bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted inhibition of Rev‐erb‐α/β limits ferroptosis to ameliorate folic acid‐induced acute kidney injury
Authors: Guo Lianxia , Zhang Tianpeng , Wang Fei , Chen Xun , Xu Haiman , Zhou Cui , Chen Min , Yu Fangjun , Wang Shuai , Yang Deguang , Wu Baojian 
Published: October 2020

Background and PurposeAcute kidney injury (AKI) is a common and critical illness, resulting in severe morbidity and a high mortality. There is a considerable interest in identifying novel molecular targets for management of AKI. We investigated the potential role of the circadian clock components Rev‐erb‐α/β in regulation of ferroptosis and AKI.Experimental ApproachAKI model was established by treating mice with folic acid. Regulatory effects of Rev‐erb‐α/β on AKI and ferroptosis were determined using single‐gene knockout (Rev‐erb‐α−/− and Rev‐erb‐β−/−) mice, incomplete double‐knockout (icDKO, Rev‐erb‐α+/− Rev‐erb‐β−/−) mice and cells with erastin‐induced ferroptosis. Targeted antagonism of Rev‐erb‐α/β to alleviate AKI and ferroptosis was assessed using the small‐molecule antagonist SR8278. Transcriptional gene regulation was investigated using luciferase reporter, mobility shift and chromatin immunoprecipitation assays.Key ResultsLoss of Rev‐erb‐α or Rev‐erb‐β reduced the sensitivity of mice to folic acid‐induced AKI and eliminated the circadian time dependency in disease severity. This coincided with less extensive ferroptosis, a main cause of folic acid‐induced AKI. Moreover, icDKO mice were more resistant to folic acid‐induced AKI and ferroptosis as compared with single‐gene knockout mice. Supporting this, targeting Rev‐erb‐α/β by SR8278 attenuated ferroptosis to ameliorate folic acid‐induced AKI in mice. Rev‐erb‐α/β promoted ferroptosis by repressing the transcription of Slc7a11 and HO1 (two ferroptosis‐inhibitory genes) via direct binding to a RORE cis‐element.Conclusion and ImplicationsTargeted inhibition of Rev‐erb‐α/β limits ferroptosis to ameliorate folic acid‐induced AKI in mice. The findings may have implications for improved understanding of circadian clock‐controlled ferroptosis and for formulating new strategies to treat AKI.
ZEB1 and oncogenic Ras constitute a regulatory switch for stimulus‐dependent E‐cadherin downregulation
Authors: Otake Shigeo , Itoh Yuka , Omata Chiho , Saitoh Masao , Miyazawa Keiji 
Published: October 2020

AbstractE‐cadherin, an epithelial cell–specific cell adhesion molecule, has both promoting and suppressing effects on tumor invasion and metastasis. It is often downregulated during cancer progression through gene deletion/mutation, transcriptional repression, or epigenetic silencing. We describe a novel regulatory switch to induce stimulus‐dependent downregulation of mRNA encoding E‐cadherin (CDH1 mRNA) in KRAS‐mutated cancer cells. The regulatory switch consists of ZEB1 and oncogenic K‐Ras, does not target the promoter region of CDH1, and requires an external cue to temporally downregulate E‐cadherin expression. Its repressive effect is maintained as long as the external stimulus continues and is attenuated with cessation of the stimulus. Contextual external cues that turn this regulatory switch on include activation of protein kinase C or fibroblast growth factor signaling. The mode of action is distinct from that of EPCAM repression by ZEB1, which does not require an external cue. Thus, KRAS‐mutated cancer cells acquire a novel mode of regulating E‐cadherin expression depending on ZEB1, which could contribute to phenotypic plasticity of cancer cells during malignant progression.
Oncogenic KRAS–expressing organoids with biliary epithelial stem cell properties give rise to biliary tract cancer in mice
Authors: Kasuga Akiyoshi , Semba Takashi , Sato Ryo , Nobusue Hiroyuki , Sugihara Eiji , Takaishi Hiromasa , Kanai Takanori , Saya Hideyuki , Arima Yoshimi 
Published: October 2020

