bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coxsackievirus group B3 regulates ASS1-mediated metabolic reprogramming and promotes macrophage inflammatory polarization in viral myocarditis
Authors: Liu Qiong , Shang Yinpan , Tao Ziwei , Li Xuan , Shen Lu , Zhang Hanchi , Liu Zhili , Rao Zhirong , Yu Xiaomin , Cao Yanli , Zeng Lingbing , Huang Xiaotian 
Published: August 2024

ABSTRACT

Coxsackievirus group B3 (CVB3) belongs to the genus
Enteroviruses
of the family
Picornaviridae
and is the main pathogen underlying viral myocarditis (VMC). No specific therapeutic is available for this condition. Argininosuccinate synthase 1 (ASS1) is a key enzyme in the urea cycle that converts citrulline and aspartic acid to argininosuccinate. Here, we found that CVB3 and its capsid protein VP2 inhibit the autophagic degradation of ASS1 and that CVB3 consumes citrulline to upregulate ASS1, triggers urea cycle metabolic reprogramming, and then activates macrophages to develop pro-inflammatory polarization, thereby promoting the occurrence and development of VMC. Conversely, citrulline supplementation to prevent depletion can downregulate ASS1, rescue macrophage polarization, and alleviate the pathogenicity of VMC. These findings provide a new perspective on the occurrence and development of VMC, revealing ASS1 as a potential new target for treating this disease.

IMPORTANCE
Viral myocarditis (VMC) is a common and potentially life-threatening myocardial inflammatory disease, most commonly caused by CVB3 infection. So far, the pathogenesis of VMC caused by CVB3 is mainly focused on two aspects: one is the direct myocardial injury caused by a large number of viral replication in the early stage of infection, and the other is the local immune cell infiltration and inflammatory damage of the myocardium in the adaptive immune response stage. There are few studies on the early innate immunity of CVB3 infection in myocardial tissue, but the appearance of macrophages in the early stage of CVB3 infection suggests that they can play a regulatory role as early innate immune response cells in myocardial tissue. Here, we discovered a possible new mechanism of VMC caused by CVB3, revealed new drug targets for anti-CVB3, and discovered the therapeutic potential of citrulline for VMC.
Requirement of the N-terminal region of nonstructural protein 1 in cis for SARS-CoV-2 defective RNA replication
Authors: Terasaki Kaori , Makino Shinji 
Published: August 2024

ABSTRACT

SARS-CoV-2 belongs to the family
Coronaviridae
and carries a single-stranded positive-sense RNA genome. During coronavirus (CoV) replication, defective or defective interfering RNAs that lack a large portion of the genome often emerge. These defective RNAs typically carry the necessary RNA elements that are required for replication and packaging. We identified the minimum requirement of the 5′ proximal region necessary for viral RNA replication by using artificially generated SARS-CoV-2 minigenomes. The minigenomes consist of the 5′-proximal region, an open reading frame (ORF) that encodes a fusion protein consisting of the N-terminal of viral NSP1 and a reporter gene, and the 3′ untranslated region of the SARS-CoV-2 genome. We used a modified SARS-CoV-2 variant to support replication of the minigenomes. A minigenome carrying the 5′ proximal 634 nucleotides replicated, whereas those carrying shorter than 634 nucleotides did not, demonstrating that the entire 265 nt-long 5′ untranslated region and N-terminal portion of the NSP1 coding region are required for the minigenome replication. Minigenome RNAs carrying a specific amino acid substitution or frame shift insertions in the partial NSP1 coding sequence abrogated minigenome replication. Introduction of synonymous mutations in the minigenome RNAs also affected the replication efficiency of the minigenomes. These data suggest that the expression of the N-terminal portion of NSP1 and the primary sequence of the 5′ proximal 634 nucleotides are important for minigenome replication.

