bluuebunny/crossref_metadata_2025_split huggingface dataset:
3β-hydroxysteroid-Δ24 reductase dampens anti-viral innate immune responses by targeting K27 ubiquitination of MAVS and STING
Authors: Liu Qian , Chen Shengwen , Tian Renyun , Xue Binbin , Li Huiyi , Guo Mengmeng , Liu Shun , Yan Ming , You Ruina , Wang Luoling , Yang Di , Wan Mengyu , Zhu Haizhen 
Published: November 2023

ABSTRACT
The mechanism by which lipid metabolism regulates innate immunity is unknown. Here, we report that the key enzyme in cholesterol synthesis, 3β-hydroxysteroid-Δ24 reductase (DHCR24), is inhibited by viral infection. DHCR24 deficiency significantly promotes interferon production and interferon-stimulated gene expression. Inhibition of DHCR24 enzyme activity or the addition of the precursor 24-dehydrocholesterol (24-DHC) can augment innate immunity. Mechanistically, DHCR24 interacts with MAVS or STING, and DHCR24 impairs K27-linked ubiquitination of MAVS mediated by TRIM21 and K27-linked ubiquitination of STING mediated by AMFR, blocking the activation of MAVS and STING, respectively. Collectively, DHCR24 plays a negative role in regulating innate immune responses that may be targeted to improve immunity.

IMPORTANCE
The precise regulation of the innate immune response is essential for the maintenance of homeostasis. MAVS and STING play key roles in immune signaling pathways activated by RNA and DNA viruses, respectively. Here, we showed that DHCR24 impaired the antiviral response by targeting MAVS and STING. Notably, DHCR24 interacts with MAVS and STING and inhibits TRIM21-triggered K27-linked ubiquitination of MAVS and AMFR-triggered K27-linked ubiquitination of STING, restraining the activation of MAVS and STING, respectively. Together, this study elucidates how one cholesterol key enzyme orchestrates two antiviral signal transduction pathways.
Amino acid substitutions in norovirus VP1 dictate host dissemination via variations in cellular attachment
Authors: Mills Jake T. , Minogue Susanna C. , Snowden Joseph S. , Arden Wynter K. C. , Rowlands David J. , Stonehouse Nicola J. , Wobus Christiane E. , Herod Morgan R. 
Published: November 2023

ABSTRACT

Viruses interact with receptors on the cell surface to initiate and coordinate infection. The distribution of receptors on host cells can be a key determinant of viral tropism and host infection. Unravelling the complex nature of virus-receptor interactions is, therefore, of fundamental importance to understanding viral pathogenesis. Noroviruses are non-enveloped, icosahedral, positive-sense RNA viruses of global importance to human health, with no approved vaccine or antiviral agent available. Here, we use murine norovirus as a model to study the molecular mechanisms of virus-receptor interactions. We show that variation at a single amino acid residue in the major viral capsid protein, VP1 301, has a key impact on the interaction between virus and receptor. This variation did not affect virion replication or virus growth kinetics, but a specific amino acid was rapidly selected through evolution experiments and significantly improved cellular attachment when infecting cells in suspension. However, modulating plasma membrane mobility counteracted this phenotype, suggesting a role for membrane fluidity in norovirus cellular attachment. When the infectivity of a panel of recombinant viruses with single amino acid substitutions at this residue was compared
in vivo
, there were differences in the tissue distribution of viruses in a murine host, suggesting a role for VP1 301 in dissemination
in vivo
. Overall, these results highlight how capsid evolution can influence infectivity and dissemination in the host.

IMPORTANCE
All viruses initiate infection by utilizing receptors to attach to target host cells. These virus-receptor interactions can therefore dictate viral replication and pathogenesis. Understanding the nature of virus-receptor interactions could also be important for the development of novel therapies. Noroviruses are non-enveloped icosahedral viruses of medical importance. They are a common cause of acute gastroenteritis with no approved vaccine or therapy and are a tractable model for studying fundamental virus biology. In this study, we utilized the murine norovirus model system to show that variation in a single amino acid of the major capsid protein alone can affect viral infectivity through improved attachment to suspension cells. Modulating plasma membrane mobility reduced infectivity, suggesting an importance of membrane mobility for receptor recruitment and/or receptor conformation. Furthermore, different substitutions at this site altered viral tissue distribution in a murine model, illustrating how in-host capsid evolution could influence viral infectivity and/or immune evasion.
A two-component system serves as a central hub for connecting energy metabolism and plasmid dissemination in bacteria
Authors: Kubori Tomoko 
Published: November 2023