AbstractBiliary tract cancer (BTC) arises from biliary epithelial cells (BECs) and includes intrahepatic cholangiocarcinoma (IHCC), gallbladder cancer (GC), and extrahepatic cholangiocarcinoma (EHCC). Although frequent KRAS mutations and epigenetic changes at the INK4A/ARF locus have been identified, the molecular pathogenesis of BTC is unclear and the development of corresponding anticancer agents remains inadequate. We isolated epithelial cell adhesion molecule (EpCAM)–positive BECs from the mouse intrahepatic bile duct, gallbladder, and extrahepatic bile duct, and established organoids derived from these cells. Introduction of activated KRAS and homozygous deletion of Ink4a/Arf in the cells of each organoid type conferred the ability to form lethal metastatic adenocarcinoma with differentiated components and a pronounced desmoplastic reaction on cell transplantation into syngeneic mice, indicating that the manipulated cells correspond to BTC–initiating cells. The syngeneic mouse models recapitulate the pathological features of human IHCC, GC, and EHCC, and they should therefore prove useful for the investigation of BTC carcinogenesis and the development of new therapeutic strategies. Tumor cells isolated from primary tumors formed organoids in three‐dimensional culture, and serial syngeneic transplantation of these cells revealed that their cancer stem cell properties were supported by organoid culture, but not by adherent culture. Adherent culture thus attenuated tumorigenic activity as well as the expression of both epithelial and stem cell markers, whereas the expression of epithelial‐mesenchymal transition (EMT)–related transcription factor genes and mesenchymal cell markers was induced. Our data show that organoid culture is important for maintenance of epithelial cell characteristics, stemness, and tumorigenic activity of BTC–initiating cells.
Bridging gaps in demographic analysis with phylogenetic imputation
Authors: James Tamora D. , Salguero‐Gómez Roberto , Jones Owen R. , Childs Dylan Z. , Beckerman Andrew P. 
Published: October 2020

AbstractPhylogenetically informed imputation methods have rarely been applied to estimate missing values in demographic data but may be a powerful tool for reconstructing vital rates of survival, maturation, and fecundity for species of conservation concern. Imputed vital rates could be used to parameterize demographic models to explore how populations respond when vital rates are perturbed. We used standardized vital rate estimates for 50 bird species to assess the use of phylogenetic imputation to fill gaps in demographic data. We calculated imputation accuracy for vital rates of focal species excluded from the data set either singly or in combination and with and without phylogeny, body mass, and life‐history trait data. We used imputed vital rates to calculate demographic metrics, including generation time, to validate the use of imputation in demographic analyses. Covariance among vital rates and other trait data provided a strong basis to guide imputation of missing vital rates in birds, even in the absence of phylogenetic information. Mean NRMSE for null and phylogenetic models differed by <0.01 except when no vital rates were available or for vital rates with high phylogenetic signal (Pagel'sλ >0.8). In these cases, including body mass and life‐history trait data compensated for lack of phylogenetic information: mean normalized root mean square error (NRMSE) for null and phylogenetic models differed by <0.01 for adult survival and <0.04 for maturation rate. Estimates of demographic metrics were sensitive to the accuracy of imputed vital rates. For example, mean error in generation time doubled in response to inaccurate estimates of maturation time. Accurate demographic data and metrics, such as generation time, are needed to inform conservation planning processes, for example through International Union for Conservation of Nature Red List assessments and population viability analysis. Imputed vital rates could be useful in this context but, as for any estimated model parameters, awareness of the sensitivities of demographic model outputs to the imputed vital rates is essential.
Increased arterial stiffness and reduced left ventricular long‐axis function in patients recovered from peripartum cardiomyopathy
Authors: Johansson Magnus C. , Barasa Anders , Basic Carmen , Nyberg Gunnar , Schaufelberger Maria 
Published: October 2020

