bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trust and transfer during the covid-19 pandemic: did digital cash transfer save lives?
Authors: Tampubolon Gindo 
Published: April 2024

ABSTRACTBACKGROUNDIn the first semester of 2020 one in six people in the world (1.36 billion) received cash transfers to tide them over the spreading pandemic that originated in Wuhan. By December 2021 it had claimed up to 18.2 million excess deaths. Compared to no (digital) transfer, did digital cash transfer reduce excess deaths? Serendipitously, two years earlier the world reported levels of trust in science. Did such trust inoculate societies from the pandemic?MATERIALS & METHODSThe growing excess deaths literature distinguishes causal factors (e.g. digital transfer) from risk factors (e.g. trust). During the pandemic period, no randomised trials of digital transfer with excess deaths as primary outcome were registered. This study used reports from 170 countries and applied endogenous treatment models to overcome the endogeneity of digital transfer.RESULTS & DISCUSSIONI found that serendipity matters: countries with high trust in science suffered fewer excess deaths. But creativity matters more. Digital transfers –some creatively scrambled from scratch– reduced excess deaths by many more. Equally marked, North-South inequity in excess deaths persists, consistent with the concentration of vaccine distributions in the North early on. All three are statistically significant.A series of robustness analyses points to the results being reliable to change in outcome estimates, change in trust sources, and change in treatment of omitted countries. Mechanistic analyses show evidence that digital transfer created leg room for governments to expand stringent restrictions to control the spread of SARS-CoV-2, while in the South it weakened the correlation between informal economy and excess deaths. This study of the causal effect of digital cash transfer on a hard outcome (excess deaths) revealed ample global digital dividends across the largest number of countries. This new evidence also suggests that improving and monitoring trust in science can offer considerable benefits for humanity.
Genetic Risk, Health-Associated Lifestyle, and Risk of Early-onset Total Cancer and Breast Cancer
Authors: Zhang Yin , Lindström Sara , Kraft Peter , Liu Yuxi 
Published: April 2024

AbstractImportanceEarly-onset cancer (diagnosed under 50 years of age) is associated with aggressive disease characteristics and its rising incidence is a global concern. The association between healthy lifestyle and early-onset cancer and whether it varies by common genetic variants is unknown.ObjectiveTo examine the associations between genetic risk, lifestyle, and risk of early-onset cancers.Design, Setting, and ParticipantsWe analyzed a prospective cohort of 66,308 white British participants who were under age 50 and free of cancer at baseline in the UK Biobank.ExposuresSex-specific composite total cancer polygenic risk scores (PRSs), a breast cancer-specific PRS, and sex-specific health-associated lifestyle scores (HLSs, which summarize smoking status, body mass index [males only], physical activity, alcohol consumption, and diet).Main Outcomes and MeasuresHazard ratios (HRs) and 95% confidence intervals (CIs) for early-onset total and breast cancer.ResultsA total of 1,247 incident invasive early-onset cancer cases (female: 820, male: 427, breast: 386) were documented. In multivariable-adjusted analyses with 2-year latency, higher genetic risk (highest vs. lowest tertile of PRS) was associated with significantly increased risks of early-onset total cancer in females (HR, 95% CI: 1.85, 1.50-2.29) and males (1.94, 1.45-2.59) as well as early-onset breast cancer in females (3.06, 2.20-4.25). An unfavorable lifestyle (highest vs. lowest category of HLS) was associated with higher risk of total cancer and breast cancer in females across genetic risk categories; the association with total cancer was stronger in the highest genetic risk category than the lowest: HRs in females and men were 1.85 (1.02, 3.36), 3.27 (0.78, 13.72) in the highest genetic risk category and 1.15 (0.44, 2.98), 1.16 (0.39, 3.40) in the lowest.Conclusions and RelevanceBoth genetic and lifestyle factors were independently associated with early-onset total and breast cancer risk. Compared to those with low genetic risk, individuals with a high genetic risk may benefit more from adopting a healthy lifestyle in preventing early-onset cancer.
Identification of novel candidate genes associated with the symbiotic compatibility of soybean with rhizobia under natural conditions
Authors: Teraishi Masayoshi , Sakaguchi Kosuke , Tsuchimoto Takahiro , Yoshikawa Takanori 
Published: April 2024

