bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations Between Changes in 24-Hour Movement Behaviors in Children and Adolescents During the COVID-19 Pandemic: A Systematic Review and Mediation-Based Meta-Analysis
Authors: Neville Ross D. , Hopkins William G. , McArthur Brae Anne , Draper Catherine E. , Madigan Sheri 
Published: January 2024

Background: Although 24-hour movement behaviors are known to be interconnected, limited knowledge exists about whether change in one behavior during the COVID-19 pandemic (eg, increased screen time) was associated with change in another (eg, reduced physical activity or sleep). This review estimates mediational associations between changes in children’s physical activity, screen time, and sleep during the COVID-19 pandemic. Methods: We included studies published between January 1, 2020 and June 27, 2022, in the PubMed/MEDLINE, Embase, PsycINFO, SPORTDiscus, and Web of Science databases. Summary data were extracted from included studies and analyzed with random-effects meta-regression. Results: This review included 26 studies representing 18,959 children across 18 mid-high-income countries (53% male; mean age, 11.5 [2.9] y). There was very good evidence of decreased total daily physical activity (factor change, 0.62; 90% CI, 0.47–0.81) and strong evidence of increased screen time (1.56; 90% CI, 1.38–1.77). There was very good evidence of decreased moderate to vigorous physical activity (0.75; 90% CI, 0.62–0.90) and weak evidence of increased sleep (1.02; 90% CI, 1.00–1.04). Mediational analysis revealed strong evidence that most of the reduction in total daily physical activity from before, to during, the pandemic was associated with increased screen time (0.53; 90% CI, 0.42–0.67). We observed no further mediational associations. Conclusion: Increased reliance on and use of screen-based devices during the COVID-19 pandemic can be linked with reduced child and adolescent physical activity. This finding links COVID-related restrictions to potential displacement effects within child and adolescent 24-hour movement behavior.
A new ROS response factor YvmB protects
Bacillus licheniformis
against oxidative stress under adverse environment
Authors: He Penghui , Hu Shiying , Zhang Yongjia , Xiang Zhengwei , Zhang Zheng , Wang Dong , Chen Shouwen 
Published: January 2024

ABSTRACT

Bacillus
spp., a class of aerobic bacteria, is widely used as a biocontrol microbe in the world. However, the reactive oxygen species (ROS) will accumulate once the aerobic bacteria are exposed to environmental stresses, which can decrease cell activity or lead to cell death. Hydroxyl radical (·OH), the strongest oxide in the ROS, can damage DNA directly, which is generated through Fenton Reaction by H
2
O
2
and free iron. Here, we proved that the synthesis of pulcherriminic acid (PA), an iron chelator produced by
Bacillus
spp., could reduce DNA damage to protect cells from oxidative stress by sequestrating excess free iron, which enhanced the cell survival rates in stressful conditions (salt, antibiotic, and high temperature). It was worth noting that the synthesis of PA was found to be increased under oxidative stress. Thus, we demonstrated that the YvmB, a direct negative regulator of PA synthesis cluster
yvmC-cypX
, could be oxidized at cysteine residue (C57) to form a dimer losing the DNA-binding activity, which led to an improvement in PA production. Collectively, our findings highlight that YvmB senses ROS to regulate PA synthesis is one of the evolved proactive defense systems in bacteria against adverse environments.

IMPORTANCE

Under environment stress, the electron transfer chain will be perturbed resulting in the accumulation of H
2
O
2
and rapidly transform to ·OH through Fenton Reaction. How do bacteria deal with oxidative stress? At present, several iron chelators have been reported to decrease the ·OH generation by sequestrating iron, while how bacteria control the synthesis of iron chelators to resist oxidative stress is still unclear. Our study found that the synthesis of iron chelator PA is induced by reactive oxygen species (ROS), which means that the synthesis of iron chelator is a proactive defense mechanism against environment stress. Importantly, YvmB is the first response factor found to protect cells by reducing the ROS generation, which present a new perspective in antioxidation studies.
Seasonal influenza viruses decay more rapidly at intermediate humidity in droplets containing saliva compared to respiratory mucus
Authors: Rockey Nicole C. , Le Sage Valerie , Marr Linsey C. , Lakdawala Seema S. 
Published: January 2024

