bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA polymerase redistribution supports growth in E. coli strains with a minimal number of rRNA operons
Authors: Fan Jun , El Sayyed Hafez , Pambos Oliver J , Stracy Mathew , Kyropoulos Jingwen , Kapanidis Achillefs N 
Published: June 2023

Abstract
Bacterial transcription by RNA polymerase (RNAP) is spatially organized. RNAPs transcribing highly expressed genes locate in the nucleoid periphery, and form clusters in rich medium, with several studies linking RNAP clustering and transcription of rRNA (rrn). However, the nature of RNAP clusters and their association with rrn transcription remains unclear. Here we address these questions by using single-molecule tracking to monitor the subcellular distribution of mobile and immobile RNAP in strains with a heavily reduced number of chromosomal rrn operons (Δrrn strains). Strikingly, we find that the fraction of chromosome-associated RNAP (which is mainly engaged in transcription) is robust to deleting five or six of the seven chromosomal rrn operons. Spatial analysis in Δrrn strains showed substantial RNAP redistribution during moderate growth, with clustering increasing at cell endcaps, where the remaining rrn operons reside. These results support a model where RNAPs in Δrrn strains relocate to copies of the remaining rrn operons. In rich medium, Δrrn strains redistribute RNAP to minimize growth defects due to rrn deletions, with very high RNAP densities on rrn genes leading to genomic instability. Our study links RNAP clusters and rrn transcription, and offers insight into how bacteria maintain growth in the presence of only 1–2 rrn operons.
Spatially resolved transcriptomic analysis of the germinating barley grain
Authors: Peirats-Llobet Marta , Yi Changyu , Liew Lim Chee , Berkowitz Oliver , Narsai Reena , Lewsey Mathew G , Whelan James 
Published: June 2023

AbstractSeeds are a vital source of calories for humans and a unique stage in the life cycle of flowering plants. During seed germination, the embryo undergoes major developmental transitions to become a seedling. Studying gene expression in individual seed cell types has been challenging due to the lack of spatial information or low throughput of existing methods. To overcome these limitations, a spatial transcriptomics workflow was developed for germinating barley grain. This approach enabled high-throughput analysis of spatial gene expression, revealing specific spatial expression patterns of various functional gene categories at a sub-tissue level. This study revealed over 14 000 genes differentially regulated during the first 24 h after imbibition. Individual genes, such as the aquaporin gene family, starch degradation, cell wall modification, transport processes, ribosomal proteins and transcription factors, were found to have specific spatial expression patterns over time. Using spatial autocorrelation algorithms, we identified auxin transport genes that had increasingly focused expression within subdomains of the embryo over time, suggesting their role in establishing the embryo axis. Overall, our study provides an unprecedented spatially resolved cellular map for barley germination and identifies specific functional genomics targets to better understand cellular restricted processes during germination. The data can be viewed at https://spatial.latrobe.edu.au/.
Enhanced mitochondrial G-quadruplex formation impedes replication fork progression leading to mtDNA loss in human cells
Authors: Doimo Mara , Chaudhari Namrata , Abrahamsson Sanna , L’Hôte Valentin , Nguyen Tran V H , Berner Andreas , Ndi Mama , Abrahamsson Alva , Das Rabindra Nath , Aasumets Koit , Goffart Steffi , Pohjoismäki Jaakko L O , López Marcela Dávila , Chorell Erik , Wanrooij Sjoerd 
Published: June 2023

Abstract
Mitochondrial DNA (mtDNA) replication stalling is considered an initial step in the formation of mtDNA deletions that associate with genetic inherited disorders and aging. However, the molecular details of how stalled replication forks lead to mtDNA deletions accumulation are still unclear. Mitochondrial DNA deletion breakpoints preferentially occur at sequence motifs predicted to form G-quadruplexes (G4s), four-stranded nucleic acid structures that can fold in guanine-rich regions. Whether mtDNA G4s form in vivo and their potential implication for mtDNA instability is still under debate. In here, we developed new tools to map G4s in the mtDNA of living cells. We engineered a G4-binding protein targeted to the mitochondrial matrix of a human cell line and established the mtG4-ChIP method, enabling the determination of mtDNA G4s under different cellular conditions. Our results are indicative of transient mtDNA G4 formation in human cells. We demonstrate that mtDNA-specific replication stalling increases formation of G4s, particularly in the major arc. Moreover, elevated levels of G4 block the progression of the mtDNA replication fork and cause mtDNA loss. We conclude that stalling of the mtDNA replisome enhances mtDNA G4 occurrence, and that G4s not resolved in a timely manner can have a negative impact on mtDNA integrity.
Metallohelices stabilize DNA three-way junctions and induce DNA damage in cancer cells
Authors: Malina Jaroslav , Kostrhunova Hana , Scott Peter , Brabec Viktor 
Published: June 2023

