bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Mycobacterium tuberculosis Ku C-terminus is a multi-purpose arm for binding DNA and LigD and stimulating ligation
Authors: Sowa Dana J , Warner Monica M , Tetenych Andriana , Koechlin Lucas , Balari Pardis , Rascon Perez Jose Pablo , Caba Cody , Andres Sara N 
Published: October 2022

Abstract
Bacterial non-homologous end joining requires the ligase, LigD and Ku. Ku finds the break site, recruits LigD, and then assists LigD to seal the phosphodiester backbone. Bacterial Ku contains a core domain conserved with eukaryotes but has a unique C-terminus that can be divided into a minimal C-terminal region that is conserved and an extended C-terminal region that varies in sequence and length between species. Here, we examine the role of Mycobacterium tuberculosis Ku C-terminal variants, where we removed either the extended or entire C-terminus to investigate the effects on Ku–DNA binding, rates of Ku-stimulated ligation, and binding affinity of a direct Ku–LigD interaction. We find that the extended C-terminus limits DNA binding and identify key amino acids that contribute to this effect through alanine-scanning mutagenesis. The minimal C-terminus is sufficient to stimulate ligation of double-stranded DNA, but the Ku core domain also contributes to stimulating ligation. We further show that wildtype Ku and the Ku core domain alone directly bind both ligase and polymerase domains of LigD. Our results suggest that Ku-stimulated ligation involves direct interactions between the Ku core domain and the LigD ligase domain, in addition to the extended Ku C-terminus and the LigD polymerase domain.
Global mitigation efforts cannot neglect emerging emitters
Authors: Cui Can , Guan Dabo , Wang Daoping , Meng Jing , Chemutai Vicky , Brenton Paul , Zhang Shaohui , Shan Yuli , Zhang Qiang , Davis Steven J 
Published: October 2022

AbstractInternational efforts to avoid dangerous climate change have historically focused on reducing energy-related CO2 emissions from countries with either the largest economies (e.g. the EU and the USA) and/or the largest populations (e.g. China and India). However, in recent years, emissions have surged among a different and much less-examined group of countries, raising concerns that a next generation of high-emitting economies will obviate current mitigation targets. Here, we analyse the trends and drivers of emissions in each of the 59 countries where emissions in 2010–2018 grew faster than the global average (excluding China and India), project their emissions under a range of longer-term energy scenarios and estimate the costs of decarbonization pathways. Total emissions from these ‘emerging emitters’ reach as much as 7.5 GtCO2/year in the baseline 2.5° scenario—substantially greater than the emissions from these regions in previously published scenarios that would limit warming to 1.5°C or even 2°C. Such unanticipated emissions would in turn require non-emitting energy deployment from all sectors within these emerging emitters, and faster and deeper reductions in emissions from other countries to meet international climate goals. Moreover, the annual costs of keeping emissions at the low level are in many cases 0.2%–4.1% of countries’ gross domestic production, pointing to potential trade-offs with poverty-reduction goals and/or the need for economic support and low-carbon technology transfer from historically high-emitting countries. Our results thus highlight the critical importance of ramping up mitigation efforts in countries that to this point have been largely ignored.
Sick leave during pregnancy and occupational factors: a systematic review
Authors: Henrotin J B , Gulisano F 
Published: October 2022

AbstractBackgroundThe reported prevalence of sick leave (SL) during pregnancy is high among European pregnant workers (PW). The causes of SL during pregnancy are complex, and further research is necessary to explain their occurrence.AimsSummarize the evidence for an association between occupational risks for pregnancy and SL.MethodsA systematic review was conducted by two independent reviewers using PRISMA guidelines. Two databases (Pubmed, Embase) were interrogated between January 1990 and November 2021. The search question integrated key terms according to the PICOS acronym (free terms, MeSH, EMTREE). The quality of the selected studies was assessed according to the Methodological Index for Non-randomized Studies score.ResultsThis review assessed 11 epidemiological studies. Overall, the mean Methodological Index for Non-Randomized Studies score was 11, indicating moderate study quality. The results of the limited number of studies showed limited evidence for associations between psychosocial and physical work-related risk factors and the occurrence of SL among PW. However, this assessment was strengthened by the observation in several studies of a dose–response relationship between the number of occupational risks during pregnancy and SL.ConclusionsThe analysis of this review implicates PW’S exposure to occupational risks in the occurrence of SL. However, the few studies that support this conclusion have provided weak evidence; thus, further research is necessary.
Phenotypic Profile of Mycobacterium tuberculosis-Specific CD4 T-Cell Responses in People With Advanced Human Immunodeficiency Virus Who Develop Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome
Authors: Moseki Raymond M , Barber Daniel L , Du Bruyn Elsa , Shey Muki , Van der Plas Helen , Wilkinson Robert J , Meintjes Graeme , Riou Catherine 
Published: October 2022

Abstract

Background
Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a frequent complication of cotreatment for TB and human immunodeficiency virus (HIV)-1. We characterized Mycobacterium tuberculosis (Mtb)-specific CD4 T-cell phenotype and transcription factor profile associated with the development of TB-IRIS.