ABSTRACT

Expulsions of virus-laden aerosols or droplets from the oral and nasal cavities of an infected host are an important source of onward respiratory virus transmission. However, the presence of infectious influenza virus in the oral cavity during infection has not been widely considered, and thus, little work has explored the environmental persistence of influenza virus in oral cavity expulsions. Using the ferret model, we detected infectious virus in the nasal and oral cavities, suggesting that the virus can be expelled into the environment from both anatomical sites. We also assessed the stability of two influenza A viruses (H1N1 and H3N2) in droplets of human saliva or respiratory mucus over a range of relative humidities. We observed that influenza virus infectivity decays rapidly in saliva droplets at intermediate relative humidity, while viruses in airway surface liquid droplets retain infectivity. Virus inactivation was not associated with bulk protein content, salt content, or droplet drying time. Instead, we found that saliva droplets exhibited distinct inactivation kinetics during the wet and dry phases at intermediate relative humidity, and droplet residue morphology may lead to the elevated first-order inactivation rate observed during the dry phase. Additionally, distinct differences in crystalline structure and nanobead localization were observed between saliva and airway surface liquid droplets. Together, our work demonstrates that different respiratory fluids exhibit unique virus persistence profiles and suggests that influenza viruses expelled from the oral cavity may contribute to virus transmission in low- and high-humidity environments.

IMPORTANCE
Determining how long viruses persist in the environment is important for mitigating transmission risk. Expelled infectious droplets and aerosols are composed of respiratory fluids, including saliva and complex mucus mixtures, but how well influenza viruses survive in such fluids is largely unknown. Here, we find that infectious influenza virus is present in the oral cavity of infected ferrets, suggesting that saliva-containing expulsions can play a role in onward transmission. Additionally, influenza virus in droplets composed of saliva degrades more rapidly than virus within respiratory mucus. Droplet composition impacts the crystalline structure and virus localization in dried droplets. These results suggest that viruses from distinct sites in the respiratory tract could have variable persistence in the environment, which will impact viral transmission fitness.
IFN-λ3 is induced by
Leishmania donovani
and can inhibit parasite growth in cell line models but not in the mouse model, while it shows a significant association with leishmaniasis in humans
Authors: De Manjarika , Sukla Soumi , Bharatiya Seema , Keshri Sagar , Roy Debarati Guha , Roy Sutopa , Dutta Debrupa , Saha Shriya , Ejazi Sarfaraz Ahmad , Ravichandiran V. , Ali Nahid , Chatterjee Mitali , Chinnaswamy Sreedhar 
Published: January 2024

ABSTRACT

The intracellular protozoan parasite
Leishmania donovani
causes debilitating human diseases that involve visceral and dermal manifestations. Type 3 interferons (IFNs), also referred to as lambda IFNs (IFNL, IFN-L, or IFN-λ), are known to play protective roles against intracellular pathogens at the epithelial surfaces. Herein, we show that
L. donovani
induces IFN-λ3 in human as well as mouse cell line-derived macrophages. Interestingly, IFN-λ3 treatment significantly decreased parasite load in infected cells
,
mainly by increasing reactive oxygen species production. Microscopic examination showed that IFN-λ3 inhibited uptake but not replication, while the phagocytic ability of the cells was not affected. This was confirmed by experiments that showed that IFN-λ3 could decrease parasite load only when added to the medium at earlier time points, either during or soon after parasite uptake, but had no effect on parasite load when added at 24 h post-infection, suggesting that an early event during parasite uptake was targeted. Furthermore, the parasites could overcome the inhibitory effect of IFN-λ3, which was added at earlier time points, within 2-3 days post-infection. BALB/c mice treated with IFN-λ3 before infection led to a significant increase in expression of IL-4 and ARG1 post-infection in the spleen and liver, respectively, and to different pathological changes, especially in the liver, but not to changes in parasite load. Treatment with IFN-λ3 during infection did not decrease the parasite load in the spleen either. However, IFN-λ3 was significantly increased in the sera of visceral leishmaniasis patients, and the IFNL genetic variant rs12979860 was significantly associated with susceptibility to leishmaniasis.
Distinct structural motifs are necessary for targeting and import of Tim17 in
Trypanosoma brucei
mitochondrion
Authors: Darden Chauncey , Donkor Joseph E. , Korolkova Olga , Barozai Muhammad Younas Khan , Chaudhuri Minu 
Published: January 2024