ABSTRACT

Mobile genetic elements such as conjugative plasmids play a key role in the acquisition of antibiotic resistance by pathogenic bacteria. Resistance genes on plasmids can be transferred between bacteria using specialized conjugation machinery.
Acinetobacter baumannii
, the most common bacterium associated with nosocomial infections, harbors a large conjugative plasmid that encodes a type IV secretion system (T4SS). Feng et al. recently found that the
A. baumannii
T4SS is specialized for plasmid transfer, suggesting that it may be involved in multidrug resistance (Z. Feng, L. Wang, Q. Guan, X. Chu, and Z.-Q. Luo
,
mBio e02276-23, 2023,
https://doi.org/10.1128/mbio.02276-23
), T4SS-encoding genes are shown to be controlled by a versatile GacA/S two-component regulatory system. GacA/S is also found to regulate genes involved in central metabolism. The coordinated regulation of metabolism and plasmid conjugation may be a bacterial strategy for adapting to selective pressure from antibiotics.
Campylobacter jejuni
uses energy taxis and a dehydrogenase enzyme for
l
-fucose chemotaxis
Authors: Zhou Bibi , Garber Jolene M. , Vlach Jiri , Azadi Parastoo , Ng Kenneth K. S. , Escalante-Semerena Jorge C. , Szymanski Christine M. 
Published: November 2023

ABSTRACT

Campylobacter jejuni
is a leading cause of bacterial diarrhea worldwide, and infection in infants is associated with growth stunting in low- and middle-income countries. Approximately half of all
C. jejuni
isolates are asaccharolytic, while the remainder encode enzymes capable of
l
-fucose catabolism. Our previous study suggested that breastfed infants originating from sub-Saharan Africa and South Asia were colonized less frequently with
l
-fucose-metabolizing
C. jejuni
isolates compared to asaccharolytic strains. We also showed that FucX is an
l
-fucose dehydrogenase that binds to its NADP
+
cofactor even in the absence of
l
-fucose and that this enzyme is sufficient for
l
-fucose chemotaxis when introduced into strains lacking the metabolic pathway. This study indicates that FucX may influence
l
-fucose chemotaxis by increasing cellular NADPH/NADP
+
ratios, which subsequently affect the energy taxis components, CetABC that respond to shifting gradients of electron acceptors and donors. Furthermore,
C. jejuni
CetAB and CetAC can complement
Escherichia coli
aerotaxis. Our data support a model in which the shift in NADP
+
levels, impacted by the FucX dehydrogenase, affects chemotaxis in response to
l
-fucose. This swimming behavior can be phenocopied with a homologous
l
-fucose dehydrogenase from
Burkholderia multivorans
. Taken together, our work provides a possible explanation for why
l
-fucose-metabolizing
C. jejuni
isolates swim away from intestinal epithelial cells toward free fucose in the lumen where they are subsequently cleared by breastfed infants.

IMPORTANCE

In this study, we identify a separate role for the
Campylobacter jejuni
l
-fucose dehydrogenase in
l
-fucose chemotaxis and demonstrate that this mechanism is not only limited to
C. jejuni
but is also present in
Burkholderia multivorans
. We now hypothesize that
l
-fucose energy taxis may contribute to the reduction of
l
-fucose-metabolizing strains of
C. jejuni
from the gastrointestinal tract of breastfed infants, selecting for isolates with increased colonization potential.
Relationships among Development, Growth, Body Size, Reproduction, Aging, and Longevity – Trade-Offs and Pace-Of-Life
Authors: Yuan Rong , Hascup Erin , Hascup Kevin , Bartke Andrzej 
Published: November 2023