Methods
We examined the role of CD4 T-cell transcription factors in a murine model of mycobacterial IRIS. In humans, we used a longitudinal study design to compare the magnitude of antiretroviral therapy, activation, transcription factor profile, and cytotoxic potential of Mtb-specific CD4 T cells between TB-IRIS (n = 25) and appropriate non-IRIS control patients (n = 18) using flow cytometry.

Results
In the murine model, CD4 T-cell expression of Eomesodermin (Eomes), but not Tbet, was associated with experimentally induced IRIS. In patients, TB-IRIS onset was associated with the expansion of Mtb-specific IFNγ+CD4 T cells (P = .039). Patients with TB-IRIS had higher HLA-DR expression (P = .016), but no differences in the expression of T-bet or Eomes were observed. At TB-IRIS onset, Eomes+Tbet+Mtb-specific IFNγ+CD4+ T cells showed higher expression of granzyme B in patients with TB-IRIS (P = .026).

Conclusions
Although the murine model of Mycobacterium avium complex-IRIS suggests that Eomes+CD4 T cells underly IRIS, TB-IRIS was not associated with Eomes expression in patients. Mycobacterium tuberculosis-specific IFNγ+CD4 T-cell responses in TB-IRIS patients are differentiated, highly activated, and potentially cytotoxic.
Changes in phytoplankton community structure over a century in relation to environmental factors
Authors: Lundsør Elisabeth , Eikrem Wenche , Stige Leif Christian , Engesmo Anette , Stadniczeñko Sandra Gran , Edvardsen Bente 
Published: October 2022

Abstract
Changes in phytoplankton abundance and biomass during the period 1933–2020 were examined by statistical modeling using data from the Inner Oslofjorden phytoplankton database. The phytoplankton abundances increased with eutrophication from 1930s to 1970s, but with the implementation of sewage cleaning measures and a resulting reduction in nutrient releases, the phytoplankton abundance has since then decreased significantly. The onset of the seasonal blooms has started progressively later during the last 15 years, especially the spring bloom. The delayed spring bloom co-occurred with increasing temperature in winter and spring. The diatom biomass decreased more than that of dinoflagellates and other microeukaryotes. The diatom genus Skeletonema dominated the spring bloom and was found to be the key taxa in explaining these changes in abundance and phenology. Extensive summer blooms of the coccolithophore Emiliania huxleyi, which has been characteristic for the inner Oslofjorden, has also gradually decreased during the last decades, along with reducing eutrophication. Dinoflagellates have not had the same reduction in abundance as the other groups. Despite an increasing proportion of dinoflagellates compared with other taxa, there are no clear indications of increased occurrence of toxic algal blooms in inner Oslofjorden. However, the introduction of new “toxin-producing” species may cause concern.
CGL160-mediated recruitment of the coupling factor CF1 is required for efficient thylakoid ATP synthase assembly, photosynthesis, and chloroplast development in Arabidopsis
Authors: Reiter Bennet , Rosenhammer Lea , Marino Giada , Geimer Stefan , Leister Dario , Rühle Thilo 
Published: October 2022

Abstract
Chloroplast ATP synthases consist of a membrane-spanning coupling factor (CFO) and a soluble coupling factor (CF1). It was previously demonstrated that CONSERVED ONLY IN THE GREEN LINEAGE160 (CGL160) promotes the formation of plant CFO and performs a similar function in the assembly of its c-ring to that of the distantly related bacterial Atp1/UncI protein. Here, we show that in Arabidopsis (Arabidopsis thaliana) the N-terminal portion of CGL160 (AtCGL160N) is required for late steps in CF1-CFO assembly. In plants that lacked AtCGL160N, CF1-CFO content, photosynthesis, and chloroplast development were impaired. Loss of AtCGL160N did not perturb c-ring formation, but led to a 10-fold increase in the numbers of stromal CF1 subcomplexes relative to that in the wild type. Co-immunoprecipitation and protein crosslinking assays revealed an association of AtCGL160 with CF1 subunits. Yeast two-hybrid assays localized the interaction to a stretch of AtCGL160N that binds to the DELSEED-containing CF1-β subdomain. Since Atp1 of Synechocystis (Synechocystis sp. PCC 6803) could functionally replace the membrane domain of AtCGL160 in Arabidopsis, we propose that CGL160 evolved from a cyanobacterial ancestor and acquired an additional function in the recruitment of a soluble CF1 subcomplex, which is critical for the modulation of CF1-CFO activity and photosynthesis.
Optimal Corporate Taxation Under Financial Frictions
Authors: Dávila Eduardo , Hébert Benjamin 
Published: October 2022