ABSTRACT

Nuclear-encoded mitochondrial proteins are correctly translocated to their proper sub-mitochondrial destination using location-specific mitochondrial targeting signals and via multi-protein import machineries (translocases) in the outer and inner mitochondrial membranes (TOM and TIMs, respectively). However, targeting signals of multi-pass Tims are less defined. Here, we report the characterization of the targeting signals of
Trypanosoma brucei
Tim17 (TbTim17), an essential component of the most divergent TIM complex. TbTim17 possesses a characteristic secondary structure including four predicted transmembrane (TM) domains in the center with hydrophilic N- and C-termini. After examining mitochondrial localization of various deletion and site-directed mutants of TbTim17 in
T. brucei
using subcellular fractionation and confocal microscopy, we located at least two internal targeting signals (ITS): (i) within TM1 (31–50 AAs) and (ii) TM4 + loop 3 (120–136 AAs). Both signals are required for proper targeting and integration of TbTim17 in the membrane. Furthermore, a positively charged residue (K
122
) is critical for mitochondrial localization of TbTim17. This is the first report of characterizing the ITS for a multipass inner membrane protein in a divergent eukaryote, like
T. brucei
.

IMPORTANCE

African trypanosomiasis (AT) is a deadly disease in human and domestic animals, caused by the parasitic protozoan
Trypanosoma brucei
. Therefore, AT is not only a concern for human health but also for economic development in the vast area of sub-Saharan Africa.
T. brucei
possesses a single mitochondrion per cell that imports hundreds of nuclear-encoded mitochondrial proteins for its functions.
T. brucei
Tim17 (TbTim17), an essential component of the TbTIM17 complex, is a nuclear-encoded protein; thus, it is necessary to be imported from the cytosol to form the TbTIM17 complex. Here, we demonstrated that the internal targeting signals within the transmembrane 1 (TM1) and TM4 with loop 3, and residue K122 are required collectively for import and integration of TbTim17 in the
T. brucei
mitochondrion. This information could be utilized to block TbTim17 function and parasite growth.
High-precision U-Pb geochronology links magmatism in the Southwestern Laurentia large igneous province and Midcontinent Rift
Authors: Mohr M.T. , Schmitz M.D. , Swanson-Hysell N.L. , Karlstrom K.E. , Macdonald F.A. , Holland M.E. , Zhang Y. , Anderson N.S. 
Published: January 2024

Abstract
The Southwestern Laurentia large igneous province (SWLLIP) comprises voluminous, widespread ca 1.1 Ga magmatism in the southwestern United States and northern Mexico. The timing and tempo of SWLLIP magmatism and its relationship to other late Mesoproterozoic igneous provinces have been unclear due to difficulties in dating mafic rocks at high precision. New precise U-Pb zircon dates for comagmatic felsic segregations within mafic rocks reveal distinct magmatic episodes at ca. 1098 Ma (represented by massive sills in Death Valley, California, the Grand Canyon, and central Arizona) and ca. 1083 Ma (represented by the Cardenas Basalts in the Grand Canyon and a sill in the Dead Mountains, California). The ca. 1098 Ma magmatic pulse was short-lived, lasting 0.25−0.24+0.67 m.y., and voluminous and widespread, evidenced by the ≥100 m sills in Death Valley, the Grand Canyon, and central Arizona, consistent with decompression melting of an upwelling mantle plume. The ca. 1083 Ma magmatism may have been generated by a secondary plume pulse or post-plume lithosphere extension.
The ca. 1098 Ma pulse of magmatism in southwestern Laurentia occurred ~2 m.y. prior to an anomalous renewal of voluminous melt generation in the Midcontinent Rift of central Laurentia that is recorded by the ca. 1096 Ma Duluth Complex layered mafic intrusions. Rates of lateral plume spread predicted by mantle plume lubrication theory support a model where a plume derived from the deep mantle impinged near southwestern Laurentia, then spread to thinned Midcontinent Rift lithosphere over ~2 m.y. to elevate mantle temperatures and generate melt. This geodynamic hypothesis reconciles the close temporal relationships between voluminous magmatism across Laurentia and provides an explanation for that anomalous renewal of high magmatic flux within the protracted magmatic history of the Midcontinent Rift.
Semi-pelagic self-adjusting otter boards: effects on the catching performance of a demersal trawl
Authors: Eighani Morteza , Malta Tiago Veiga , Melli Valentina , O'Neill Finbarr G. 
Published: January 2024