Abstract
DNA three-way junctions (3WJ) represent one of the simplest supramolecular DNA structures arising as intermediates in homologous recombination in the absence of replication. They are also formed transiently during DNA replication. Here we examine the ability of Fe(II)-based metallohelices to act as DNA 3WJ binders and induce DNA damage in cells. We investigated the interaction of eight pairs of enantiomerically pure Fe(II) metallohelices with four different DNA junctions using biophysical and molecular biology methods. The results show that the metallohelices stabilize all types of tested DNA junctions, with the highest selectivity for the Y-shaped 3WJ and minimal selectivity for the 4WJ. The potential of the best stabilizer of DNA junctions and, at the same time, the most selective 3WJ binder investigated in this work to induce DNA damage was determined in human colon cancer HCT116 cells. These metallohelices proved to be efficient in killing cancer cells and triggering DNA damage that could yield therapeutic benefits.
Dna2 removes toxic ssDNA-RPA filaments generated from meiotic recombination-associated DNA synthesis
Authors: Zhai Binyuan , Zhang Shuxian , Li Bo , Zhang Jiaming , Yang Xuan , Tan Yingjin , Wang Ying , Tan Taicong , Yang Xiao , Chen Beiyi , Tian Zhongyu , Cao Yanding , Huang Qilai , Gao Jinmin , Wang Shunxin , Zhang Liangran 
Published: June 2023

Abstract
During the repair of DNA double-strand breaks (DSBs), de novo synthesized DNA strands can displace the parental strand to generate single-strand DNAs (ssDNAs). Many programmed DSBs and thus many ssDNAs occur during meiosis. However, it is unclear how these ssDNAs are removed for the complete repair of meiotic DSBs. Here, we show that meiosis-specific depletion of Dna2 (dna2-md) results in an abundant accumulation of RPA and an expansion of RPA from DSBs to broader regions in Saccharomyces cerevisiae. As a result, DSB repair is defective and spores are inviable, although the levels of crossovers/non-crossovers seem to be unaffected. Furthermore, Dna2 induction at pachytene is highly effective in removing accumulated RPA and restoring spore viability. Moreover, the depletion of Pif1, an activator of polymerase δ required for meiotic recombination-associated DNA synthesis, and Pif1 inhibitor Mlh2 decreases and increases RPA accumulation in dna2-md, respectively. In addition, blocking DNA synthesis during meiotic recombination dramatically decreases RPA accumulation in dna2-md. Together, our findings show that meiotic DSB repair requires Dna2 to remove ssDNA-RPA filaments generated from meiotic recombination-associated DNA synthesis. Additionally, we showed that Dna2 also regulates DSB-independent RPA distribution.
Gene expressions associated with longer lifespan and aging exhibit similarity in mammals
Authors: Takasugi Masaki , Yoshida Yuya , Nonaka Yoshiki , Ohtani Naoko 
Published: June 2023

Abstract
Although molecular features underlying aging and species maximum lifespan (MLS) have been comprehensively studied by transcriptome analyses, the actual impact of transcriptome on aging and MLS remains elusive. Here, we found that transcriptional signatures that are associated with mammalian MLS exhibited significant similarity to those of aging. Moreover, transcriptional signatures of longer MLS and aging both exhibited significant similarity to that of longer-lived mouse strains, suggesting that gene expression patterns associated with species MLS contribute to extended lifespan even within a species and that aging-related gene expression changes overall represent adaptations that extend lifespan rather than deterioration. Finally, we found evidence of co-evolution of MLS and promoter sequences of MLS-associated genes, highlighting the evolutionary contribution of specific transcription factor binding motifs such as that of E2F1 in shaping MLS-associated gene expression signature. Our results highlight the importance of focusing on adaptive aspects of aging transcriptome and demonstrate that cross-species genomics can be a powerful approach for understanding adaptive aging transcriptome.
Mineral and bone metabolism markers and mortality in diabetic patients on haemodialysis
Authors: Martín-Carro Beatriz , Navarro-González Juan F , Ortiz Alberto , Zoccali Carmine , Floege Jürgen , Ferreira Manuel A , Gorriz-Teruel José L , Carrillo-López Natalia , Panizo Sara , Locatelli Francesco , Ketteler Markus , London Gerard M , Naves-Díaz Manuel , Alonso-Montes Cristina , Cannata-Andía Jorge B , Fernández-Martín José L 
Published: June 2023