IMPORTANCE
SARS-CoV-2, the causative agent of COVID-19, is highly transmissible and continues to have a significant impact on public health and the global economy. While several vaccines mitigate the severe consequences of SARS-CoV-2 infection, mutant viruses with reduced reactivity to current vaccines continue to emerge and circulate. This study aimed to identify the minimal 5′ proximal region of SARS-CoV-2 genomic RNA required for SARS-CoV-2 defective RNA replication and investigate the importance of an ORF encoded in these defective RNAs. Identifying cis-acting replication signals of SARS-CoV-2 genomic RNA is critical for the development of antivirals that target these signals. Additionally, replication-competent defective RNAs can serve as therapeutic reagents to interfere with SARS-CoV-2 replication. Our findings provide valuable insights into the mechanisms of SARS-CoV-2 RNA replication and the development of reagents that suppress SARS-CoV-2 replication.
Liquid-liquid phase separation is essential for reovirus viroplasm formation and immune evasion
Authors: He Libo , Wang Qian , Wang Xuyang , Zhou Fang , Yang Cheng , Li Yongming , Liao Lanjie , Zhu Zuoyan , Ke Fei , Wang Yaping 
Published: August 2024

ABSTRACT

Grass carp reovirus (GCRV) is the most virulent pathogen in the genus
Aquareovirus
, belonging to the family
Spinareoviridae
. Members of the
Spinareoviridae
family are known to replicate and assemble in cytoplasmic inclusion bodies termed viroplasms; however, the detailed mechanism underlying GCRV viroplasm formation and its specific roles in virus infection remains largely unknown. Here, we demonstrate that GCRV viroplasms form through liquid-liquid phase separation (LLPS) of the nonstructural protein NS80 and elucidate the specific role of LLPS during reovirus infection and immune evasion. We observe that viroplasms coalesce within the cytoplasm of GCRV-infected cells. Immunofluorescence and transmission electron microscopy indicate that GCRV viroplasms are membraneless structures. Live-cell imaging and fluorescence recovery after photobleaching assay reveal that GCRV viroplasms exhibit liquid-like properties and are highly dynamic structures undergoing fusion and fission. Furthermore, by using a reagent to inhibit the LLPS process and constructing an NS80 mutant defective in LLPS, we confirm that the liquid-like properties of viroplasms are essential for recruiting viral dsRNA, viral RdRp, and viral proteins to participate in viral genome replication and virion assembly, as well as for sequestering host antiviral factors for immune evasion. Collectively, our findings provide detailed insights into reovirus viroplasm formation and reveal the specific functions of LLPS during virus infection and immune evasion, identifying potential targets for the prevention and control of this virus.

IMPORTANCE
Grass carp reovirus (GCRV) poses a significant threat to the aquaculture industry, particularly in China, where grass carp is a vital commercial fish species. However, detailed information regarding how GCRV viroplasms form and their specific roles in GCRV infection remains largely unknown. We discovered that GCRV viroplasms exhibit liquid-like properties and are formed through a physico-chemical biological phenomenon known as liquid-liquid phase separation (LLPS), primarily driven by the nonstructural protein NS80. Furthermore, we confirmed that the liquid-like properties of viroplasms are essential for virus replication, assembly, and immune evasion. Our study not only contributes to a deeper understanding of GCRV infection but also sheds light on broader aspects of viroplasm biology. Given that viroplasms are a universal feature of reovirus infection, inhibiting LLPS and then blocking viroplasms formation may serve as a potential pan-reovirus inhibition strategy.
Chlamydia trachomatis
modulates the expression of JAK-STAT signaling components to attenuate the type II interferon response of epithelial cells
Authors: Fontanilla Francis L. , Ibana Joyce A. , Carabeo Rey A. , Brinkworth Amanda J. 
Published: August 2024

ABSTRACT

Chlamydia trachomatis
has adapted to subvert signaling in epithelial cells to ensure successful intracellular development. Interferon-γ (IFNγ) produced by recruited lymphocytes signals through the JAK/STAT pathway to restrict chlamydial growth in the genital tract. However, during
Chlamydia
infection
in vitro
, addition of IFNγ does not fully induce nuclear localization of its transcription factor STAT1 and expression of its target gene, IDO1. We hypothesize that this altered interferon response is a result of
Chlamydia
targeting components of the IFNγ-JAK/STAT pathway. To assess the ability of replicating
Chlamydia
to dampen interferon signaling, HEp2 human epithelial cells were infected with
C. trachomatis
serovar L2 for 24 hours prior to exposure to physiologically relevant levels of IFNγ (500 pg/mL). This novel approach enabled us to observe reduced phospho-activation of both STAT1 and its kinase Janus Kinase 2 (JAK2) in infected cells compared with mock-infected cells. Importantly, basal JAK2 and STAT1 transcript and protein levels were dampened by infection even in the absence of interferon, which could have implications for cytokine signaling beyond IFNγ. Additionally, target genes IRF1, GBP1, APOL3, IDO1, and SOCS1 were not fully induced in response to IFNγ exposure. Infection-dependent decreases in transcript, protein, and phosphoprotein were rescued when
de novo
bacterial protein synthesis was inhibited with chloramphenicol, restoring expression of IFNγ-target genes. Similar
Chlamydia
-dependent dampening of STAT1 and JAK2 transcript levels was observed in infected HeLa and END1 endocervical cells and in HEp2s infected with
C. trachomatis
serovar D, suggesting a conserved mechanism of dampening the interferon response by reducing the availability of key signaling components.

