bluuebunny/crossref_metadata_2025_split huggingface dataset:
The consequences of claiming Social Security benefits at age 62
Authors: Armour Philip , Knapp David 
Published: October 2021

AbstractDelaying claiming of Social Security old-age benefits past the earliest eligibility age, age 62, raises the monthly benefit for a person's life. Despite arguments from both proponents and opponents of delayed claiming in academia and public discourse, little is known about whether claiming decisions lead to substantively different outcomes. We compare differences in outcomes between age-62 claimants and otherwise similar later claimants that are matched on health, employment, and financial characteristics at age 60. We find that age-62 claimers are substantially less likely to work after 62 and have persistently lower income into their 70s. Differences in assets emerged in the 70s, with early claimants having lower wealth, but we find no differences in mortality or self-reported financial hardship. The difference in wealth is driven primarily by a growth in wealth among later claimants rather than substantial decumulation by age-62 claimants.
AUTOMORPHIC LEFSCHETZ PROPERTIES FOR NONCOMPACT ARITHMETIC MANIFOLDS
Authors: Nair Arvind N. , Rai Ankit 
Published: October 2021

AbstractWe prove the injectivity of Oda-type restriction maps for the cohomology of noncompact congruence quotients of symmetric spaces. This includes results for restriction between (1) congruence real hyperbolic manifolds, (2) congruence complex hyperbolic manifolds, and (3) orthogonal Shimura varieties. These results generalize results for compact congruence quotients by Bergeron and Clozel [Quelques conséquences des travaux d’Arthur pour le spectre et la topologie des variétés hyperboliques,Invent. Math.192(2013), 505–532] and Venkataramana [Cohomology of compact locally symmetric spaces,Compos. Math.125(2001), 221–253]. The proofs combine techniques of mixed Hodge theory and methods involving automorphic forms.
Untilted edge slot antennas excited by T-shaped wires
Authors: Moradian Mahdi 
Published: October 2021

AbstractAn effective method is proposed to excite the untilted edge slot antennas. In the proposed method, two T-shaped wires are placed at both sides of each untilted slot. Two legs of each T-shaped wire are connected to the waveguide walls, while the third leg is open. One of the T-shaped wires connects the upper broad wall of the waveguide to the narrow wall of the waveguide which contains the slots. Similarly, the other T-shaped wires connect the lower broad wall of the waveguide to the narrow wall of the waveguide that contains the slots. The phase reversal between the adjacent slots can be accomplished by changing the orientation of the T-shaped wires. It is shown that the arm lengths of the connected wires can be employed as a parameter to control the radiated power by the slots. Furthermore, the arm lengths of the open wires can be selected properly to control the dynamic range of the equivalent normalized susceptance associated with each untilted slot antenna. To validate the effectiveness of the proposed antennas, two linear arrays consisting of 11 slots have been designed, implemented, and tested. The simulation and the measurement results of the designed arrays show that for the proposed untilted edge slot antennas, the dynamic range of the equivalent normalized susceptance is improved significantly which leads to a straightforward design process with no requirement to resort to any time-consuming tuning process.
Birthweight and subsequent risk for thyroid and autoimmune conditions in postmenopausal women
Authors: Monahan Brian , Farland Leslie V. , Shadyab Aladdin H. , Hankinson Susan E. , Manson JoAnn E. , Spracklen Cassandra N. 
Published: October 2021