ABSTRACT

Background
Diabetic patients on haemodialysis have a higher risk of mortality than non-diabetic patients. The aim of this COSMOS (Current management of secondary hyperparathyroidism: a multicentre observational study) analysis was to assess whether bone and mineral laboratory values [calcium, phosphorus and parathyroid hormone (PTH)] contribute to this risk.

Methods
COSMOS is a multicentre, open-cohort, 3-year prospective study, which includes 6797 patients from 227 randomly selected dialysis centres in 20 European countries. The association between mortality and calcium, phosphate or PTH was assessed using Cox proportional hazard regression models using both penalized splines smoothing and categorization according to KDIGO guidelines. The effect modification of the association between the relative risk of mortality and serum calcium, phosphate or PTH by diabetes was assessed.

Results
There was a statistically significant effect modification of the association between the relative risk of mortality and serum PTH by diabetes (P = .011). The slope of the curve of the association between increasing values of PTH and relative risk of mortality was steeper for diabetic compared with non-diabetic patients, mainly for high levels of PTH. In addition, high serum PTH (&gt;9 times the normal values) was significantly associated with a higher relative risk of mortality in diabetic patients but not in non-diabetic patients [1.53 (95% confidence interval 1.07–2.19) and 1.17 (95% confidence interval 0.91–1.52)]. No significant effect modification of the association between the relative risk of mortality and serum calcium or phosphate by diabetes was found (P = .2 and P = .059, respectively).

Conclusion
The results show a different association of PTH with the relative risk of mortality in diabetic and non-diabetic patients. These findings could have relevant implications for the diagnosis and treatment of chronic kidney disease–mineral and bone disorders.
Dynamics of urine proteomics biomarker and disease progression in patients with IgA nephropathy
Authors: Peters Björn , Beige Joachim , Siwy Justyna , Rudnicki Michael , Wendt Ralph , Ortiz Alberto , Sanz Ana Belen , Mischak Harald , Reich Heather N , Nasic Salmir , Mahmood Dana , Persson Anders , Fernström Anders , Weiner Maria , Stegmayr Bernd ,   the PersTIgAN Working Group, Beige Joachim , Wendt Ralph , Schmidt Ulrike , Siwy Justyna , Zürbig Petra , Mischak Harald , Durban Annika , Raad Julia , Golovko Igor , Reich Heather , Lam Ping , Yang Stuart , Sanz Ana Belen , Fernandez-Fernandez Beatriz , Rojas-Rivera Jorge Enrique , Perez-Gomez Maria Vanessa , Ortiz Alberto , Sanchez-Niño Maria Dolores , Sanchez-Rodriguez Jinny , Rudnicki Michael , Kerschbaum Julia , Leierer Johannes , Mayer Gert , Stegmayr Bernd , Peters Björn 
Published: June 2023

ABSTRACT

Background
Immunoglobulin A nephropathy (IgAN) frequently leads to kidney failure. The urinary proteomics-based classifier IgAN237 may predict disease progression at the time of kidney biopsy. We studied whether IgAN237 also predicts progression later in the course of IgAN.

Methods
Urine from patients with biopsy-proven IgAN was analyzed using capillary electrophoresis–mass spectrometry at baseline (IgAN237-1, n = 103) and at follow-up (IgAN237-2, n = 89). Patients were categorized as “non-progressors” (IgAN237 ≤0.38) and “progressors” (IgAN237 &gt;0.38). Estimated glomerular filtration rate (eGFR) and urinary albumin–creatinine ratio slopes were calculated.