AbstractA robust symbiotic relationship between soybean and rhizobia can enhance the yield and quality of soybeans by reducing nitrogen fertilizer inputs, thereby contributing to sustainable agriculture. The genetic interplay between soybean cultivars and the rhizobial species colonizing their roots under natural conditions remains underexplored. This study builds on the observation that the prevalence of rhizobial species associated with the soybean cultivars ‘Peking’ and ‘Tamahomare’ varies significantly. Herein, we performed a quantitative trait loci (QTL) analysis of the proportion ofRhizobiumspecies present in the root nodules of these cultivars using recombinant inbred lines derived from a cross between ‘Peking’ and ‘Tamahomare.’ A major QTL was identified on chromosome 18, accounting for 42% of the phenotypic variation, and was subsequently localized to a 240 kb region. The RNA-seq analysis indicated that a single gene featuring nucleotide binding site–leucine-rich repeat domains exhibited markedly different expression levels in parent cultivars within the QTL region. As this locus is distinct from the chromosomal regions containing known nodule-related genes, such asRjorrj, it likely represents a novel gene involved in symbiosis between rhizobia and soybeans. Further research of the function and role of this new gene has potential to improve soybean yield and contribute to sustainable agriculture under low nitrogen fertilizer conditions.
Sepal shape variability is robust to cell size heterogeneity in Arabidopsis
Authors: Trinh Duy-Chi , Lionnet Claire , Trehin Christophe , Hamant Olivier 
Published: April 2024

AbstractHow organisms produce organs with robust shapes and sizes is still an open question. In recent years, the Arabidopsis sepal has been used as a model system to study this question because of its highly reproducible shape and size. One interesting aspect of the sepal is that its epidermis contains cells with very different sizes. Previous reports had qualitatively shown that sepals with more or less giant cells exhibit comparable final size and shape. Here we investigate this question using quantitative approaches. We find that a mixed population of cell size modestly contribute to the normal width of the sepal, but is not essential for its shape robustness. Furthermore, in a mutant with increased cell and organ growth variability, the change in final sepal shape caused by giant cells is exaggerated, but the shape robustness is not affected. This formally demonstrates that sepal shape variability is robust to cell size heterogeneity.Main conclusionA mixed population of cells with varied sizes plays a limited role in ensuring the symmetrical shape of the sepal, and is not essential for sepal shape robustness in Arabidopsis.
Impairment of proteasome-associated deubiquitinating enzyme Uchl5/UBH-4 affects autophagy
Authors: Jha Sweta , Pispa Johanna , Holmberg Carina I. 
Published: April 2024

AbstractThe autophagy-lysosomal pathway (ALP) and the ubiquitin-proteasome system (UPS) are the two major intracellular proteolytic systems that mediate protein turnover in eukaryotes. Although a crosstalk exists between these two systems, it is still unclear how UPS and ALP interactin vivo. Here, we have investigated how impaired function of the proteasome-associated deubiquitinating enzyme (DUB) Uchl5/UBH-4, a regulator of proteasome activity, affects autophagy in human cells and in various tissues in a multicellular organism. We have used the established GFP-LC3-RFP-LC3ΔG autophagy reporter HeLa cell line and show that downregulation ofUchl5by siRNA reduces autophagy, which is similar to a previously reported role of the proteasome-associated DUB Usp14 on autophagy. ExposingCaenorhabditis eleganscarrying the autophagy reporter mCherry::GFP::LGG-1 toubh-4orusp-14RNAi, or to their pharmacological inhibitors, results in diverse effects regarding the numbers of autophagosomes and autolysosomes in the intestine, hypodermal seam cells and the pharynx. Our results reveal that the proteasome-associated DUBs Uchl5/UBH-4 and Usp14 affect autophagy in a differential tissue manner. A deeper insight into the interplay between UPS and ALP in various tissuesin vivohas the potential to promote development of therapeutic approaches for disorders associated with proteostasis dysfunction.SummaryModulation of UPS via pharmacological or genetic impairment of the proteasome-associated DUB Uchl5/UBH-4 affects autophagy in human cells and in a tissue-differential manner inC. elegans.
Super-resolution going viral: T4 virus particles as perfect nature-designed 3D-Bio-NanoRulers
Authors: Gallea José Ignacio , Nevskyi Oleksii , Kaźmierczak Zuzanna , Chen Tao , Miernikiewicz Paulina , Chizhik Anna , Dąbrowska Krystyna , Bates Mark , Enderlein Jörg 
Published: April 2024