Abstract
Relationships of growth, metabolism, reproduction, and body size to the biological process of aging and longevity have been studied for decades and various unifying “theories of aging” have been proposed to account for the observed associations. In general, fast development, early sexual maturation leading to early reproductive effort, as well as production of many offspring, have been linked to shorter lifespans. The relationship of adult body size to longevity includes a remarkable contrast between the positive correlation in comparisons between different species and the negative correlation seen in comparisons of individuals within the same species. We now propose that longevity and presumably also the rate of aging are related to the “pace-of-life.” A slow pace-of-life including slow growth, late sexual maturation, and a small number of offspring, predicts slow aging and long life. The fast pace of life (rapid growth, early sexual maturation, and major reproductive effort) is associated with faster aging and shorter life, presumably due to underlying trade-offs. The proposed relationships between the pace-of-life and longevity apply to both inter- and intra-species comparisons as well as to dietary, genetic, and pharmacological interventions that extend life and to evidence for early life programming of the trajectory of aging. Although available evidence suggests the causality of at least some of these associations, much further work will be needed to verify this interpretation and to identify mechanisms that are responsible.
Understanding the protective effect of social support on depression symptomatology from a longitudinal network perspective
Authors: Li Gen , Li Yifan , Lam Agnes Iok Fong , Tang Weiming , Seedat Soraya , Barbui Corrado , Papola Davide , Panter-Brick Catherine , Waerden Judith van der , Bryant Richard , Mittendorfer-Rutz Ellenor , Gémes Katalin , Purba Fredrick D , Setyowibowo Hari , Pinucci Irene , Palantza Christina , Acarturk Ceren , Kurt Gülşah , Tarsitani Lorenzo , Morina Naser , Burchert Sebastian , Patanè Martina , Quero Soledad , Campos Daniel , Huizink Anja C , Fuhr Daniela C , Spiller Tobias , Sijbrandij Marit , Hall Brian J 
Published: November 2023

BackgroundHigher social support protects people from developing mental disorders. Limited evidence is available on the mechanism through which social support plays this protective role.ObjectiveTo investigate the stress-buffering process of social support on depressive symptoms using a novel longitudinal dynamic symptom network approach.MethodsA total of 4242 adult participants who completed the first two waves (from May to October 2020) of the International Covid Mental Health Survey were included in the study. Cross-lagged panel network modelling was used to estimate a longitudinal network of self-reported social support, loneliness and depressive symptoms. Standardised regression coefficients from regularised cross-lagged regressions were estimated as edge weights of the network.FindingsThe results support a unidirectional protective effect of social support on key depressive symptoms, partly mediated through loneliness: A highernumber of close confidantsandaccessible practical helpwas associated with decreasedanhedonia(weight=−0.033) andnegative self-appraisalsymptoms (weight=−0.038). Support from others was also negatively associated with loneliness, which in turn associated with decreaseddepressed mood(weight=0.086) andnegative self-appraisal(weight=0.077). We identified a greater number of direct relationships from social support to depressive symptoms among men compared with women. Also, the edge weights from social support to depression were generally stronger in the men’s network.ConclusionsReductions in negative self-appraisal might function as a bridge between social support and other depressive symptoms, and, thus, it may have amplified the protective effect of social support. Men appear to benefit more from social support than women.Clinical implicationsBuilding community-based support networks to deliver practical support, and loneliness reduction components are critical for depression prevention interventions after stressful experiences.
Development of a semi-cylindrical time projection chamber prototype for ($$^{3}{\textrm{He}},t$$) charge exchange reaction experiment
Authors: He Zhixuan , Li Meng , Bu Wenjuan , Xiao Chaoyuan , Wei Xianglun , Yang Yuansheng , Qin Zhi , He Shanhaowei , Qiu Tianli , Ma Peng , Lu Chengui , Duan Limin , Hu Bitao , Zhang Yi , Yang Herun 
Published: November 2023

AbstractThe charge exchange (CE) reaction is an effective probe to study the structure of atomic nuclei in the isospin dimension, which has been studied for decades. To expand the range of nuclei studied by CE reactions to a wider range and research the structure characteristics of unstable nuclei, including the isospin symmetry, spin-isospin excitation, and nuclear symmetry energy, a semi-cylindrical time projection chamber (scTPC) prototype was designed and constructed to probe ($$^{\textrm{3}}$$

3

He,t) CE reactions in inverse kinematics. The 266 nm UV laser was used to achieve electron-drift-velocity calibration. The scTPC has an energy resolution (FWHM) of 5.6% for $$\alpha $$
α
particles emitted by $$^{\textrm{241}}$$

241

Am radioactive source. The position resolution of scTPC is described by the residual method. The spatial resolution on the pad plane is 409 $$\upmu $$
μ
m. And the position resolution in the drift direction is 326 $$\upmu $$
μ
m, equivalent to an angular resolution of 0.4$$^\circ $$