AbstractThe objective of this study was to determine the association between birthweight and risk of thyroid and autoimmune conditions in a large sample of postmenopausal women. Baseline data from the Women’s Health Initiative (n = 80,806) were used to examine the associations between birthweight category (<6 lbs., 6–7 lbs. 15 oz, 8–9 lbs. 15 oz, and ≥10 lbs.) and prevalent thyroid (underactive and overactive thyroid and goiter) and autoimmune (lupus, rheumatoid arthritis (RA), multiple sclerosis, ulcerative colitis/Crohn’s disease) conditions. Follow-up questionnaire data were used to examine the associations between birthweight and incident underactive and overactive thyroid, lupus, and RA. Logistic and Cox proportional hazards regression models were used to estimate crude and adjusted odds (OR) and hazards ratios (HR), respectively. Overall, women born weighing ≥10 lbs. had an increased risk for underactive thyroid [OR 1.14 (95% CI 1.02, 1.28)] and incident lupus [HR 1.51 (95% CI 1.12, 2.03)] and a decreased risk for overactive thyroid [OR 0.67 (95% CI 0.50, 0.92)] compared to women born weighing 6–7.99 lbs., after adjustment for adult BMI, demographic variables, and lifestyle factors. Further, women born weighing <6 lbs. were at increased risk for underactive thyroid [OR 1.13 (95% CI 1.04, 1.22)]. Birthweight was not associated with other thyroid or autoimmune disorders. High birthweight was associated with later-life thyroid and autoimmune conditions while low birthweight was associated with underactive thyroid. Preconception and prenatal interventions aimed at reducing the risk of both high and low birthweights may reduce the burden of later-life thyroid and autoimmune conditions.
The androgen receptor—lncRNASAT1-AKT-p15 axis mediates androgen-induced cellular senescence in prostate cancer cells
Authors: Mirzakhani Kimia , Kallenbach Julia , Rasa Seyed Mohammad Mahdi , Ribaudo Federico , Ungelenk Martin , Ehsani Marzieh , Gong Wenrong , Gassler Nikolaus , Leeder Mirjam , Grimm Marc-Oliver , Neri Francesco , Baniahmad Aria 
Published: October 2021

AbstractThe bipolar androgen therapy (BAT) to treat prostate cancer (PCa) includes cycles of supraphysiological androgen levels (SAL) under androgen-deprivation therapy (ADT). We showed previously that SAL induces cellular senescence in androgen-sensitive PCa cells and in ex vivo-treated patient PCa tumor samples. Here, we analyzed the underlying molecular pathway and reveal that SAL induces cellular senescence in both, castration-sensitive (CSPC) LNCaP and castration-resistant PCa (CRPC) C4-2 cells through the cell cycle inhibitor p15INK4b and increased phosphorylation of AKT. Treatment with the AKT inhibitor (AKTi) potently inhibited SAL-induced expression of p15INK4b and cellular senescence in both cell lines. Proximity-ligation assays (PLA) combined with high-resolution laser-scanning microscopy indicate that SAL promotes interaction of endogenous androgen receptor (AR) with AKT in the cytoplasm as well as in the nucleus detectable after three days. Transcriptome sequencing (RNA-seq) comparing the SAL-induced transcriptomes of LNCaP with C4-2 cells as well as with AKTi-treated cell transcriptomes revealed landscapes for cell senescence. Interestingly, one of the identified genes is the lncRNASAT1. SAL treatment of native patient tumor samples ex vivo upregulates lncRNASAT1. In PCa tumor tissues, lncRNASAT1 is downregulated compared with nontumor tissues of the same patients. Knockdown indicates that the lncRNASAT1 is crucial for SAL-induced cancer-cell senescence as an upstream factor for pAKT and for p15INK4b. Further, knockdown of lncRNASAT1 enhances cell proliferation by SAL, suggesting that lncRNASAT1 serves as a tumor suppressor at SAL. Interestingly, immunoprecipitation of AR detected lncRNASAT1 as an AR-interacting partner that regulates AR target-gene expression. Similarly, RNA-ChIP experiments revealed the interaction of AR with lncRNASAT1 on chromatin. Thus, we identified a novel AR-lncRNASAT1-AKT-p15INK4b signaling axis to mediate SAL-induced cellular senescence.
Gene expression profiling in peripheral blood lymphocytes for major depression: preliminary cues from Chinese discordant sib-pair study
Authors: Wu Chan , Wang Danfeng , Niu Kangkang , Feng Qili , Chen Hanwei , Zhu Haibing , Xiang Hui 
Published: October 2021