Abstract
This article studies the optimal design of corporate taxes when firms have private information about future investment opportunities and face financial constraints. A government whose goal is to efficiently raise a given amount of revenue from its corporate sector should attempt to tax unconstrained firms, which value resources inside the firm less than financially constrained firms. We show that a corporate payout tax (a tax on dividends and share repurchases) can both separate constrained and unconstrained firms and raise revenue and is therefore optimal. Our quantitative analysis implies that a revenue-neutral switch from profit taxation to payout taxation would increase the overall value of existing firms and new entrants by $7\%$. This switch could be implemented in the current US tax system by making retained earnings fully deductible.
Effect of Hypoxia Preconditioning on the Regenerative Capacity of Adipose Tissue Derived Mesenchymal Stem Cells in a Model of Renal Artery Stenosis
Authors: Farooqui Naba , Mohan Arjunmohan , Isik Busra , Goksu Busra B , Thaler Roman , Zhu Xiang Yang , Krier James D , Saadiq Ishran M , Ferguson Christopher M , Jordan Kyra L , Tang Hui , Textor Stephen C , Hickson La Tonya J , van Wijnen Andre J , Eirin Alfonso , Lerman Lilach O , Herrmann Sandra M 
Published: October 2022

Abstract
Atherosclerotic renal artery stenosis (ARAS) is associated with irreversible parenchymal renal disease and regenerative stem cell therapies may improve renal outcomes. Hypoxia preconditioning (HPC) may improve the regenerative functions of adipose tissue-derived mesenchymal stem cells (AMSC) by affecting DNA 5-hydroxymethylcytosine (5hmC) marks in angiogenic genes. Here, we investigated using a porcine ARAS model, whether growth of ARAS AMSCs in hypoxia (Hx) versus normoxia (Nx) would enhance renal tissue repair, and comprehensively analyze how HPC modifies DNA hydroxymethylation compared to untreated ARAS and healthy/normal pigs (n=5 each). ARAS pigs exhibited elevated serum cholesterol, serum creatinine and renal artery stenosis, with a concomitant decrease in renal blood flow (RBF) and increased blood pressure (BP) compared to healthy pigs. Renal artery injection of either autologous Nx or Hx AMSCs improved diastolic BP, reduced kidney tissue fibrosis, and inflammation (CD3+ T-cells) in ARAS pigs. In addition, renal medullary hypoxia significantly lowered with Nx but not Hx AMSC treatment. Mechanistically, levels of epigenetic 5hmC marks (which reflect gene activation) estimated using DNA immunoprecipitation technique were elevated in profibrotic and inflammatory genes in ARAS compared with normal AMSCs. HPC significantly reduced 5hmC levels in cholesterol biosynthesis and oxidative stress response pathways in ARAS AMSCs. Thus, autologous AMSCs improve key renovascular parameters and inflammation in ARAS pigs, with HPC mitigating pathological molecular effects on inflammatory and profibrotic genes which may play a role in augmenting regenerative capacity of AMSCs.
Integrative transcriptome analysis reveals TEKT2 and PIAS2 involvement in diabetic nephropathy
Authors: Li Yuanqing , Lin Hongchun , Shu Shuangshuang , Sun Yuxiang , Lai Weiyan , Chen Wenfang , Hu Zhaoyong , Peng Hui 
Published: October 2022

