bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interactive effect of the empirical lifestyle index for insulin resistance with the common genetic susceptibility locus rs2423279 for colorectal cancer
Authors: Kim Jimi , Lee Jeonghee , Oh Jae Hwan , Chang Hee Jin , Sohn Dae Kyung , Shin Aesun , Kim Jeongseon 
Published: April 2022

AbstractThe aim of this study is to examine the empirical insulinemic potential consisting of dietary and lifestyle factors and the interactive effect with the common genetic susceptibility locus rs2423279 on the risk of colorectal cancer (CRC). This case–control study was conducted with 923 CRC patients and 1846 controls. The empirical measures for assessing the insulinemic potential, namely, the empirical dietary index for hyperinsulinemia (EDIH), for insulin resistance (EDIR), the empirical lifestyle index for hyperinsulinemia (ELIH), and for insulin resistance (ELIR), were calculated based on semiquantitative food frequency questionnaire and lifestyle questionnaire. A genetic variant of rs2423279 was genotyped. The CRC patients were more likely to score in the highest quartile for the ELIH (OR 2·90, Q4 v. Q1, 95 % CI (2·01, 4·19), Pfor trend < 0·001), EDIR (OR 3·32, Q4 v. Q1, 95 % CI (2·32, 4·74), P < 0·001) and ELIR (OR 2·79, Q4 v. Q1, 95 % CI (1·96, 3·97), P < 0·001) than the controls. The significant effect between the ELIR, which assesses dietary and lifestyle patterns related to insulin resistance, and C allele carriers of rs2423279 was stronger than that for homozygous T allele carriers (OR 2·50, 95 % CI (1·78, 3·51), Pfor interaction = 0·034). The empirical insulinemic potential for insulin resistance might have interactive effects with the rs2423279 polymorphism on the risk of CRC. The results of this study suggest the basis of the metabolic impact of the insulin response on colorectal carcinogenesis.
The impact of dietary calcium content on phosphorus absorption and retention in growing pigs is enhanced by dietary microbial phytase supplementation
Authors: Hu Yixin , Hendriks Wouter , van Baal Jurgen , Resink Jan-Willem , Rodehutscord Markus , Van Krimpen Marinus M. , Bikker Paul 
Published: April 2022

AbstractSixty growing male pigs were used to test the hypothesis that high dietary Ca content reduces P absorption to a greater extent in microbial phytase-supplemented diets via reducing inositol phosphate (IP) degradation and enhancing P precipitation. Pigs were equally allotted over diets with three Ca contents 2·0, 5·8 and 9·6 g/kg with or without microbial phytase (0 v. 500 FTU/kg) in a 2 × 3 factorial arrangement. Faeces and urine were collected at the end of the 21-d experimental period. Subsequently, pigs were euthanised and digesta quantitatively collected from different gastrointestinal tract (GIT) segments. Increasing dietary Ca content reduced apparent P digestibility in all GIT segments posterior to the stomach (P < 0·001), with greater effect in phytase-supplemented diets in the distal small intestine (Pinteraction = 0·007) and total tract (Pinteraction = 0·023). Nonetheless, increasing dietary Ca to 5·8 g/kg enhanced P retention, but only in phytase-supplemented diets. Ileal IP6 degradation increased with phytase (P < 0·001) but decreased with increasing dietary Ca content (P = 0·014). Proportion of IP esters in total IP (∑IP) indicated that IP6/∑IP was increased while IP4/∑IP and IP3/∑IP were reduced with increasing dietary Ca content and also with a greater impact in phytase-supplemented diets (Pinteraction = 0·025, 0·018 and 0·009, respectively). In all GIT segments, P solubility was increased with phytase (P < 0·001) and tended to be reduced with dietary Ca content (P < 0·096). Measurements in GIT segments showed that increasing dietary Ca content reduced apparent P digestibility via reducing IP degradation and enhancing P precipitation, with a greater impact in phytase-supplemented diets due to reduced IP degradation.
Transition rather than Revolution: The Gradual Road towards Animal Legal Personhood through the Legislature
Authors: Bernet Kempers Eva 
Published: April 2022