In the burgeoning field of super-resolution fluorescence microscopy, significant efforts are being dedicated to expanding its applications into the three-dimensional domain. Various methodologies have been developed that enable isotropic resolution at the nanometer scale, facilitating the visualization of three-dimensional subcellular structures with unprecedented clarity. Central to this progress is the need for reliable 3D structures that are biologically compatible for validating resolution capabilities. Choosing the optimal standard poses a considerable challenge, necessitating, among other attributes, precisely defined geometry and the capability for specific labeling at sub-diffraction-limit distances.In this context, we introduce the use of the non-human-infecting virus, bacteriophage T4, as an effective and straightforward bio-ruler for three-dimensional super-resolution imaging. Employing DNA point accumulation for imaging in nanoscale topography (DNA-PAINT) along with the technique of astigmatic imaging, we uncover the icosahedral capsid of the bacteriophage T4, measuring 120 nm in length and 86 nm in width, and its hollow viral tail. This level of detail in light microscopy represents a significant advancement. We further outline a simple protocol for the production and preparation of samples. Moreover, we explore the extensive potential of bacteriophage T4 as a multi-faceted 3D bio-ruler, proposing its application as a novel benchmark for three-dimensional super-resolution imaging in biological studies.
Deoxyuridine-rich cytoplasmic DNA antagonizes STING-dependent innate immune responses and sensitizes resistant tumors to anti-PD-L1 therapy
Authors: Pandya Pinakin , Vendetti Frank P. , El-Ghoubaira Joseph , Pathak Sudipta , Deppas Joshua J. , Jones Reyna , Columbus Anthony V. , Zhang Yunqi , Ivanov Daniel , Huang Ziyu , MacDonald Kate M. , Harding Shane M. , Buj Raquel , Aird Katherine M. , Beumer Jan H. , Sobol Robert W. , Bakkenist Christopher J. 
Published: April 2024

ABSTRACTDNA damage and cytoplasmic DNA induce type-1 interferon (IFN-1) and potentiate responses to immune checkpoint inhibitors. Our prior work found that inhibitors of the DNA damage response kinase ATR (ATRi) induce IFN-1 and deoxyuridine (dU) incorporation by DNA polymerases, akin to antimetabolites. Whether and how dU incorporation is required for ATRi-induced IFN-1 signaling is not known. Here, we show that ATRi-dependent IFN-1 responses require uracil DNA glycosylase (UNG)-initiated base excision repair and STING. Quantitative analyses of nine distinct nucleosides reveals that ATRi induce dU incorporation more rapidly in UNG wild-type than knockout cells, and that induction of IFN-1 is associated with futile cycles of repair. While ATRi induce similar numbers of micronuclei in UNG wild-type and knockout cells, dU containing micronuclei and cytoplasmic DNA are increased in knockout cells. Surprisingly, DNA fragments containing dU block STING-dependent induction of IFN-1, MHC-1, and PD-L1. Furthermore, UNG knockout sensitizes cells to IFN-γin vitro, and potentiates responses to anti-PD-L1 in resistant tumorsin vivo. These data demonstrate an unexpected and specific role for dU-rich DNA in suppressing STING-dependent IFN-1 responses, and show that UNG-deficient tumors have a heightened response to immune checkpoint inhibitors.STATEMENT OF SIGNIFICANCEAntimetabolites disrupt nucleotide pools and increase dU incorporation by DNA polymerases. We show that unrepaired dU potentiates responses to checkpoint inhibitors in mouse models of cancer. Patients with low tumor UNG may respond to antimetabolites combined with checkpoint inhibitors, and patients with high tumor UNG may respond to UNG inhibitors combined with checkpoint inhibitors.
Re-appraising the role of T-cell derived interferon gamma in restriction ofMycobacterium tuberculosisin the murine lung
Authors: Maciag Karolina , Plumlee Courtney , Cohen Sara , Gern Benjamin , Urdahl Kevin 
Published: April 2024