∘

. These performances suggest that the scTPC can measure $$\Delta E $$

Δ
E

and particle tracks precisely. The successful development of the scTPC prototype provides better conditions for the next step of experimental data analysis and processing.
Anisotropic extension of Kohler–Chao–Tikekar solution by minimal geometric deformation
Authors: Andrade J. , Ortega K. Yanza , Klínger W. N. Ramírez , Copa R. C. Guadalupe , Medina S. S. Chicaiza , Cruz J. D. 
Published: November 2023

AbstractThis work is devoted to transforming the known cosmological solution of Kohler–Chao–Tikekar into an anisotropic interior solution using the framework of Gravitational Decoupling by minimal geometric deformation. The resulting interior solution fulfils the fundamental physical acceptability stellar conditions for a specific set of compactness factors. The stability of the model is also investigated.
Revisiting the scalar leptoquark $$(S_1)$$ model with the updated leptonic constraints
Authors: De Bibhabasu 
Published: November 2023

AbstractThe Standard Model, if extended to the energy scale of $${\mathscr {O}}(1)$$

O
(
1
)

TeV, the known particle spectrum could be augmented with a scalar leptoquark. Within this minimally extended framework, explaining the anomalous magnetic moment and electric dipole moment simultaneously for the three lepton generations over a parameter space consistent with all the lepton flavor violating bounds is possible. Such a model can be tested or falsified through the collider search experiments and/or by probing the low-energy lepton phenomena. This work studies the current prospects of the model in the presence of recent experimental updates for the leptonic observables.
SHP2 Inhibition with TNO155 Increases Efficacy and Overcomes Resistance of ALK Inhibitors in Neuroblastoma
Authors: Valencia-Sama Ivette , Kee Lynn , Christopher Gabriella , Ohh Michael , Layeghifard Mehdi , Shlien Adam , Hayes Madeline N. , Irwin Meredith S. 
Published: November 2023

AbstractSurvival rates among patients with high-risk neuroblastoma remain low and novel therapies for recurrent neuroblastomas are required. ALK is commonly mutated in primary and relapsed neuroblastoma tumors and ALK tyrosine kinase inhibitors (TKI) are promising treatments for ALK-driven neuroblastoma; however, innate or adaptive resistance to single-agent ALK-TKIs remain a clinical challenge. Recently, SHP2 inhibitors have been shown to overcome ALK-TKI resistance in lung tumors harboring ALK rearrangements. Here, we have assessed the efficacy of the SHP2 inhibitor TNO155 alone and in combination with the ALK-TKIs crizotinib, ceritinib, or lorlatinib for the treatment of ALK-driven neuroblastoma using in vitro and in vivo models. In comparison to wild-type, ALK-mutant neuroblastoma cell lines were more sensitive to SHP2 inhibition with TNO155. Moreover, treatment with TNO155 and ALK-TKIs synergistically reduced cell growth and promoted inactivation of ALK and MAPK signaling in ALK-mutant neuroblastoma cells. ALK-mutant cells engrafted into larval zebrafish and treated with single agents or dual SHP2/ALK inhibitors showed reduced growth and invasion. In murine ALK-mutant xenografts, tumor growth was likewise reduced or delayed, and survival was prolonged upon combinatorial treatment of TNO155 and lorlatinib. Finally, we show that lorlatinib-resistant ALK-F1174L neuroblastoma cells harbor additional RAS-MAPK pathway alterations and can be resensitized to lorlatinib when combined with TNO155 in vitro and in vivo. Our results report the first evaluation of TNO155 in neuroblastoma and suggest that combinatorial inhibition of ALK and SHP2 could be a novel approach to treating ALK-driven neuroblastoma, potentially including the increasingly common tumors that have developed resistance to ALK-TKIs.Significance:These findings highlight the translatability between zebrafish and murine models, provide evidence of aberrant RAS-MAPK signaling as an adaptive mechanism of resistance to lorlatinib, and demonstrate the clinical potential for SHP2/ALK inhibitor combinations for the treatment of ALK-mutant neuroblastoma, including those with acquired tolerance or potentially resistance to ALK-TKIs.
FBXW7-loss Sensitizes Cells to ATR Inhibition Through Induced Mitotic Catastrophe
Authors: O'Brien Siobhan , Ubhi Tajinder , Wolf Lucie , Gandhi Krishna , Lin Sichun , Chaudary Naz , Dhani Neesha C. , Milosevic Michael , Brown Grant W. , Angers Stephane 
Published: November 2023