AbstractIt is sometimes assumed that, in order for animals to be adequately protected by the legal system, their status first needs to change from property to person in one fell swoop. Legal personhood is perceived as the necessary requirement for animals to possess legal rights and become visible in law, distinguished from legal things. In this article I propose an alternative approach to animal legal personhood, which construes the road towards it as a gradual transition rather than a revolution. According to this alternative approach, animals become increasingly visible in law when their existing simple rights are shaped to function more like the rights of humans. Instead of a condition for the possession of rights, legal personhood should then be regarded as a (potential) consequence of growing animal rights.
Benzobicyclon efficacy is affected by plant growth stage, HPPD Inhibitor Sensitive 1 (HIS1) expression and zygosity in weedy rice (Oryza sativa)
Authors: Brabham Chad , Norsworthy Jason K. , Sha Xueyan , Varanasi Vijay K. , González-Torralva Fidel 
Published: April 2022

AbstractBenzobicyclon tolerance in rice (Oryza sativa L.) is dependent on the presence of a functional HIS1 gene, but the level of sensitivity might vary among different cultivars. Greenhouse, laboratory, and field experiments were conducted to further explore the role of HIS1 in cultivated rice tolerance and to exploit findings toward optimizing benzobicyclon activity on weedy rice (unwanted rice; Oryza sativa L.). In a heredity experiment, benzobicyclon tolerance was confirmed to be a semidominant trait conferred by HIS1 based on the intermediate response (ED50 values) of HIS1 heterozygous F1 plants. The spatial–temporal expression of HIS1 was next studied in tissue types (blades, sheaths, and whorls) across tolerant cultivars (‘Roy J’, ‘Diamond’, ‘LaKast’, ‘CLXL745’, and ‘XL753’) and growth stages (2- to 3- compared with 5- to 6-leaf). The relative expression of HIS1 was tissue specific and highest in whorls, followed by blades and then sheaths. Minimal differences in expression across cultivars and growth stages were observed. Furthermore, HIS1 was not largely upregulated at 6 h after benzobicyclon treatment. In the same experiment, cultivar tolerance to benzobicyclon at the label rate of 371 g ha−1 was found to be growth stage dependent. Plant growth was reduced by ∼35% when rice plants were at the 2- to 3- compared with 5- to 6-leaf growth stages. These results show that differences in benzobicyclon tolerance among HIS1 homozygous cultivars is likely not directly correlated with the expression of HIS1. In this research a model was proposed and supported by a field proof of concept study, indicating benzobicyclon efficacy on weedy rice is a function of HIS1 zygosity by growth stage at application. Prior research indicates HIS1 is the dominant allele in weedy rice accessions in Arkansas, and thus, based on our model, benzobicyclon should be applied to weedy rice with ≤2 leaves for suppression.
Relative Humidity Dependence of Hygroscopicity Parameter of Ambient Aerosols
Authors: Zhao Pusheng , Ge Shuangshuang , Su Jie , Ding Jing , Kuang Ye 
Published: April 2022

AbstractThe hygroscopicity parameter (κ) has been widely used in studies of aerosol hygroscopic growth and cloud condensation nucleus activation, but the effect of relative humidity (RH) variations on ambient aerosol hygroscopicity is rarely discussed and is often ignored in the application of κ‐Köhler theory. In this study, an improved humidified nephelometer system was used to measure the scattering enhancement (f(RH)) of bulk aerosols and the RH‐dependent κ was derived. It was found that the κ of both pure inorganic water‐soluble electrolytes and ambient aerosols is significantly RH‐dependent. The particle size had a great influence on f(RH), but κ had no obvious size dependence. Compared with using the RH‐dependent κ, the scattering coefficient of ambient aerosols with the fixed κ value would produce a relative error of −10%–25%. Parameterization schemes of RH‐dependent κ of ambient aerosols were established, which could serve as a reference for the future research.
Strategic Plan for the Journal of Geophysical Research—Earth Surface
Authors: East Amy E. , Attal Mikael , Hoitink A. J. F. (Ton) , Sergienko Olga V. 
Published: April 2022

AbstractThe Editors of the Journal of Geophysical Research—Earth Surface present a new strategic plan for the journal. The journal will contribute to the objectives of AGU to embrace advancing Earth and space science for the benefit of human societies and the environment, while continuing to value fundamental science deeply. Many scientific topics covered by JGR Earth Surface are closely connected to urgent, complex problems affecting humanity and the global environment today, including climate change and a variety of natural hazards; this strategic plan is intended to ensure that published science is robust, impactful, and ultimately used to help address those problems. The plan prioritizes (1) publishing high‐impact science using the highest standards of scientific ethics and rigor; (2) advancing mechanistic understanding needed to address societal challenges; and (3) ensuring that a diverse talent pool contributes to the science through a fair, equitable review and publication process.
Detrimental effects of branched-chain amino acids in glucose tolerance can be attributed to valine induced glucotoxicity in skeletal muscle
Authors: Bishop Christopher A. , Machate Tina , Henning Thorsten , Henkel Janin , Püschel Gerhard , Weber Daniela , Grune Tilman , Klaus Susanne , Weitkunat Karolin 
Published: April 2022

Abstract
Objective
Current data regarding the roles of branched-chain amino acids (BCAA) in metabolic health are rather conflicting, as positive and negative effects have been attributed to their intake.

