 to 2.55; p=4.68×10–9). Television watching was associated with lower FVC (beta=−0.19, 95% CI −0.28 to −0.10; p=1.54×10–5) and forced expiratory volume in the 1 s (FEV1) (beta=−0.16, 95% CI −0.25 to −0.08; p=1.21×10–4) levels. The results remained significant after adjustment for smoking.ConclusionsOur study suggests a potential association with LSB, particularly television watching, is associated with higher odds of COPD and lower indices of lung function as measured continuously, including FEV1 and FVC. Conversely, an increase in MVPA is associated with higher indices of lung function, particularly reflected in increased FVC levels.
Laparoscopic lateral suspension (Dubuisson) in the treatment of pelvic organ prolapse
Authors: Luo Can , Wei Dongmei , Chen Yueyue , Mei Ling , Niu Xiaoyu 
Published: June 2024

BackgroundCurrently, the global ageing population is becoming increasingly severe, and the incidence of pelvic organ prolapse (POP) is rising year by year, which seriously impacts the psychosomatic health and the quality of life in female patients. Surgical treatments for POP still face enormous challenges.MethodsThe aim of this review is to discuss the laparoscopic lateral suspension (LLS) approach to the management of POP. We use MeSH terms for each topic to retrieve relevant literature from the PubMed and Embase databases. Our group reviewed, synthesised and summarised included studies.ResultsLLS has been widely applied in the treatment of middle pelvic compartment defects. In comparison to sacrocolpopexy (SC), the most significant advantage of LLS is that it avoids dissecting the complex sacral region and possesses simple surgical procedures. But its cure, recurrence, reoperation and complication rates have been widely discussed. Issues regarding its value and its potential equivalence in surgical therapeutic effects compared with SC have gained continuous attention.ConclusionsBased on the existing research, LLS demonstrates advantages in the treatment of POP, particularly in cases of middle pelvic compartment defects. However, solely based on current clinical studies, it is premature to establish superiority or inferiority compared with SC. LLS is not yet a substitute for SC.
Relationship between the change of ATP level controlled by ectonucleotidases and endometriosis-associated infertility and pain
Authors: Wang Yiling , Zhai Qingjie , Tian Zhao , Chang Xiaohong , Zhu Honglan 
Published: June 2024

BackgroundThe dysfunction of the immune system is one of the pathogeneses of endometriosis. Immune cells can not only affect the microenvironment of the endometrium by secreting cytokines and defensins but also promote angiogenesis, growth and invasion of endometrial stromal cells.ResultATP is a key mediator in the immune mechanism of endometriosis and plays a crucial role in endometriosis. While ATP acts as a purinergic signalling molecule, it has a close relationship with the pain of endometriosis via activating ATP receptors, including P2X3, P2X4, P2X7 and P2Y receptors, after being activated by the immune system. Besides, ATP levels reflect the impairment of mitochondrial function in granulosa cells, which could lead to infertility. The modulation of ATP expression levels is controlled by ectonucleotidases. The content of ectonucleotidases is altered in endometriosis which may be emerging non-invasive biomarkers.ConclusionIn the present review, we briefly introduce the relationship between the change of ATP level controlled by ectonucleotidases and endometriosis-associated infertility and pain, and illustrate our prospects for future research.
Protective function of sclerosing cholangitis on IBD
Authors: Bedke Tanja , Stumme Friederike , Tomczak Miriam , Steglich Babett , Jia Rongrong , Bohmann Simon , Wittek Agnes , Kempski Jan , Göke Emilia , Böttcher Marius , Reher Dominik , Franke Anissa , Lennartz Maximilian , Clauditz Till , Sauter Guido , Fründt Thorben , Weidemann Sören , Tiegs Gisa , Schramm Christoph , Gagliani Nicola , Pelczar Penelope , Huber Samuel 
Published: June 2024

Objective
There is a strong clinical association between IBD and primary sclerosing cholangitis (PSC), a chronic disease of the liver characterised by biliary inflammation that leads to strictures and fibrosis. Approximately 60%–80% of people with PSC will also develop IBD (PSC-IBD). One hypothesis explaining this association would be that PSC drives IBD. Therefore, our aim was to test this hypothesis and to decipher the underlying mechanism.