AbstractThe etiology of major depressive disorder (MDD) involves many factors such as heredity and environment. There are very few MDD-related studies in Chinese population using twin or sib-pairs for depression-control samples. Here we used the microarray approach and compared gene expression profiling of peripheral blood lymphocytes from 6 sib-pairs discordant on lifetime history of MDD. Within sib-pair differentially expressed genes are obvious fewer in the 1st, 2nd, and 5th compared with those in the 3rd, 4th, and 6th sib-pairs. Gene expression pattern of these DEGs distinguished MDD individuals from the normal one in 3rd, 4th, and 6th sib-pair but not in the 1st, 2nd, and 5th pair, suggesting heterogeneity of different sib-pairs and somewhat commonalities among the 3rd, 4th, and 6th sib-pairs. Comprehensive protein interaction network analysis revealed two key genes PTH and FGF2 in a dominant network where the majority of the genes were significantly down-regulated. PTH was significantly down-regulated in all the sib-pairs while FGF2 was in the 3rd, 4th, and 6th sib-pairs. KEGG enrichment analysis of all the DEGs in networks showed that PTH and related genes were significantly enriched in the pathway of parathyroid hormone secretion, synthesis, and action while FGF2 and related genes were significantly enriched in the pathways of cancer and specifically breast cancer. Generally reduced expression of these genes in peripheral blood lymphocytes of MDD individuals implied their functional repression associated with MDD. Pending validation in more samples, the findings in this study provided valuable cues for understanding the potential mechanism of MDD, as well as potential markers for the diagnosis and treatment of depression in the Chinese population.
ERp29 forms a feedback regulation loop with microRNA-135a-5p and promotes progression of colorectal cancer
Authors: Huang Jiebin , Jing Mengxia , Chen Xixi , Gao Yuanqi , Hua Huiying , Pan Chun , Wu Jing , Wang Xinqiong , Chen Xuehua , Gao Yujing , Xu Chundi , Li Pu 
Published: October 2021

AbstractExpression of endoplasmic reticulum (ER) stress-associated genes is often dysregulated in cancer progression. ER protein 29 (ERp29) is abnormally expressed in many neoplasms and plays an important role in tumorigenesis. Here, we showed ERp29 is a novel target for microRNA-135a-5p (miR-135a-5p) to inhibit the progression of colorectal cancer (CRC); correspondingly, ERp29 acts as an oncoprotein in CRC by promoting proliferation and metastasis of CRC cells, and suppressing apoptosis of the cells. More importantly, we found that miR-135a-5p expression is reversely upregulated by ERp29 through suppressing IL-1β-elicited methylation of miR-135a-5p promoter region, a process for enterocyte to maintain a balance between miR-135a-5p and ERp29 but dysregulated in CRC. Our study reveals a novel feedback regulation loop between miR-135a-5p and ERp29 that is critical for maintaining appropriate level of each of them, but partially imbalanced in CRC, resulting in abnormal expression of miR-135a-5p and ERp29, which further accelerates CRC progression. We provide supporting evidence for ERp29 and miR-135a-5p as potential biomarkers for diagnosis and treatment of CRC.
Histone demethylase KDM4D inhibition suppresses renal cancer progression and angiogenesis through JAG1 signaling
Authors: Yan Hao , Zhu Liangsong , Zhang Jin , Lin Zongming 
Published: October 2021

AbstractKidney cancer, especially clear cell renal cell carcinoma (ccRCC), is one of the representative genitourinary tumors. Investigation of underlying mechanisms of ccRCC development is crucial for patient management. Histone demethylase KDM4D has been reported to be responsible for development of a variety of cancers. However, the role of KDM4D in ccRCC progression is poorly understood. In our study, we performed immunohistochemistry analysis of tissue microarrays first, and results showed that high expression level of KDM4D is connected with advanced Fuhrman grade (p = 0.0118) and lower overall survival (p = 0.0020). Then, we revealed that KDM4D can prompt ccRCC development by interacting with genes related to vessel morphogenesis. Finally, we disclosed that KDM4D directly interacts with JAG1 promoter and advances tumor angiogenesis by upregulating VEGFR-3 and antagonizing notch signaling. The results of our study indicate that KDM4D would be a potential prognostic marker and therapeutic target for ccRCC patients.
TM7SF2 regulates cell proliferation and apoptosis by activation of C-Raf/ERK pathway in cervical cancer
Authors: Xu Yichi , Chen Xin , Pan Shuya , Wang Zhi-wei , Zhu Xueqiong 
Published: October 2021