Methods
To address this, individual effects of leucine and valine were elucidated in vivo (C57BL/6JRj mice) with a detailed phenotyping of these supplementations in high-fat (HF) diets and further characterization with in vitro approaches (C2C12 myocytes).

Results
Here, we demonstrate that under HF conditions, leucine mediates beneficial effects on adiposity and insulin sensitivity, in part due to increasing energy expenditure—likely contributing partially to the beneficial effects of a higher milk protein intake. On the other hand, valine feeding leads to a worsening of HF-induced health impairments, specifically reducing glucose tolerance/insulin sensitivity. These negative effects are driven by an accumulation of the valine-derived metabolite 3-hydroxyisobutyrate (3-HIB). Higher plasma 3-HIB levels increase basal skeletal muscle glucose uptake which drives glucotoxicity and impairs myocyte insulin signaling.

Conclusion
These data demonstrate the detrimental role of valine in an HF context and elucidate additional targetable pathways in the etiology of BCAA-induced obesity and insulin resistance.
Suppression of mutant Kirsten-RAS (KRASG12D)-driven pancreatic carcinogenesis by dual-specificity MAP kinase phosphatases 5 and 6
Authors: Kidger Andrew M. , Saville Mark K. , Rushworth Linda K. , Davidson Jane , Stellzig Julia , Ono Motoharu , Kuebelsbeck Ludwig A. , Janssen Klaus-Peter , Holzmann Bernhard , Morton Jennifer P. , Sansom Owen J. , Caunt Christopher J. , Keyse Stephen M. 
Published: April 2022

AbstractThe cytoplasmic phosphatase DUSP6 and its nuclear counterpart DUSP5 are negative regulators of RAS/ERK signalling. Here we use deletion of either Dusp5 or Dusp6 to explore the roles of these phosphatases in a murine model of KRASG12D-driven pancreatic cancer. By 56-days, loss of either DUSP5 or DUSP6 causes a significant increase in KRASG12D-driven pancreatic hyperplasia. This is accompanied by increased pancreatic acinar to ductal metaplasia (ADM) and the development of pre-neoplastic pancreatic intraepithelial neoplasia (PanINs). In contrast, by 100-days, pancreatic hyperplasia is reversed with significant atrophy of pancreatic tissue and weight loss observed in animals lacking either DUSP5 or DUSP6. On further ageing, Dusp6−/− mice display accelerated development of metastatic pancreatic ductal adenocarcinoma (PDAC), while in Dusp5−/− animals, although PDAC development is increased this process is attenuated by atrophy of pancreatic acinar tissue and severe weight loss in some animals before cancer could progress. Our data suggest that despite a common target in the ERK MAP kinase, DUSP5 and DUSP6 play partially non-redundant roles in suppressing oncogenic KRASG12D signalling, thus retarding both tumour initiation and progression. Our data suggest that loss of either DUSP5 or DUSP6, as observed in certain human tumours, including the pancreas, could promote carcinogenesis.
Global characterization of extrachromosomal circular DNAs in advanced high grade serous ovarian cancer
Authors: Cen Yixuan , Fang Yifeng , Ren Yan , Hong Shiyuan , Lu Weiguo , Xu Junfen 
Published: April 2022