Results
Median age at biopsy was 44 years, interval between biopsy and IgAN237-1 was 65 months and interval between IgAN237-1 and IgAN237-2 was 258 days (interquartile range 71–531). IgAN237-1 and IgAN237-2 values did not differ significantly and were correlated (rho = 0.44, P &lt; .001). Twenty-eight percent and 26% of patients were progressors based on IgAN237-1 and IgAN237-2, respectively. IgAN237 inversely correlated with chronic eGFR slopes (rho = –0.278, P = .02 for score-1; rho = –0.409, P = .002 for score-2) and with ±180 days eGFR slopes (rho = –0.31, P = .009 and rho = –0.439, P = .001, respectively). The ±180 days eGFR slopes were worse for progressors than for non-progressors (median –5.98 versus –1.22 mL/min/1.73 m2 per year for IgAN237-1, P &lt; .001; –3.02 vs 1.08 mL/min/1.73 m2 per year for IgAN237-2, P = .0047). In multiple regression analysis baseline progressor/non-progressor according to IgAN237 was an independent predictor of eGFR180days-slope (P = .001).

Conclusion
The urinary IgAN237 classifier represents a risk stratification tool in IgAN also later in the course of the dynamic disease. It may guide patient management in an individualized manner.
“I Get the Flavors and It Makes Me Love Vaping More”: How and Why Youth Users Modify Electronic Nicotine Delivery Systems
Authors: Churchill Victoria , Fairman Robert T , Brown Devon , Massey Zachary B , Ashley David L , Popova Lucy 
Published: June 2023

AbstractIntroductionYouth in the United States are using electronic nicotine delivery systems (ENDS) at a high rate. Modifications to ENDS by youth can introduce additional health hazards which have not been previously considered. To better understand these risks, we need more information on what these modifications are, the motivations behind them, and the sources of information on modifications.Aims and MethodsUtilizing a trained moderator, in 2020–2021, we conducted one-on-one interviews with 19 youth ENDS users aged 16–17 living in the United States and analyzed their responses using a qualitative description approach.ResultsThe most prominent modification was to the e-liquid; youth indicated they mixed e-juices to create new flavors and added substances not intended for vaping, including illicit drugs such as cannabis and cocaine. Few youths from our sample were interested in achieving a specific nicotine level to vape, and modifications to the battery, coil and wick were less frequently mentioned. Some of these modifications were motivated by a desire to achieve specific experiences with their device. At other times, modifications were made due to necessity because of limited access to ENDS devices and supplies. YouTube and peers were the main sources of information about modifying.ConclusionsYouth are making modifications that are both intended and unintended by the manufacturer. Adding illicit drugs and other substances not made for vaping is of particular concern. Understanding how youth modify ENDS and how that changes their use is important to guide regulatory policy intended to reduce harm to youth from ENDS use.ImplicationsYouth from our study indicated that they make modifications to the ENDS devices, specifically to the e-liquid. These modifications are both intended by the manufacturer, such as changing the e-liquid and replacing coils, and unintended, such as adding substances not meant for vaping. Future policies aimed at reducing youth ENDS use should consider mandating better safeguards against modifications that appeal to youth.
An experimental test of cause-related marketing and charitable giving
Authors: Murphy James J , Conlin Molly , Haugstad Bryan 
Published: June 2023

Abstract
We conducted a natural field experiment at a local toy store in Anchorage, Alaska to estimate the effect on consumer behavior when the firm’s charitable donation is conditional on the total dollar amount of the individual transaction. Results suggest that the donation offer resulted in a modest increase in both the share of transactions exceeding the minimum amount needed to qualify for the donation and sales revenue.
A Thousand Cuts
Authors: Kentikelenis Alexandros , Stubbs Thomas 
Published: June 2023

Abstract
The dominant policy response to economic crises over the past four decades has been the introduction of austerity. How has this mix of budget cuts and reforms to downsize the role of the state evolved over time? What affect has it had on social policies and on people’s lives? This book examines the activities of the world’s leading advocate of austerity: the International Monetary Fund (IMF). This international organization lends to countries facing economic trouble in exchange for the implementation of far-reaching austerity measures. Drawing on new data, the authors reveal that although the precise content of IMF-mandated austerity has changed considerably over time, the organization continues to place a high burden of reform on countries in crisis. These reforms then decrease the availability of important social services, and contribute to rises in income inequality and declines in population health. These findings form the first systematic assessment of how austerity has impacted people’s lives and livelihoods around the world. Will such policy mistakes be avoided in the postpandemic world? The early evidence presented in this book do not raise grounds for optimism. Public expenditure projections reveal that in 2023, 86 out of 189 countries—mostly middle-income ones—face contractions in government spending compared to their 2010s average, thereby exposing a cumulative total of 2.3 billion people to the socioeconomic consequences of budget cuts.
Introduction
Authors: Kentikelenis Alexandros , Stubbs Thomas 
Published: June 2023