ABSTRACTT cells producing interferon gamma (IFNγ) have long been considered a stalwart for immune protection againstMycobacterium tuberculosis(Mtb), but their relative importance to pulmonary immunity has been challenged by murine studies which achieved protection by adoptively transferredMtb-specific IFNγ-/-T cells. Using IFNγ-/-T cell chimeric mice and adoptive transfer of IFNγ-/-T cells into TCRβ-/-δ-/-mice, we demonstrate that control of lungMtbburden is in fact dependent on T cell-derived IFNγ, and furthermore, mice selectively deficient in T cell-derived IFNγ develop exacerbated disease compared to T cell-deficient controls despite equivalent lung bacterial burdens. Deficiency in T cell-derived IFNγ skews infected and bystander monocyte-derived macrophages (MDMs) to an alternative M2 phenotype, and promotes neutrophil and eosinophil influx. Our studies support an important role for T cell-derived IFNγ in pulmonary immunity against TB.
High temperature treatment optimized for symbiont suppression in an obligatory gut bacterial symbiosis in the stinkbugPlautia stali
Authors: Cai Wen-Jin , Moriyama Minoru , Fukatsu Takema 
Published: April 2024

AbstractIn the era of global warming, much attention has been paid to the possibility that high temperature may influence diverse insects not only directly but also indirectly via effects on their symbiotic microorganisms. The stinkbugPlautia stalidevelops a midgut symbiotic organ that harbors a specific bacterial symbiont indispensable for its growth and survival. Being maintainable in laboratory and tractable experimentally,P. staliis recently highlighted as a model system to investigate the mechanisms underpinning insect-microbe symbiotic interactions. In this study, we reared newly-emerged adult insects ofP. staliunder different temperature conditions for 8 days and monitored how their symbiotic organs and symbiotic bacteria are affected. While all insects survived at temperatures from 25°C to 37°C, some insects died at 38°C, 39°C and 40°C, wherein mortality rates increased as temperature elevated. While the symbiotic organs of the normal insects exhibited vivid yellow color, the symbiotic organs of the insects reared at 35°C or higher frequently exhibited abnormal colors such as pale yellow, yellowish white, or white, the extent of which became more severe as temperature elevated. Symbiont quantification revealed that, while the symbiont titers were almost constant for 8 days at 25°C and 30°C, the symbiont titers on the 8thday drastically declined to 1/100 at 35℃ and 1/10000 at 37°C and 39°C. Based on these results, we propose that rearing at 37°C for a week is a recommended treatment regime by which the symbiont is effectively suppressed with minimal damage to the host insect.
Intracranial aneurysm stiffness assessment using 4D flow MRI
Authors: Koizumi Satoshi , Kin Taichi , Sekine Tetsuro , Kiyofuji Satoshi , Umekawa Motoyuki , Saito Nobuhito 
Published: April 2024

AbstractBackgroundAlthough arterial stiffness is a known biomarker for cardiovascular events and stroke, there is limited information in the literature regarding the stiffness of intracranial aneurysms. This study aimed to assess intracranial aneurysm stiffness using four-dimensional flow magnetic resonance imaging (4D flow MRI).MethodsA total of 27 aneurysms in 25 patients with internal carotid artery aneurysms were included. Using 4D flow MRI, we measured the arterial pulse waveform during a cardiac cycle at planes proximal and distal to the target aneurysm. The damping of these waveforms through the aneurysm was defined as the aneurysm damping index (ADI) and compared with that of the contralateral side. Additionally, we investigated the clinical factors associated with the ADI.ResultsADI assessment was successful in all cases. The obtained ADI was 1.18 ± 0.28 (mean ± standard deviation), significantly larger than 1.0 (P=0.0027 [t-test]). The ADI on the aneurysm side was larger than on the contralateral side (1.19 ± 0.30 vs 1.05 ± 0.17, P=0.029 [t-test]). On multivariate analysis, the use of beta-blockers (β=0.46, P=0.015) and smoking history (β=-0.22, P=0.024) showed a significant correlation with ADI.ConclusionsWe proposed a novel method to assess the stiffness of intracranial aneurysms using 4D flow MRI. The quantitative observation of the damping of arterial pulse waves revealed a correlation between ADI and clinical factors, such as the use of antihypertensive drugs and smoking. Further studies should focus on evaluating the aneurysm stiffness and its clinical applications.
Biallelic Variants inCCN2Underlie an Autosomal Recessive Kyphomelic Dysplasia
Authors: Singh Swati , Danda Sumita , Sharma Neetu , Shah Hitesh , Madhuri Vrisha , Altaf Mir Tariq , Padala Nadia Zipporah , Medishetti Raghavender , Ekbote Alka , Bhavani Gandham SriLakshmi , Sevilimedu Aarti , Girisha Katta M 
Published: April 2024