Design

Colitis severity was analysed in experimental mouse models of colitis and sclerosing cholangitis, and people with IBD and PSC-IBD. Foxp3
+
Treg-cell infiltration was assessed by qPCR and flow cytometry. Microbiota profiling was carried out from faecal samples of people with IBD, PSC-IBD and mouse models recapitulating these diseases. Faecal microbiota samples collected from people with IBD and PSC-IBD were transplanted into germ-free mice followed by colitis induction.

Results

We show that sclerosing cholangitis attenuated IBD in mouse models. Mechanistically, sclerosing cholangitis causes an altered intestinal microbiota composition, which promotes Foxp3
+
Treg-cell expansion, and thereby protects against IBD. Accordingly, sclerosing cholangitis promotes IBD in the absence of Foxp3
+
Treg cells. Furthermore, people with PSC-IBD have an increased Foxp3
+
expression in the colon and an overall milder IBD severity. Finally, by transplanting faecal microbiota into gnotobiotic mice, we showed that the intestinal microbiota of people with PSC protects against colitis.

Conclusion
This study shows that PSC attenuates IBD and provides a comprehensive insight into the mechanisms involved in this effect.
Effectiveness of mailed outreach and patient navigation to promote HCC screening process completion: a multicentre pragmatic randomised clinical trial
Authors: Singal Amit G , Narasimman Manasa , Daher Darine , Yekkaluri Sruthi , Liu Yan , Lee MinJae , Cerda Vanessa , Khan Aisha , Seif El Dahan Karim , Kramer Jennifer , Gopal Purva , Murphy Caitlin , Hernaez Ruben 
Published: June 2024

BackgroundHepatocellular carcinoma (HCC) is plagued by failures across the cancer care continuum, leading to frequent late-stage diagnoses and high mortality. We evaluated the effectiveness of mailed outreach invitations plus patient navigation to promote HCC screening process completion in patients with cirrhosis.MethodsBetween April 2018 and September 2021, we conducted a multicentre pragmatic randomised clinical trial comparing mailed outreach plus patient navigation for HCC screening (n=1436) versus usual care with visit-based screening (n=1436) among patients with cirrhosis at three US health systems. Our primary outcome was screening process completion over a 36-month period, and our secondary outcome was the proportion of time covered (PTC) by screening. All patients were included in intention-to-screen analyses.ResultsAll 2872 participants (median age 61.3 years; 32.3% women) were included in intention-to-screen analyses. Screening process completion was observed in 6.6% (95% CI: 5.3% to 7.9%) of patients randomised to outreach and 3.3% (95% CI: 2.4% to 4.3%) of those randomised to usual care (OR 2.05, 95% CI: 1.44 to 2.92). The intervention increased HCC screening process completion across most subgroups including age, sex, race and ethnicity, Child-Turcotte-Pugh class and health system. PTC was also significantly higher in the outreach arm than usual care (mean 37.5% vs 28.2%; RR 1.33, 95% CI: 1.31 to 1.35). Despite screening underuse, most HCC in both arms were detected at an early stage.ConclusionMailed outreach plus navigation significantly increased HCC screening process completion versus usual care in patients with cirrhosis, with a consistent effect across most examined subgroups. However, screening completion remained suboptimal in both arms, underscoring a need for more intensive interventions.Trial registration numberNCT02582918.
Disentangling the relationship between social cognition, executive functions and behaviour changes in amyotrophic lateral sclerosis
Authors: Palumbo Francesca , Iazzolino Barbara , Callegaro Stefano , Canosa Antonio , Manera Umberto , Vasta Rosario , Grassano Maurizio , Matteoni Enrico , Cabras Sara , Pellegrino Giorgio , Salamone Paolina , Peotta Laura , Casale Federico , Fuda Giuseppe , Moglia Cristina , Chio Adriano , Calvo Andrea 
Published: June 2024