AbstractBackgroundPeripartum cardiomyopathy (PPCM) is idiopathic pregnancy‐associated heart failure (HF) with reduced left ventricular ejection fraction (LVEF). We aimed to assess arterial stiffness and left ventricular (LV) function in women recovered from PPCM compared with controls.MethodsTwenty‐two PPCM patients were compared with 15 age‐matched controls with previous uncomplicated pregnancies. Eleven of the patients were at inclusion in the study recovered and off medication since at least 6 months and still free from cardiovascular symptoms with normal LVEF and normal NT‐proBNP. All underwent echocardiography, including LV strain, left atrial (LA) reservoir strain and tissue Doppler early diastolic velocity (e´) and non‐invasive assessment for arterial stiffness and central aortic systolic blood pressure (AoBP) at rest and immediately postexercise.ResultsThe patients off medication showed alterations compared with controls. AoBP was higher (120 ± 9 mm Hg vs. 104 ± 13 mm Hg; p = .001), a difference which persisted postexercise. The arterial elastance was higher (1.9 ± 0.4 mm Hg/ml vs. 1.3 ± 0.2 mm Hg/ml; p < .001), while there were lower e´ septal (8.9 ± 1.7 cm/s vs. 11.0 ± 1.1 cm/s; p = 0. 002), LV global strain (18.7 ± 3.9% vs. 23.1 ± 1.6%; p = .004) and LA reservoir strain (24.8 ± 9.1% vs. 37.7 ± 6.3%; p = .002).ConclusionsCompared with healthy controls, PPCM patients considered recovered and off medication had increased arterial stiffness, decreased LV longitudinal function and reduced LA function.
Spitz nevi in African Americans: A retrospective chart review of 11 patients
Authors: Farid Yostina I. , Honda Kord S. 
Published: October 2020

AbstractBackgroundSpitz nevi are benign melanocytic neoplasms that typically present as rapidly growing solitary lesions on the head, neck, or lower extremities. Very rare reports have been described in African Americans.MethodsA single‐institution 29‐year retrospective review of African American patients diagnosed with Spitz nevi was thoroughly analyzed in order to characterize these rare clinical and histopathologic presentations.ResultsEleven African Americans with spitzoid lesions were identified. Seven (64%) cases were in pediatric patients and nine (82%) were in females. Most lesions were hyperpigmented (73%) and elevated (82%). Six (55%) were compound Spitz nevi, three (27%) were dermal Spitz nevi, and two (18%) were junctional Spitz nevi. Two lesions had more than one atypical feature. Histopathologically, common features were symmetry, sharp circumscription, pagetoid spread (55%) with most being centrally, predominance of epithelioid cells (64%), Kamino bodies (45%), slight pigmentation (46%), maturation of dermal component with depth, and lack of subcutaneous fat involvement or ulceration. Excision was performed on all patients and there were no recurrences although follow‐up was limited.ConclusionAwareness of the possibility and various presentations of Spitz nevi in African Americans will help prevent misdiagnosis.
Malignant onychopapilloma
Authors: Haneke Eckart , Iorizzo Matilde , Gabutti Max , Beltraminelli Helmut 
Published: October 2020

AbstractOnychopapilloma is a fairly common lesion that is clinically typical enough to make the diagnosis. It is unique in that it stretches from the distal matrix all along the nailbed to the hyponychium. A case is described that developed pain eventually resulting in total excision. Histopathology revealed a malignant onychopapilloma. The differential diagnosis of this lesion is discussed.
Mechanisms underlying host persistence following amphibian disease emergence determine appropriate management strategies
Authors: Brannelly Laura A. , McCallum Hamish I. , Grogan Laura F. , Briggs Cheryl J. , Ribas Maria P. , Hollanders Matthijs , Sasso Thais , Familiar López Mariel , Newell David A. , Kilpatrick Auston M. 
Published: October 2020

AbstractEmerging infectious diseases have caused many species declines, changes in communities and even extinctions. There are also many species that persist following devastating declines due to disease. The broad mechanisms that enable host persistence following declines include evolution of resistance or tolerance, changes in immunity and behaviour, compensatory recruitment, pathogen attenuation, environmental refugia, density‐dependent transmission and changes in community composition. Here we examine the case of chytridiomycosis, the most important wildlife disease of the past century. We review the full breadth of mechanisms allowing host persistence, and synthesise research on host, pathogen, environmental and community factors driving persistence following chytridiomycosis‐related declines and overview the current evidence and the information required to support each mechanism. We found that for most species the mechanisms facilitating persistence have not been identified. We illustrate how the mechanisms that drive long‐term host population dynamics determine the most effective conservation management strategies. Therefore, understanding mechanisms of host persistence is important because many species continue to be threatened by disease, some of which will require intervention. The conceptual framework we describe is broadly applicable to other novel disease systems.
Serum S100A12 levels: Possible association with skin sclerosis and interstitial lung disease in systemic sclerosis
Authors: Omatsu Jun , Saigusa Ryosuke , Miyagawa Takuya , Fukui Yuki , Toyama Satoshi , Awaji Kentaro , Ikawa Tetsuya , Norimatsu Yuta , Yoshizaki Ayumi , Sato Shinichi , Asano Yoshihide 
Published: October 2020