IMPORTANCE

As an obligate intracellular pathogen that has evolved to infect the genital epithelium,
Chlamydia
has developed strategies to prevent detection and antimicrobial signaling in its host to ensure its survival and spread. A major player in clearing
Chlamydia
infections is the inflammatory cytokine interferon-γ (IFNγ), which is produced by immune cells that are recruited to the site of infection. Reports of IFNγ levels in endocervical specimens from
Chlamydia
-infected patients range from 1 to 350 pg/mL, while most
in vitro
studies of the effects of IFNγ on chlamydial growth have used 15–85-fold higher concentrations. By using physiologically relevant concentrations of IFNγ, we were able to assess
Chlamydia
’s ability to modulate its signaling. We found that
Chlamydia
decreases the expression of multiple components that are required for inducing gene expression by IFNγ, providing a possible mechanism by which
Chlamydia trachomatis
can attenuate the immune response in the female genital tract to cause long-term infections.
Draft genome of
Thermoanaerobacter thermohydrosulfuricus
strain AK152, a novel thermophilic and anaerobic bacterium isolated from a hot spring in Iceland
Authors: Abraham Clay A. , Bradley Kevin M. , Scully Sean Michael , Orlygsson Johann , Dube Derek , Benner Steven A. 
Published: August 2024

ABSTRACT

We present the draft genome of the bacterium
Thermoanaerobacter thermohydrosulfuricus
strain AK152, a thermophilic, endospore–spore-forming, anaerobe isolated from a hot spring in Grensdalur, in Southwestern Iceland. This assembled genome will lay the foundation for identifying the carboxylic and amino acid fermentation pathways, suggesting biotechnological applications for this strain.
Late Cretaceous – Early Tertiary Deformation, North Greenland
Authors: soper N.J. , Higgins A.K. 
Published: August 2024

Abstract
Northern Greenland underwent within-plate deformations in Tertiary time in response to a rather complex and incompletely understood displacement history associated with the opening of Labrador Sea – Baffin Bay, the Arctic Ocean basins, and the North Atlantic. Because post-Ellesmerian cover sequences are not widely preserved in the region, it is frequently difficult to differentiate these “Eurekan” structures from earlier deformations, or to establish their precise age. Nonetheless, three sets of structures and two geotectonically important magmatic events of Cretaceous-Paleogene age have been recognized Fig. 16.1. Since these have been subject to speculative and often conflicting geotectonic interpretations, in this account we concentrate on the available factual information, following the review by Soper et al. (1982) and references therein, plus new information derived from 1984 fieldwork. We allude briefly to geotectonic implications, referring the reader to the Nares Strait symposium volume (Dawes and Kerr, 1982) for fuller discussion.
A dense swarm of approximately north-south trending (coast-normal) dolerite dykes occurs along the north coast of Greenland between about 38°W and 48°W (Nansen Land, westernmost Johannes V. Jensen Land and the intervening islands). Scattered examples are also present throughout Johannes V. Jensen Land. The swarm is most dense at sea level, approaching 50 per cent of the rock in places, with individual dykes up to 25 m in width and occasionally much larger. Dyke density diminishes both upward and to the south, the swarm being confined to the region north of the Harder Fjord fault zone (see below). The dykes cut lower Paleozoic
MYC Induces Oncogenic Stress through RNA Decay and Ribonucleotide Catabolism in Breast Cancer
Authors: Meena Jitendra K. , Wang Jarey H. , Neill Nicholas J. , Keough Dianne , Putluri Nagireddy , Katsonis Panagiotis , Koire Amanda M. , Lee Hyemin , Bowling Elizabeth A. , Tyagi Siddhartha , Orellana Mayra , Dominguez-Vidaña Rocio , Li Heyuan , Eagle Kenneth , Danan Charles , Chung Hsiang-Ching , Yang Andrew D. , Wu William , Kurley Sarah J. , Ho Brian M. , Zoeller Joseph R. , Olson Calla M. , Meerbrey Kristen L. , Lichtarge Olivier , Sreekumar Arun , Dacso Clifford C. , Guddat Luke W. , Rejman Dominik , Hocková Dana , Janeba Zlatko , Simon Lukas M. , Lin Charles Y. , Pillon Monica C. , Westbrook Thomas F. 
Published: August 2024