BackgroundSocial cognition (SC) deficits are included in the amyotrophic lateral sclerosis-frontotemporal spectrum disorder (ALS-FTDS) revised diagnostic criteria. However, the impact of SC assessment on cognitive classification and the cognitive–behavioural correlates of SC remain unclear. This cross-sectional study aimed to assess the impact of SC assessment on ALS-FTDS categorisation and explore the relationship of SC with executive functions (EF) and behaviour changes in a cohort of ALS patients.Methods121 patients and 56 healthy controls from the Turin ALS Centre underwent cognitive/behavioural testing, including the SC subdomains of facial emotion recognition, and cognitive and affective theory of mind (ToM).ResultsPatients performed significantly worse than controls in all SC explored domains, and 45% of patients exhibited a deficit in at least one SC test, dissociated from the presence of EF deficits. In 13% of cases, the SC deficit was isolated and subclinical. SC assessment contributed to the attribution of cognitive impairment in 10% of patients. Through a statistical clustering approach, we found that ToM only partially overlaps with EF while behaviour changes are associated with emotional disorders (anxiety and depression).ConclusionsSC is overall independent of EF in ALS, with ToM only partially associated with specific EF measures, and behaviour changes associated with emotional disorders. The influence of SC on cognitive categorisation and the frequent identification of a subclinical SC impairment have implications in a clinical setting, considering the substantial impact of cognitive impairment on disease burden and therapeutic choices.
Decoding AI in Contemporary Art: A Five-Trope Classification for Understanding and Categorization
Authors: Salimbeni Guido , Benford Steve , Reeves Stuart , Martindale Sarah 
Published: June 2024

Abstract
The article presents a historical overview of the classification of contemporary artworks that either have utilized artificial intelligence as a tool in their creation or focus on AI as their central theme or subject matter. The authors analyze artworks and descriptions, focusing on artists’ motivations and AI’s role in their practice, identifying five distinct tropes in AI art. The authors compare artworks with respect to key questions, creating a useful tool for art historians, curators, researchers, and artists. This historical classification provides a structured approach to understanding AI art’s creative significance and attributes as it has developed over time.
Contextualizing Polarimetric Retrievals of Boundary Layer Height Using State-of-the-Art Boundary Layer Profiling
Authors: Carlin Jacob T. , Smith Elizabeth N. , Giannakopoulos Katherine 
Published: June 2024

Abstract
Knowledge about the depth of the planetary boundary layer (PBL) is crucial for a variety of applications, but direct observations of PBL depth are spatiotemporally sparse. Recent studies have proposed using operational dual-polarization weather radars to observe the evolution of PBL depth by capitalizing on unique differential reflectivity (ZDR) signatures of Bragg scatter at the top of the PBL. While this approach appears promising and cost-effective, uncertainties remain about the representativeness of these estimates and how its efficacy may vary by geography and climatology. To address these outstanding uncertainties, this study compares collocated observations collected from two WSR-88D radars and two state-of-the-art mobile boundary layer profiling systems and evaluates the proposed methodology over the full diurnal cycle. Results indicate good overall correspondence between the profiling- and radar-based PBL depth estimates, with an abrupt divergence during the early evening transition and large discrepancies overnight. Relatively large root-mean-square-deviations (RMSDs) coupled with small biases match expectations when comparing spatially averaged data with point observations during PBL growth, which capture frequent fluctuations. A qualitative examination of the radar data reveals signatures of elevated residual layers, clouds, and ground clutter, all of which can obfuscate the desired surface-based PBL signal but which may have their own utility. The prominence of the Bragg scatter signal is found to be correlated with the observed moisture gradient at the top of the PBL, reflecting climatological variability that should be considered. These findings motivate further work to improve the automated detection of Bragg scatter layers from polarimetric radar data.

Significance Statement
Knowledge of the height of the planetary boundary layer matters for weather forecasting, air quality, and renewable energy production. Currently, boundary layer height measurements are taken at select locations twice a day. However, a method to use the existing national network of polarimetric weather radars for this purpose has been proposed. This work evaluates this method against specialized boundary layer measurements. The results show that the method is generally reliable during the daytime and could be used for a variety of applications including climatologies and model evaluation. There remain a number of situational caveats, including residual turbulence, clouds/precipitation, ground clutter, and certain meteorological environments, that may require modification of the approach and need to be considered in future work.