AbstractCell heterogeneity has impeded the accurate interpretation of the bulk transcriptome data from patients with diabetic nephropathy (DN). We performed an analysis by integrating bulk and single‐cell transcriptome datasets to uncover novel mechanisms leading to DN, especially in the podocytes. Microdissected glomeruli and tubules transcriptome datasets were selected from Gene Expression Omnibus (GEO). Then the consistency between datasets was evaluated. The analysis of the bulk dataset and single‐nucleus RNA dataset was integrated to reveal the cell type‐specific responses to DN. The candidate genes were validated in kidney tissues from DN patients and diabetic mice. We compared 4 glomerular and 4 tubular datasets and found considerable discrepancies among datasets regarding the deferentially expressed genes (DEGs), involved signaling pathways, and the hallmark enrichment profiles. Deconvolution of the bulk data revealed that the variations in cell‐type proportion contributed greatly to this discrepancy. The integrative analysis uncovered that the dysregulation of spermatogenesis‐related genes, including TEKT2 and PIAS2, was involved in the development of DN. Importantly, the mRNA level of TEKT2 was negatively correlated with the mRNA levels of NPHS1 (r = −.66, p < .0001) and NPHS2 (r = −.85, p < .0001) in human diabetic glomeruli. Immunostaining confirmed that the expression of TEKT2 and PIAS2 were up‐regulated in podocytes of DN patients and diabetic mice. Knocking down TEKT2 resisted high glucose‐induced cytoskeletal remodeling and down‐regulation of NPHS1 protein in the cultured podocyte. In conclusion, the integrative strategy can help us efficiently use the publicly available transcriptomics resources. Using this approach and combining it with classical research methods, we identified TEKT2 and PIAS2, two spermatogenesis‐related genes involved in the pathogenesis of DN. Furthermore, TEKT2 is involved in this pathogenesis by regulating the podocyte cytoskeleton.
Protective role for C3aR in experimental chronic pyelonephritis
Authors: Zhao Shu‐Juan , Wu Kun‐Yi , Min Xiao‐Yun , Wang Chun‐Xuan , Cao Bo , Ma Ning , Yang Xue‐Ling , Zhu Zhuo‐Ran , Fu Rong‐Guo , Zhou Wuding , Yang Ju‐Rong , Li Ke 
Published: October 2022

AbstractEmerging evidence suggest that C3aR plays important roles in homeostasis, host defense and disease. Although it is known that C3aR is protective in several models of acute bacterial infections, the role for C3aR in chronic infection is largely unknown. Here we show that C3aR is protective in experimental chronic pyelonephritis. Global C3aR deficient (C3ar−/−) mice had higher renal bacterial load, more pronounced renal histological lesions, increased renal apoptotic cell accumulation, tissue inflammation and extracellular matrix deposition following renal infection with uropathogenic E. coli (UPEC) strain IH11128, compared to WT control mice. Myeloid C3aR deficient (Lyz2‐C3ar−/−) mice exhibited a similar disease phenotype to global C3ar−/− mice. Pharmacological treatment with a C3aR agonist reduced disease severity in experimental chronic pyelonephritis. Furthermore, macrophages of C3ar−/− mice exhibited impaired ability to phagocytose UPEC. Our data clearly demonstrate a protective role for C3aR against experimental chronic pyelonephritis, macrophage C3aR plays a major role in the protection, and C3aR is necessary for phagocytosis of UPEC by macrophages. Our observation that C3aR agonist curtailed the pathology suggests a therapeutic potential for activation of C3aR in chronic infection.
Referred sensation location can be altered by a strong heterotopic nociceptive stimulus: implications for clinical pain conditions
Authors: Salis Benedetta , Svensson Peter , Exposto Fernando G. 
Published: October 2022

Abstract
Referred sensations (RS) are a common clinical phenomenon in patients with musculoskeletal pain; however, the underlying mechanisms of RS and implications for diagnosis and management are poorly understood. The location of referral seems to have a preferred site, but studies have suggested it can be redirected to a site of previous injury and pain. However, it is not known if the same phenomenon can occur for a much shorter-lasting painful stimulus in the trigeminal system. The aim of this study was to assess if RS location elicited with standardized palpation of the masseter muscle could be altered following a 10-minute painful infusion of hypertonic saline into the retromolar region. A total of 56 healthy participants participated in this cross-over study performed in 2 sessions separated by 1 hour. At each session, baseline and postinfusion assessments of masseter muscle mechanical sensitivity were performed using 2 different forces (0.5 kg and 2 kg). Between assessments, hypertonic saline (5%) or isotonic saline (control) were continuously infused into the retromolar region. Participants were asked to rate their mechanical sensitivity and any RS they experienced as well as to draw the location of the RS. No difference in mechanical sensitivity or RS frequency was seen after either infusion when compared with before infusion. However, the RS location was displaced on average 1.2 cm between the baseline and postinfusion assessments for the hypertonic saline infusion, which was significantly increased when compared with the isotonic saline infusion which was on average 0.4 cm. These novel findings indicate the potential to modify the location of RS in the trigeminal system following a relatively brief noxious input. Clinicians need to be aware of the possible rerouting of RS in patients with complex orofacial pain.
Consensus and guidelines on lipoprotein(a) – seeing the forest through the trees
Authors: Kronenberg Florian , Mora Samia , Stroes Erik S.G. 
Published: October 2022

Purpose of the review
Over the past decade, lipoprotein(a) [Lp(a)] made it to several consensus and guideline documents. This review aims to summarize the literature which underlies the various recommendations and compares recent European and North American consensus and guideline documents of the recent 3–4 years.