AbstractHigh grade serous ovarian cancer (HGSOC) is the most aggressive subtype of ovarian cancer and HGSOC patients often appear with metastasis, leading to the poor prognosis. Up to date, the extrachromosomal circular DNAs (eccDNAs) have been shown to be involved in cancer genome remodeling but the roles of eccDNAs in metastatic HGSOC are still not clear. Here we explored eccDNA profiles in HGSOC by Circle-Sequencing analysis using four pairs of primary and metastatic tissues of HGSOC patients. Within the differentially expressed eccDNAs screened out by our analysis, eight candidates were validated by outward PCR and qRT-PCR analysis. Among them, DNMT1circle10302690-10302961 was further confirmed by FISH assay and BaseScope assay, as the most significantly down-regulated eccDNA in metastatic tumors of HGSOC. Lower expression of DNMT1circle10302690-10302961 in both primary and metastatic tumors was associated with worse prognosis of HGSOC. Taken together, our finding firstly demonstrated the eccDNAs landscape of primary and metastatic tissues of HGSOC. The eccDNA DNMT1circle10302690-10302961 can be considered as a potential biomarker or a therapeutically clinical target of HGSOC metastasis and prognosis.
Long noncoding RNA LINC00857 promotes pancreatic cancer proliferation and metastasis by regulating the miR-130b/RHOA axis
Authors: Chen Peng , Zeng Zhirui , Wang Jie , Cao Wenpeng , Song Chunzhuo , Lei Shan , Li Yichuan , Ren Zhangxia 
Published: April 2022

AbstractDysregulation of long noncoding RNAs (lncRNAs) is involved in the pathogenesis and progression of pancreatic cancer (PC). In the current study, we investigated the role and molecular mechanism of LINC00857 in PC. The expression of LINC00857 in PC was analyzed by bioinformatics analysis and qRT-PCR, and the relationship between LINC00857 expression and clinical characteristics of patients of PC was analyzed by Fisher’s exact test. Gain- and loss-of-function assays were performed to determine the biological function of LINC00857 in PC. The relationship between LINC00857, miR-130b, and RHOA were determined by RNA pull-down assay, luciferase assay, and qRT-PCR. Our results demonstrated that LINC00857 expression was elevated in PC, and high expression of LINC00857 was positively associated with tumor diameter, T stage, and lymph node metastasis. LINC00857 promoted the proliferation and mobility of PC cells in vitro and in vivo. Mechanistically, LINC00857 acts as a sponge for miR-130b and decreases its expression. miR-130b exhibits tumor suppressor functions in PC, and RHOA was identified as the key target gene of miR-130b. The functions induced by LINC00857 in PC cells were dependent on the miR-130b/RHOA axis. In conclusion, the current study indicated that LINC00857 promotes PC tumorigenesis and metastasis by modulating the miR-130b/RHOA axis, implying that LINC00857 might be a new therapeutic target for PC.
Clitoral reconstruction: challenges and new directions
Authors: Villani Michela 
Published: April 2022

AbstractClitoral reconstruction (CR) has been the subject of several studies in recent years, mainly in the medical field. Women with female genital mutilation or cutting (FGM/C) seek clitoral reconstructive surgery to improve their sexual well-being, but also because they are affected by poor self- and body image. CR is supposed to help women with FGM/C reconstruct their sense of self, but the benefits and risks of this surgery have not been sufficiently explored. There are currently no recommendations supporting CR from mainstream medical bodies, and there have been very few ethical studies of the procedure. This article critically discusses the principal studies produced in the medical field and available reflections produced in the social sciences. Through the theoretical frameworks of postcolonial and feminist studies, the article discusses sexuality and pleasure, gender and identity, and race and positionality, with the aim of promoting collaborative work on CR between researchers and social and health professionals.
Data-driven learning how oncogenic gene expression locally alters heterocellular networks
Authors: Klinke David J. , Fernandez Audry , Deng Wentao , Razazan Atefeh , Latifizadeh Habibolla , Pirkey Anika C. 
Published: April 2022

AbstractDeveloping drugs increasingly relies on mechanistic modeling and simulation. Models that capture causal relations among genetic drivers of oncogenesis, functional plasticity, and host immunity complement wet experiments. Unfortunately, formulating such mechanistic cell-level models currently relies on hand curation, which can bias how data is interpreted or the priority of drug targets. In modeling molecular-level networks, rules and algorithms are employed to limit a priori biases in formulating mechanistic models. Here we combine digital cytometry with Bayesian network inference to generate causal models of cell-level networks linking an increase in gene expression associated with oncogenesis with alterations in stromal and immune cell subsets from bulk transcriptomic datasets. We predict how increased Cell Communication Network factor 4, a secreted matricellular protein, alters the tumor microenvironment using data from patients diagnosed with breast cancer and melanoma. Predictions are then tested using two immunocompetent mouse models for melanoma, which provide consistent experimental results.
Presenilin 2 N141I mutation induces hyperactive immune response through the epigenetic repression of REV-ERBα
Authors: Nam Hyeri , Lee Younghwan , Kim Boil , Lee Ji-Won , Hwang Seohyeon , An Hyun-Kyu , Chung Kyung Min , Park Youngjin , Hong Jihyun , Kim Kyungjin , Kim Eun-Kyoung , Choe Han Kyoung , Yu Seong-Woon 
Published: April 2022