In this study, we investigate whether replacing conventional seabed-contacting otter boards with semi-pelagic self-adjusting otter (SAO) boards, which have the ability to maintain a given height above the seabed, affects the catch efficiency of a demersal fish trawl. Experimental fishing trials, using the alternate haul method, were conducted in the Kattegat and Skagerrak with three otter board configurations using conventional seabed-contacting otter boards; the SAO set to maintain a target height over the seabed of 1 m; and the SAO set to maintain a target height of 5 m. Replacing conventional otter boards with SAO resulted in a loss of catch efficiency for haddock ( Melanogrammus aeglefinus), whiting ( Merlangius merlangus), and plaice ( Hippoglossoides platessoides), while no significant difference was found for cod ( Gadus morhua), common dab ( Limanda limanda), and lemon sole ( Microstomus kitt). When comparing the SAO-1 m and SAO-5 m, it was observed that SAO-5 m resulted in a loss of catch efficiency for haddock and plaice, a minimal reduction for cod, and no significant difference for whiting, common dab, and lemon sole.
Inflationary quantum spectrum of the quasi-isotropic Universe
Authors: Bortolotti Nicola , Montani Giovanni 
Published: January 2024

AbstractWe investigate the quantum dynamics of the quasi-isotropic inflationary solution. This is achieved by deriving the Lagrangian and Hamiltonian for both the FLRW background and the inhomogeneous correction, via an expansion of the Einstein–Hilbert action up to second order in the perturbation amplitudes. Then we implement a semiclassical WKB scenario for which the inhomogeneous component of the Universe is treated as a “small” quantum subsystem, evolving on the classical isotropic background. Starting from the Wheeler–DeWitt equation, we recover a Schrödinger dynamics for the perturbations, in which the time dependence of the wave function emerges thanks to the classicality of the background, and we solve it for an inflationary phase. The main result of this paper is to show that, while the scalar component of the power spectrum has the standard scale invariant profile, the tensor one results to be not constrained by the inflationary expansion, apart from an overall normalization factor which guarantees a small tensor-to-scalar ratio. This means that the spatial distribution of the quasi-isotropic correction to the metric remains preserved, with the consequence that some information about the pre-inflationary Universe survives to the de Sitter expansion.
Abstract A001: Discovery of imidazo [4,5-c]pyridin-2-ones as selective inhibitors of DNA-dependent protein kinase and effective radiosensitizers
Authors: Hay Michael P. , Hong Cho R. , Liew Lydia P. , Dickson Benjamin D. , Wong Way W. , O'Brien-Gortner Sophia F. , Airey Rebecca , Jaiswal Jagdish , Wilson William R. , Jamieson Stephen M. 
Published: January 2024

Abstract
Inhibition of the repair of radiation-induced DNA double strand breaks (DSB) offers the potential to sensitize tumors to radiation therapy. The dominant role of non-homologous end-joining in the repair of radiation-induced DSBs indicates that DNA-dependent protein kinase (DNA-PK) is an excellent target for the development of radiosensitizers. We report the discovery of a new chemical class of kinase inhibitor based on the imidazo[4,5-c]pyridin-2-one scaffold. The class was developed by scaffold-hopping from the pan phosphoinositide 3-kinsase (PI3K) and PI3K-like kinase (PIKK) inhibitor dactolisib. Iterative development culminated in the identification of SN39536 as a low nM DNA-PK inhibitor with excellent selectivity. Further modification led to the discovery of the more potent and more selective SN40905. Both SN39536 and SN40905 were effective inhibitors of DNA-PK kinase activity in a biochemical assay with substantial selectivity for DNA-PK across the PIKK and PI3K families. Both compounds selectively inhibited growth of HAP1 PRKDC wild-type cells when combined with radiation, but not the corresponding PRKDC-/- cells. SN39536 and SN40905 were effective radiosensitizers of colorectal carcinoma (HCT116), non-small cell lung cancer (H460, H1299, and A549), pancreatic (BxPC-3, PANC-1, and MiaPaCa-2) and head and neck squamous cell carcinoma (FaDu and UT-SCC-74B) cells determined using a clonogenic survival endpoint. Both SN39536 and SN40905 displayed high oral bioavailability. When administered PO at a range of non-toxic doses, both SN39536 and SN40905 provided significant additional tumor cell killing of HCT116, UT-SCC-74B, and BxPC-3 tumor xenografts in combination with a single (13 Gy) radiation treatment determined by ex vivo clonogenic survival assays. SN39536 also provided substantial tumor growth inhibition of HCT116 tumor xenografts in combination with RAD (10 Gy). SN39536 and SN40905 represent a new, potent, and selective class of DNA-PK inhibitors with significant potential as radiosensitizers for the treatment of human cancers.
Citation Format: Michael P. Hay, Cho R. Hong, Lydia P. Liew, Benjamin D. Dickson, Way W. Wong, Sophia F. O'Brien-Gortner, Rebecca Airey, Jagdish Jaiswal, William R. Wilson, Stephen M. Jamieson. Discovery of imidazo [4,5-c]pyridin-2-ones as selective inhibitors of DNA-dependent protein kinase and effective radiosensitizers [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr A001.
Abstract A025: FANCI regulates Fanconi anemia pathway and counteracts the effects of DNA damaging chemotherapy in prostate cancer
Authors: Kaljunen Heidi , Taavitsainen Sinja , Kaarijärvi Roosa , Takala Eerika , Paakinaho Ville , Nykter Matti , Bova G. Steven , Ketola Kirsi 
Published: January 2024