AbstractDamage‐associated molecular patterns (DAMPs) have drawn much attention as a member of disease‐associated molecules in systemic sclerosis (SSc). In this study, we investigated the potential contribution of S100A12, a member of DAMPs, to the development of SSc by evaluating S100A12 expression in the lesional skin and the clinical correlation of serum S100A12 levels. S100A12 expression was markedly elevated in the epidermis of SSc‐involved skin at protein levels and in the bulk skin at mRNA levels. The deficiency of transcription factor Fli1, a predisposing factor of SSc, enhanced S100A12 expression and Fli1 occupied the S100A12 promoter in normal human keratinocytes. Serum S100A12 levels were higher in SSc patients, especially in those with diffuse cutaneous involvement, than in healthy controls and positively correlated with skin score. Furthermore, the presence of interstitial lung disease significantly augmented serum levels of S100A12. Importantly, serum S100A12 levels correlated inversely with both per cent forced vital capacity and per cent diffusing capacity for carbon monoxide and positively with serum levels of KL‐6 and surfactant protein‐D. Collectively, these results indicate a possible contribution of S100A12 to skin sclerosis and interstitial lung disease associated with SSc, further supporting the critical roles of DAMPs in the pathogenesis of this disease.
Resource‐use, body condition and parasite load metrics indicate contrasting health of stocked and native game fishes in Canadian prairie lakes
Authors: Nanayakkara Lushani , Starks Elizabeth R. , Cooper Ryan N. , Chow Sydney , Leavitt Peter R. , Wissel Björn 
Published: October 2020

AbstractThis study evaluated the status of native and stocked fish species in 13 prairie lakes in central Canada over eight years (2007–14) using three metrics: resource‐use (benthic versus pelagic carbon via stable isotopes); body condition (relative weight index Wr); and parasite load (cestode gut enumerations). Analyses included game and non‐game fishes, like naturally occurring northern pike, Esox lucius L., and yellow perch, Perca flavescens Mitchill, but focused on stocked walleye, Sander vitreus (Mitchill) because it supports a robust recreational fishery. Walleye and northern pike were significantly more reliant on benthic carbon than yellow perch or forage fishes (p < 0.05), but this reliance was not associated with any measured environmental variables for any species. In lakes with game fishes, forage fishes exhibited higher reliance on benthic energy, possibly due to predator avoidance strategy, particularly yellow perch. Walleye body condition index was consistently lower (<95–105) than values exhibited by the other two game fishes (81–139), and parasites were only common in walleye and associated with lake‐water salinity (r2 = 0.93, p < 0.05) and sex (p < 0.05). Based on the results, the most desirable game fish, walleye, appears less resilient to environmental variability than northern pike and yellow perch, making this species more susceptible to impacts of future climate change.
Change in fisheries access arrangements as a result of hydropower development: The case of reservoir fisheries at the Mount Coffee hydropower scheme in Liberia
Authors: Sharkey William , Arthur Robert I. , Daniels Roosevelt 
Published: October 2020

AbstractHydropower development can result in both environmental and social change. Modification of riparian environments and the creation of storage reservoirs can alter fish assemblages, change access arrangements and create new opportunities within and outside fishing. These opportunities may be perceived differently by different stakeholders, leading to changes in the fishery and, ultimately, with implications for the nature and distribution of benefits from the fishery. Focusing on a trap fishery for freshwater prawn Macrobrachium vollenhovenii (Herklots), this study examines the way access arrangements changed in response to the rehabilitation of the Mount Coffee run‐of‐river hydropower scheme on the lower reaches of the Saint Paul River in Liberia. Through the use of interviews and limited participant observation, the study explores the responses to change resulting from the rehabilitation, highlighting the way that agency and bargaining power contributed to shaping the formation of a fisher group and the new access arrangements that they have begun to develop.
Distribution, sources, and decomposition of soil organic matter along a salinity gradient in estuarine wetlands characterized by C:N ratio, δ13C‐δ15N, and lignin biomarker
Authors: Xia Shaopan , Song Zhaoliang , Li Qiang , Guo Laodong , Yu Changxun , Singh Bhupinder Pal , Fu Xiaoli , Chen Chunmei , Wang Yidong , Wang Hailong 
Published: October 2020