AbstractHyperimmunity drives the development of Alzheimer disease (AD). The immune system is under the circadian control, and circadian abnormalities aggravate AD progress. Here, we investigate how an AD-linked mutation deregulates expression of circadian genes and induces cognitive decline using the knock-in (KI) mice heterozygous for presenilin 2 N141I mutation. This mutation causes selective overproduction of clock gene-controlled cytokines through the DNA hypermethylation-mediated repression of REV-ERBα in innate immune cells. The KI/+ mice are vulnerable to otherwise innocuous, mild immune challenges. The antipsychotic chlorpromazine restores the REV-ERBα level by normalizing DNA methylation through the inhibition of PI3K/AKT1 pathway, and prevents the overexcitation of innate immune cells and cognitive decline in KI/+ mice. These results highlight a pathogenic link between this AD mutation and immune cell overactivation through the epigenetic suppression of REV-ERBα.
Construction of a two-dimensional artificial antioxidase for nanocatalytic rheumatoid arthritis treatment
Authors: Yang Bowen , Yao Heliang , Yang Jiacai , Chen Chang , Shi Jianlin 
Published: April 2022

AbstractConstructing nanomaterials mimicking the coordination environments of natural enzymes may achieve biomimetic catalysis. Here we construct a two-dimensional (2D) metal-organic framework (MOF) nanosheet catalyst as an artificial antioxidase for nanocatalytic rheumatoid arthritis treatment. The 2D MOF periodically assembles numbers of manganese porphyrin molecules, which has a metal coordination geometry analogous to those of two typical antioxidases, human mitochondrial manganese superoxide dismutase (Mn-SOD) and human erythrocyte catalase. The zinc atoms of the 2D MOF regulate the metal-centered redox potential of coordinated manganese porphyrin ligand, endowing the nanosheet with both SOD- and catalase-like activities. Cellular experiments show unique anti-inflammatory and pro-biomineralization performances of the 2D MOF, while in vivo animal model further demonstrates its desirable antiarthritic efficacy. It is expected that such a nanocatalytic antioxidation concept may provide feasible approaches to future anti-inflammatory treatments.
The impact of reproductive factors on DNA methylation-based telomere length in healthy breast tissue
Authors: Sehl Mary E. , Henry Jill E. , Storniolo Anna Maria , Horvath Steve , Ganz Patricia A. 
Published: April 2022

AbstractEstrogen promotes breast tissue proliferation and telomerase activation. We investigated the effects of reproductive history on cell cycling and telomere length using a DNA methylation-based estimate of telomere length (DNAmTL) in breast and blood from healthy women donors. We demonstrate that DNAmTL is shorter in breast than in blood, and that nulliparous women have longer age-adjusted DNAmTL in both breast and blood, potentially explaining their higher risk of breast cancer.
LINC00355 regulates p27KIP expression by binding to MENIN to induce proliferation in late-stage relapse breast cancer
Authors: Eteleeb Abdallah M. , Thunuguntla Prasanth K. , Gelev Kyla Z. , Tang Cynthia Y. , Rozycki Emily B. , Miller Alexander , Lei Jonathan T. , Jayasinghe Reyka G. , Dang Ha X. , White Nicole M. , Reis-Filho Jorge S. , Mardis Elaine R. , Ellis Matthew J. , Ding Li , Silva-Fisher Jessica M. , Maher Christopher A. 
Published: April 2022

AbstractLate-stage relapse (LSR) in patients with breast cancer (BC) occurs more than five years and up to 10 years after initial treatment and has less than 30% 5-year relative survival rate. Long non-coding RNAs (lncRNAs) play important roles in BC yet have not been studied in LSR BC. Here, we identify 1127 lncRNAs differentially expressed in LSR BC via transcriptome sequencing and analysis of 72 early-stage and 24 LSR BC patient tumors. Decreasing expression of the most up-regulated lncRNA, LINC00355, in BC and MCF7 long-term estrogen deprived cell lines decreases cellular invasion and proliferation. Subsequent mechanistic studies show that LINC00355 binds to MENIN and changes occupancy at the CDKN1B promoter to decrease p27Kip. In summary, this is a key study discovering lncRNAs in LSR BC and LINC00355 association with epigenetic regulation and proliferation in BC.