Abstract
Prostate cancer is one of the leading causes of death among men worldwide and thus research on the genetic factors enabling the formation of treatment resistant cancer cells is crucial for improving patient outcomes. Here, we report a cell-line specific dependence on FANCI and related signaling pathways to counteract effects of DNA damaging chemotherapy in prostate cancer. Our results reveal that FANCI depletion results in significant downregulation of Fanconi anemia (FA) pathway members in prostate cancer cells indicating that FANCI is an important regulator of FA pathway. Furthermore, we found that FANCI silencing reduces proliferation in p53-expressing prostate cancer cells. This extends the evidence that inactivation of FANCI may convert cancer cells from a resistant to an eradicable state under the stress of DNA-damaging chemotherapy. Our results also indicate that high expression of FA pathway genes correlates with poorer survival in prostate cancer patients. Moreover, genomic alterations of FA pathway members are prevalent in prostate adenocarcinoma patients; mutation and copy number information for the FA pathway genes in seven patient cohorts (N = 1732 total tumor samples) reveals that 1025 (59.2%) tumor samples have an alteration in at least one of the FA pathway genes, suggesting that genomic alteration of the pathway is a prominent feature in patients with the disease.
Citation Format: Heidi Kaljunen, Sinja Taavitsainen, Roosa Kaarijärvi, Eerika Takala, Ville Paakinaho, Matti Nykter, G. Steven Bova, Kirsi Ketola. FANCI regulates Fanconi anemia pathway and counteracts the effects of DNA damaging chemotherapy in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr A025.
Abstract B011: CDK9-55 guides the anaphase-promoting complex/cyclosome (APC/C) in choosing the DNA repair pathway by affecting the UFL1 ubiquitination
Authors: Alfano Luigi 
Published: January 2024

Abstract
DNA double-strand breaks (DSBs) contribute to genome instability, a key feature of cancer. DSBs are mainly repaired by homologous recombination (HR) and non-homologous end-joining (NHEJ). We investigated the role of an isoform of the multifunctional cyclin-dependent kinase 9, CDK9-55, in DNA repair, by generating CDK9-55-knockout HeLa clones (through CRISPR-Cas9), which showed potential HR dysfunction. A phosphoproteomic screening in these clones treated with camptothecin (CPT) revealed that CDC23 (cell division cycle 23), a component of the E3-ubiquitin ligase APC/C (anaphase-promoting complex/cyclosome), is a new substrate of CDK9-55, with S588 being its putative phosphorylation site. Mutated non-phosphorylatable CDC23(S588A) affected the repair pathway choice by impairing HR and favoring error prone NHEJ. Moreover, CDC23(S588A) promoted the ubiquitination of UFL1, a recently identified HR player. Overall, CDK9-55 could guide APC/C in choosing the correct DNA repair pathway, possibly by regulating UFL1 stability. This CDK9 role should be considered when designing CDK-inhibitor-based cancer therapies.
Citation Format: Luigi Alfano. CDK9-55 guides the anaphase-promoting complex/cyclosome (APC/C) in choosing the DNA repair pathway by affecting the UFL1 ubiquitination [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr B011.