Abstract
Upregulation of MYC is a hallmark of cancer, wherein MYC drives oncogenic gene expression and elevates total RNA synthesis across cancer cell transcriptomes. Although this transcriptional anabolism fuels cancer growth and survival, the consequences and metabolic stresses induced by excess cellular RNA are poorly understood. Herein, we discover that RNA degradation and downstream ribonucleotide catabolism is a novel mechanism of MYC-induced cancer cell death. Combining genetics and metabolomics, we find that MYC increases RNA decay through the cytoplasmic exosome, resulting in the accumulation of cytotoxic RNA catabolites and reactive oxygen species. Notably, tumor-derived exosome mutations abrogate MYC-induced cell death, suggesting excess RNA decay may be toxic to human cancers. In agreement, purine salvage acts as a compensatory pathway that mitigates MYC-induced ribonucleotide catabolism, and inhibitors of purine salvage impair MYC+ tumor progression. Together, these data suggest that MYC-induced RNA decay is an oncogenic stress that can be exploited therapeutically.
Significance: MYC is the most common oncogenic driver of poor-prognosis cancers but has been recalcitrant to therapeutic inhibition. We discovered a new vulnerability in MYC+ cancer where MYC induces cell death through excess RNA decay. Therapeutics that exacerbate downstream ribonucleotide catabolism provide a therapeutically tractable approach to TNBC (Triple-negative Breast Cancer) and other MYC-driven cancers.
Intercorrências do tempo no Brasil moderno
Authors: Tavolaro Sergio B. F. 
Published: August 2024

While concerned with the conceptions of time that orient the portraits of the Brazilian social life outlined in the inaugural editions of História econômica do Brasil and Sobrados e mucambos, the article examines two hypotheses: first and foremost, despite the specificity of their approaches, the essays rest on a common epistemological ground that constrains Gilberto Freyre’s and Caio Prado Jr’s perceptions about Brazil’s societal formation as well as its place and prospects in the modern scene. Secondly, notwithstanding the critical intentions of these authors, both remain entrenched in the cognitive horizons of a hegemonic frame of reference on modernity, which ultimately leads Prado Jr and Freyre to ratify the longstanding idea of Brazil as a secondary and delayed experience vis-à-vis the so-called advanced modern societies.
Whole-Heart Histological and Electroanatomic Assessment of Postinfarction Cardiac Magnetic Resonance Imaging Scar and Conducting Channels
Authors: De Silva Kasun , Campbell Timothy , Bennett Richard G. , Anderson Robert D. , Davey Chris , O’Donohue Alexandra K. , Schindeler Aaron , Turnbull Samual , Selvakumar Dinesh , Bhaskaran Ashwin , Kotake Yasuhito , Hsu Chi-jen , Chong James J.H. , Kizana Eddy , Kumar Saurabh 
Published: August 2024

BACKGROUND:
Cardiac magnetic resonance imaging (CMR)–defined ventricular scar and anatomic conduction channels (CMR-CCs) offer promise in delineating ventricular tachycardia substrate. No studies have validated channels with coregistered histology, nor have they ascertained the histological characteristics of deceleration zones (DZs) within these channels. We aimed to validate CMR scar and CMR-CCs with whole-heart histology and electroanatomic mapping in a postinfarction model.

METHODS:
Five sheep underwent anteroseptal infarction. CMR (116±20 days post infarct) was postprocessed using ADAS-3D, varying pixel intensity thresholds (5545, 6040, 6535, and 7030). DZs were identified by electroanatomic mapping (129±12 days post infarct). Explanted hearts were sectioned and stained with Picrosirius red, and whole-heart histopathologic shells were generated. Scar topography as well as percentage fibrosis, adiposity, and remaining viable myocardium within 3 mm histological biopsies and within CMR-CCs were determined.

RESULTS:

Using the standard 6040 thresholding, CMR had 83.8% accuracy for identifying histological scar in the endocardium (κ, 0.666) and 61.4% in the epicardium (κ, 0.276). Thirty-seven CMR-CCs were identified by varying thresholding; 23 (62%) were unique. DZs colocalized to 19 of 23 (83%) CMR-CCs. Twenty (87%) CMR-CCs were histologically confirmed. Within-channel histological fibrosis did not differ by the presence of DZs (
P
=0.242). Within-channel histological adiposity was significantly higher at sites with versus without DZs (24.1% versus 8.3%;
P
<0.001).