AbstractKyphomelic dysplasia is a rare heterogenous group of skeletal dysplasia, characterized by bowing of the limbs, severely affecting femora with distinct facial features. Despite its first description nearly four decades, the precise molecular basis of this condition remained elusive until the recent discovery ofde novovariants in the KIF5B-related kyphomelic dysplasia. We ascertained two unrelated consanguineous families with kyphomelic dysplasia. They had six affected offsprings and we performed a detailed clinical evaluation, skeletal survey, and exome sequencing in three probands. All the probands had short stature, cleft palate, and micro-retrognathia. Radiographs revealed kyphomelic femora, bowing of long bones, radial head dislocations and spondyloepimetaphyseal dysplasia. We noted two novel homozygous variants inCCN2as possible candidates that segregated with the phenotype in the families: a missense variant c.443G>A; p.(Cys148Tyr) in exon 3 and a frameshift variant, c.779_786del; p.(Pro260LeufsTer7) in exon 5.CCN2is crucial for proliferation and differentiation of chondrocytes. Earlier studies have shown thatCcn2-deficient mice exhibit twisted limbs, short and kinked sterna, broad vertebrae, domed cranial vault, shorter mandibles, cleft palate and impaired osteoclastogenesis. We studied the impact ofCCN2knockout in zebrafish models via CRISPR-Cas9 gene editing. F0 knockouts ofccn2ain zebrafish showed altered body curvature, impaired cartilage formation in craniofacial region and either bent or missing tails recapitulating the human phenotype. Our observations in humans and zebrafish combined with previously described skeletal phenotype ofCcn2knock out mice, confirm that biallelic loss of function variants inCCN2result in an autosomal recessive kyphomelic dysplasia.
Apraxic imitation deficits in Alzheimer’s disease are associated with altered dynamic connectivity
Authors: Kuzu Taylan D. , Jaeger Elena , Bonkhoff Anna K. , Wunderle Veronika , Bischof Gérard N. , Giehl Kathrin , Schmieschek Maximilian H. T. , Onur Özgür A. , Jessen Frank , Fink Gereon R. , Drzezga Alexander , Weiss Peter H. 
Published: April 2024

AbstractApraxia is a common symptom in individuals with Alzheimer’s disease (AD). However, the neural mechanisms underlying apraxic deficits in AD remain elusive. Therefore, the current study focuses on the association between altered functional connectivity and apraxia in individuals with AD examining the hypothesis that apraxic deficits in AD result from dysfunction in praxis-related networks.To this aim, we examined the association between changes in static and dynamic functional connectivity (FC) of resting-state networks and apraxia in AD. Resting-state functional MRI data was acquired in 13 patients with tau-and amyloid-positive AD, who underwent an extensive neuropsychological, motor and apraxia assessment, and 13 matched healthy control participants. The static and dynamic functional connectivity of resting state networks revealed by independent component analysis (ICA) were assessed and connectivity measures were correlated with apraxia scores.Across all participants, we identified two distinct dynamic FC states using a sliding window approach. Patients with AD exhibited prolonged dwell times in the first state characterized by weaker connectivity and spent overall more time in this state, i.e., showed an increased fraction time in the first state. Apraxic deficits, especially deficits in imitating gestures, correlated significantly with the fraction time of both states as well as with the dwell time of the weakly connected dynamic state.Data suggest that apraxic imitation deficits in AD are associated with dysfunction of praxis networks characterized by altered dynamic FC.