Recent findings
Multiple large epidemiological and genetic studies have provided strong evidence for a causal association between Lp(a) concentrations and atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis. There is a dose-dependent linear relationship between Lp(a) and ASCVD risk advocating to consider Lp(a) on a continuous scale rather than using thresholds. The best way to implement this in the clinic is by individualizing the Lp(a)-related risk using tools such as the ‘Lp(a) risk calculator’ (http://www.lpaclinicalguidance.com) that takes into account the Lp(a) level in the context of an individual's traditional risk factors and global risk for ASCVD. There is growing agreement across the guidelines regarding the clinical utility of measuring Lp(a) and more recent expert groups advocate for a general screening approach applied to all adults. As long as the cardiovascular outcomes trials for specific Lp(a)-lowering drugs are in progress, the current management of patients with high Lp(a) should focus on the comprehensive management of all other modifiable ASCVD risk factors which can be therapeutically addressed as per guideline recommendations.

Summary
Since the contribution of high Lp(a) concentrations to global ASCVD risk has been underestimated in the past, a clear recommendation to measure Lp(a) at least once in a person's lifetime is imperative. Recent expert consensus recommendations provide clinicians with direction on how to manage the excess risk associated with elevated Lp(a) concentration by comprehensive and individualized management of modifiable ASCVD risk factors while awaiting the results of clinical trials of Lp(a) targeted therapies.
Can 18F-FDG-Positron Emission Tomography be a Prognostic Tool in Children With Rhabdomyosarcoma Treated With Definitive Radiotherapy?
Authors: Cheriyalinkal Parambil Badira , Shah Sneha , Prasad Maya , Vora Tushar , Laskar Siddhartha , Khanna Nehal , Qureshi Sajid , Ramadwar Mukta , Kembhavi Seema , Sankaran Hari , Rangarajan Venkatesh , Thakur Sonali , Chinnaswamy Girish 
Published: October 2022

Background:
Persisting residual masses at treatment completion are known in rhabdomyosarcoma (RMS) treated with definitive radiotherapy (RT) to the primary site, but their prognostic significance is uncertain. Tumor response as assessed by anatomic imaging is not prognostic and studies based on 18F-FDG-PET response are limited. We report the prognostic significance of persistent FDG-avidity in residual masses, assessed 3-month postdefinitive RT, in pediatric RMS.

Materials and Methods:
Children 15 years old or below with Group III/IV RMS who received only definitive radiotherapy for local control from June 2013 to December 2018, and had 18F-FDG-PET CT at 3 months post-RT were retrospectively analyzed for outcomes and other prognostic factors.

Results:
Sixty-three children were eligible (Group III-55, Group IV-8). 18F-FDG-PET CT scan done 3 months postradiotherapy showed FDG-avid residual masses in 10 patients (15.9%), anatomic residual in 24 (38.1%), and no anatomic/FDG-avid residual in 29(46.0%). At a median follow-up of 38 months (interquartile range, 24 to 55 mo), 3-year EFS of patients with FDG-avid residual masses was 40.0% (95% CI: 18.7% to 85.5%) versus the rest of the cohort, which was 71.9% (95% CI: 59.8% to 86.5%) (P=0.008). Three-year OS of patients with FDG-avid residual masses was 50.8% (95% CI: 25.7% to 100.0%) versus the rest of the cohort, which was 77.0% (95% CI: 65.1% to 91.0%) (P=0.037). Presence of FDG-avid residual disease persisting post-RT affected both EFS [HR-3.34 (95% CI: 1.29 to 8.68) (P=0.013)] and OS [HR-3.20 (95% CI: 1.01 to 10.12) (P=0.048)] on univariate analysis and this significance was retained for EFS in multivariate analysis [HR-3.52 (95% CI: 1.33 to 9.30) (P=0.011)].

Conclusions:
Persistent metabolic activity in residual disease post-chemoradiotherapy in RMS may portend a poorer prognosis with an increased risk of relapse. This subset of high-risk patients needs to be identified, and further trials are warranted to develop strategies to improve their outcomes.