AbstractDespite increasing recognition of the critical role of coastal wetlands in mitigating climate change, sea‐level rise, and salinity increase, soil organic carbon (SOC) sequestration mechanisms in estuarine wetlands remain poorly understood. Here, we present new results on the source, decomposition, and storage of SOC in estuarine wetlands with four vegetation types, including single Phragmites australis (P, habitat I), a mixture of P. australis and Suaeda salsa (P + S, habitat II), single S. salsa (S, habitat III), and tidal flat (TF, habitat IV) across a salinity gradient. Values of δ13C increased with depth in aerobic soil layers (0–40 cm) but slightly decreased in anaerobic soil layers (40–100 cm). The δ15N was significantly enriched in soil organic matter at all depths than in the living plant tissues, indicating a preferential decomposition of 14N‐enriched organic components. Thus, the kinetic isotope fractionation during microbial degradation and the preferential substrate utilization are the dominant mechanisms in regulating isotopic compositions in aerobic and anaerobic conditions, respectively. Stable isotopic (δ13C and δ15N), elemental (C and N), and lignin composition (inherited (Ad/Al)s and C/V) were not completely consistent in reflecting the differences in SOC decomposition or accumulation among four vegetation types, possibly due to differences in litter inputs, root distributions, substrate quality, water‐table level, salinity, and microbial community composition/activity. Organic C contents and storage decreased from upstream to downstream, likely due to primarily changes in autochthonous sources (e.g., decreased onsite plant biomass input) and allochthonous materials (e.g., decreased fluvially transported upland river inputs, and increased tidally induced marine algae and phytoplankton). Our results revealed that multiple indicators are essential to unravel the degree of SOC decomposition and accumulation, and a combination of C:N ratios, δ13C, δ15N, and lignin biomarker provides a robust approach to decipher the decomposition and source of sedimentary organic matter along the river‐estuary‐ocean continuum.
Women and burnout in the context of a pandemic
Authors: Aldossari Maryam , Chaudhry Sara 
Published: October 2020

AbstractThis article presents the lived narrative of a female academic with children working in a British university and trying to cope with a completely new way of work and life in the context of the pandemic. The overall aim of the article is to offer a gendered account of burnout—specifically how women may be experiencing burnout at multiple levels, and the efficacy of their subsequent coping strategies. The narrative provides insights into how a range of coping mechanisms such as disengagement, denial, and energy conservation are deployed to deal with the increased responsibilities at work and home as a result of the pandemic. Existing research has viewed burnout as gender neutral, leaving a gap in the literature on the significant differences in both men's and women's experience of burnout as well as their coping behaviors.
Antimicrobial resistance of Helicobacter pylori in an eastern German region
Authors: Hofreuter Dirk , Behrendt Johannes , Franz Annett , Meyer Jens , Jansen Anna , Bluemel Benjamin , Eisele Bianca , Koken Miriam , Glocker Erik‐Oliver 
Published: October 2020

AbstractBackgroundAntimicrobial therapy is recommended to eradicate Helicobacter (H.) pylori in infected individuals. As first‐line treatments are empiric, knowledge of antimicrobial resistance is key to successful eradication.AimsWe investigated primary resistance in an eastern German region to derive recommendations for eradication treatment.MethodsWe used molecular genetic methods to examine Helicobacter rapid urease test (RUT) positive gastric specimens of 533 patients from Berlin and the federal state of Brandenburg with allegedly no prior eradication treatment. Tissue samples were removed from RUT and screened by real‐time PCR for mutations conferring resistance to clarithromycin. In addition, 182 samples out of 533 were tested for resistance to levofloxacin and tetracycline.ResultsPrimary resistances were 10.9% (58 out of 533) to clarithromycin; 13.7% (25/182) to levofloxacin; and 2.2% to tetracycline (4/182). Combined resistance to clarithromycin/levofloxacin was low (2.2%, 4/182). Female sex was significantly associated with clarithromycin resistance.ConclusionClarithromycin may be a suitable first‐line antibiotic for about 90% of outpatients. A simple molecular test may help physicians avoid prescription of an ineffective first‐line regimen.