CONCLUSIONS:
Postprocessed CMR-derived scars and channels were validated by histology and electroanatomic mapping. Regions of CMR-CCs at sites of DZs had higher adiposity but similar fibrosis than regions without DZs, suggesting that lipomatous metaplasia may contribute to arrhythmogenicity of postinfarction scar.
Outcomes of Atrial Fibrillation Ablation in Heart Failure Subtypes
Authors: Younis Arwa , Tabaja Chadi , Santangeli Pasquale , Nakagawa Hiroshi , Sipko Joseph , Madden Ruth , Bouscher Patricia , Taigen Tyler , Higuchi Koji , Hayashi Katsuhide , El Hajjar Abdel Hadi , Chamseddine Fatimah , Callahan Thomas , Martin David O. , Nakhla Shady , Kanj Mohamed , Sroubek Jakub , Lee Justin Z. , Saliba Walid I. , Wazni Oussama M. , Hussein Ayman A. 
Published: August 2024

BACKGROUND:
Catheter ablation (CA) improves clinical outcomes in patients with atrial fibrillation (AF) and heart failure (HF) with reduced ejection fraction (HFrEF). We aimed to evaluate the impact of CA on clinical and quality-of-life outcomes across HF subtypes.

METHODS:
All patients undergoing AF ablation at a tertiary center were enrolled in a prospective registry and included in this study (2013–2021). The primary end point was AF recurrence. Secondary end points included AF-related hospitalizations and quality-of-life outcomes. Patients were categorized according to their HF status: no HF, HFrEF, HF with mildly reduced ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF).

RESULTS:

A total of 7020 patients were included (80% no HF, 8% HFrEF, 7% HFmrEF, and 5% HFpEF). Over 3 years, the cumulative incidence of AF recurrence after ablation was as follows: HFpEF (53%), HFmrEF (41%), HFrEF (41%), and no HF (34%);
P
<0.01. Multivariable Cox analyses confirmed these findings using no HF group as reference (HFpEF: hazard ratio, 1.47 [95% CI, 1.21–1.78]; HFmrEF: hazard ratio, 1.23 [95% CI, 1.04–1.45]; and HFrEF: hazard ratio, 1.17 [95% CI, 1.01–1.37];
P
<0.05 for all). In all groups, CA resulted in a significant reduction of AF-related hospitalization (mean rate per 1 patient-years [before and after CA]; HFpEF [1.8 versus 0.3], HFmrEF [1.1 versus 0.2], HFrEF [1.1 versus 0.2], and no HF [1 versus 0.1];
P
<0.01 for each comparison) and significant improvement in quality of life as measured by both the AF symptom severity score and the AF burden score (
P
<0.01 for the comparison between baseline and follow-up for each score when tested separately).

CONCLUSIONS:
AF recurrence rates after CA were higher in patients with HF compared with those without HF, with patients with HFpEF being at the highest risk of recurrence. Nonetheless, CA was associated with a significant reduction in AF symptoms, AF-related hospitalization, and HF symptoms in most patients irrespective of HF subtypes.
Volatile compounds and quality changes of lesser mealworm larvae: effect of blanching, storage temperature and time
Authors: Yener S. , Mishyna M. , Zhao L. , Velazco O.N. , Cadesky L. , Lakemond C. , Fogliano V. 
Published: August 2024

Abstract
The impact of blanching and storage temperature (−20 °C and −80 °C) on the formation of volatile organic compounds and changes in quality characteristics of lesser mealworm (Alphitobius diaperinus) larvae was examined over seven weeks. Acid and peroxide values, pH, and colour of lesser mealworm larvae were significantly affected by the studied variables. The changes in these characteristics as well as in the volatile profile indicated occurring lipid oxidation and lipid hydrolysis processes during the storage. The intensity of these reactions was mostly influenced by blanching treatment and storage time, and a lesser extent by storage temperature. It was proposed that changes in composition and intensity of volatiles can be used for rapid quality assessment of lesser mealworm larvae during frozen storage. Thus, the selection of optimum storage conditions for lesser mealworm larvae is important for the prevention of undesirable chemical reactions and preservation of the quality of insect biomass.