Abstract
Austerity measures have been implemented far and wide across the globe in recent decades, commonly as a precondition to access financial assistance from the International Monetary Fund (IMF)—one of the world’s most powerful international organizations. This book seeks to provide a comprehensive account of the scope and diversity of IMF-mandated austerity measures over the past forty years, and to examine how austerity has impacted social policies and outcomes. This introductory chapter covers definitional issues on austerity, describes the roles of the IMF, explains what conditionality is and how it is applied in IMF loans, and outlines how the analysis will unfold throughout the volume.
The IMF and the COVID-19 Response
Authors: Kentikelenis Alexandros , Stubbs Thomas 
Published: June 2023

Abstract
In the aftermath of the COVID-19 pandemic the narrative emerging out of the International Monetary Fund (IMF) stresses avoiding a divergent recovery, whereby some countries steam ahead with high growth rates while others fall behind. In this account, the postcrisis period should not witness budget cuts, but investment in employment and human capital formation. Is austerity a thing of the past? This chapter reviews available evidence, focusing on public spending projections by the IMF and the precise content of IMF lending arrangements. Overall, the chapter shows that the abandonment of austerity argument is partially true now, but questionable in the medium term. An original analysis of public expenditure projections reveals that by 2023, 86 out of 189 countries—mostly middle-income ones—will face contractions in government spending compared to their 2010s average, thereby exposing a cumulative total of 2.3 billion people to the socioeconomic consequences of budget cuts.
The Future of IMF Lending
Authors: Kentikelenis Alexandros , Stubbs Thomas 
Published: June 2023

Abstract
How can the International Monetary Fund (IMF) be reformed so that its lending programs do not have the adverse socioeconomic consequences documented in this volume? This concluding chapter elaborates on what can be done for the IMF to effectively live up to its promise and potential. The chapter first examines how IMF programs impact meeting the goal of universal social protection, a requisite for achieving many of the Sustainable Development Goals. Subsequently, it draws attention to a newer area of IMF engagement: supporting countries in their climate change adaptation and mitigation efforts. As environmental degradation poses an existential challenge to humanity, ensuring that countries have appropriate macroeconomic frameworks in place to facilitate the green transition is of paramount importance, and the IMF has a role to play here too. Finally, the chapter spells out the challenges in the road ahead for the IMF, and what types of practices could underpin a reformed IMF.
Introduction
Authors: Key Aidan 
Published: June 2023

Abstract
The introduction establishes this book’s necessity in a rapidly changing world. This book dismantles some general assumptions about gender and show a path to greater gender inclusion in schools. The primary audience (educators) and secondary audience (parents) for the text are explained. This chapter underscores the crucial need to examine gender inclusion in schools from both systemic and personal perspectives. This chapter hints at the regressive nature of the present historical moment and points to divisive politics that muddy progress toward understanding and celebrating gender diversity. It also champions educators who have made tremendous efforts in embracing change.
Teaching Gender
Authors: Key Aidan 
Published: June 2023

Abstract
Chapter 3 presents a contextual framework for teaching gender in the K–12 classroom. This framework can be introduced in a simple, age-appropriate manner for younger students and modified as students mature and develop over time. The simplicity of this AEIOU (Anatomy, Expression, Identity, Orientation, Universal) framework provides parents and teachers with the clarity they need to meet students where they are, and it helps to avoid overcomplicating discussions of gender identity. The reader will gain greater confidence to engage in discussions with children of all ages about gender and how our gender is uniquely expressed in our daily lives.
Creating an Optimal School Environment
Authors: Key Aidan 
Published: June 2023

Abstract
Chapter 11 considers the following important stakeholders: the gender-diverse student, the rest of the student body, and the parent community. This chapter contains standalone content addressing the fundamentals of creating a student support plan, which is a collaboration between the student and the school. This chapter outlines approaches to student empowerment, such as fostering student leadership and the creation of student alliances. It also provides detailed approaches for parents who want to get more involved in their school community and suggests approaches for how educators can support parents in their involvement.