Abstract

FBXW7 is a commonly mutated tumor suppressor gene that functions to regulate numerous oncogenes involved in cell-cycle regulation. Genome-wide CRISPR fitness screens identified a signature of DNA repair and DNA damage response genes as required for the growth of FBXW7-knockout cells. Guided by these findings, we show that FBXW7-mutant cells have high levels of replication stress, which results in a genotype-specific vulnerability to inhibition of the ATR signaling pathway, as these mutant cells become heavily reliant on a robust S–G2 checkpoint. ATR inhibition induces an accelerated S-phase, leading to mitotic catastrophe and cell death caused by the high replication stress present in FBXW7−/− cells. In addition, we provide evidence in cell and organoid studies, and mining of publicly available high-throughput drug screening efforts, that this genotype-specific vulnerability extends to multiple types of cancer, providing a rational means of identifying responsive patients for targeted therapy.

Significance:
We have elucidated the synthetic lethal interactions between FBXW7 mutation and DNA damage response genes, and highlighted the potential of ATR inhibitors as targeted therapies for cancers harboring FBXW7 alterations.
Unraveling the Role of Sex in Endothelial Cell Dysfunction: Evidence From Lineage Tracing Mice and Cultured Cells
Authors: Shin Junchul , Hong Junyoung , Edwards-Glenn Jonnelle , Krukovets Irene , Tkachenko Svyatoslav , Adelus Maria L. , Romanoski Casey E. , Rajagopalan Sanjay , Podrez Eugene , Byzova Tatiana V. , Stenina-Adongravi Olga , Cherepanova Olga A. 
Published: November 2023

BACKGROUND:
Biological sex differences play a vital role in cardiovascular diseases, including atherosclerosis. The endothelium is a critical contributor to cardiovascular pathologies since endothelial cells (ECs) regulate vascular tone, redox balance, and inflammatory reactions. Although EC activation and dysfunction play an essential role in the early and late stages of atherosclerosis development, little is known about sex-dependent differences in EC.

METHODS:

We used human and mouse aortic EC as well as EC-lineage tracing (
Cdh5
-CreERT2 Rosa-YFP [yellow fluorescence protein]) atherosclerotic
Apoe

–/–

mice to investigate the biological sexual dimorphism of the EC functions in vitro and in vivo. Bioinformatics analyses were performed on male and female mouse aortic EC and human lung and aortic EC.

RESULTS:
In vitro, female human and mouse aortic ECs showed more apoptosis and higher cellular reactive oxygen species levels than male EC. In addition, female mouse aortic EC had lower mitochondrial membrane potential (ΔΨm), lower TFAM (mitochondrial transcription factor A) levels, and decreased angiogenic potential (tube formation, cell viability, and proliferation) compared with male mouse aortic EC. In vivo, female mice had significantly higher lipid accumulation within the aortas, impaired glucose tolerance, and lower endothelial-mediated vasorelaxation than males. Using the EC-lineage tracing approach, we found that female lesions had significantly lower rates of intraplaque neovascularization and endothelial-to-mesenchymal transition within advanced atherosclerotic lesions but higher incidents of missing EC lumen coverage and higher levels of oxidative products and apoptosis. RNA-seq analyses revealed that both mouse and human female EC had higher expression of genes associated with inflammation and apoptosis and lower expression of genes related to angiogenesis and oxidative phosphorylation than male EC.

CONCLUSIONS:
Our study delineates critical sex-specific differences in EC relevant to proinflammatory, pro-oxidant, and angiogenic characteristics, which are entirely consistent with a vulnerable phenotype in females. Our results provide a biological basis for sex-specific proatherosclerotic mechanisms.
Stempellinella Brundin, 1947 (Diptera: Chironomidae) from Eastern Siberia and the Russian Far East, with the description of new species
Authors: OREL OKSANA V. 
Published: November 2023

Two new species of the genus Stempellinella Brundin, 1947, S. bazovae sp. nov. and S. chirka sp. nov., from Eastern Siberia and the Russian Far East are described. Illustrated redescriptions of males for further three species, S. coronata Inoue, Kawai et Imabayashi, 2004, S. edwardsi Spies et Saether, 2004, S. tamaseptima (Sasa, 1980) are given. Stempellinella ministylus Ree, 2015 is a new synonym Stempellinella coronata Inoue, Kawai et Imabayashi, 2004. Key to the males and pupae of the Russian Far East and Eastern Siberia Stempellinella species is provided.