AbstractTransmembrane 7 superfamily member 2 (TM7SF2) coding an enzyme involved in cholesterol metabolism has been found to be differentially expressed in kinds of tissues. Nevertheless, the role of TM7SF2 in the regulation of growth and progression among various cancers is unclear. In this study, the immunohistochemistry (IHC) assay, real-time RT-PCR and western blotting analysis were used to determine the TM7SF2 expression in cervical cancer tissues. Next, we used multiple methods to determine the ability of cell proliferation, migration, invasion, apoptosis, and cell cycle in cervical cancer cells after TM7SF2 modulation, such as CCK8 assay, colony formation assay, Transwell assay, wound healing assay, and flow cytometry. Our results revealed that upregulation of TM7SF2 facilitated cell proliferation and metastasis, suppressed cell apoptosis and prevented G0/G1 phase arrests in C33A and SiHa cells. Consistently, the opposite effects were observed after TM7SF2 knockout in cervical cancer cells. Further, we found that TM7SF2 participated in promoting tumorigenesis and progression via activation of C-Raf/ERK pathway in cervical cancer, which can be partly reversed by Raf inhibitor LY3009120. Moreover, TM7SF2 overexpression contributed to enhancement of xenograft tumor growth in vivo. Our findings indicated that TM7SF2 plays a vital role in tumor promotion by involving in C-Raf/ERK activation. Therefore, TM7SF2 could serve as a therapeutic target in future cervical cancer treatment.
RCN1 induces sorafenib resistance and malignancy in hepatocellular carcinoma by activating c-MYC signaling via the IRE1α–XBP1s pathway
Authors: Wang Jia-Wei , Ma Li , Liang Yuan , Yang Xiao-Jun , Wei Song , Peng Hao , Qiu Shi-Pei , Lu Xu , Zhu Ya-Qing , Wang Bao-Lin 
Published: October 2021

AbstractThe increasing incidence of hepatocellular carcinoma (HCC) is of great concern globally, but the molecular pathogenesis of these tumors remains unclear. Sorafenib is a first-line drug for the treatment of advanced HCC. However, the efficacy of sorafenib in improving patient survival is limited, and most patients inevitably develop resistance to this drug. Recent studies have demonstrated that the activation of the IRE1α–XBP1s pathway might play a protective role in the response to sorafenib and contribute to malignancy in HCC. Here, we found that RCN1, an endoplasmic reticulum resident protein, is significantly upregulated in sorafenib-resistant HCC cells and promotes tumor progression. Our analysis showed that RCN1 may be an independent predictor of tumor recurrence and overall survival. Mechanistically, RCN1 promotes the dissociation of GRP78 from IRE1α in sorafenib-resistant cells by interacting with GRP78 through its EFh1/2 domain. Subsequently, the IRE1α–XBP1s pathway, a branch of the unfolded protein response, is sustainably activated. Interestingly, IRE1α–XBP1s pathway activity is required for c-MYC signaling, one of the most highly activated oncogenic pathways in HCC. These results suggest that RCN1-targeted therapy might be a feasible strategy for the treatment of HCC.
Oridonin inhibits DNMT3A R882 mutation-driven clonal hematopoiesis and leukemia by inducing apoptosis and necroptosis
Authors: Liao Min , Dong Qiongye , Chen Ruiqing , Xu Liqian , Jiang Yuxuan , Guo Zhenxing , Xiao Min , He Wei , Cao Changcai , Hu Ronghua , Sun Wanling , Jiang Hong , Wang Jianwei 
Published: October 2021

AbstractDNA (cytosine-5)-methyltransferase 3A (DNMT3A) mutations occur in ~20% of de novo acute myeloid leukemia (AML) patients, and >50% of these mutations in AML samples are heterozygous missense alterations within the methyltransferase domain at residue R882. DNMT3A R882 mutations in AML patients promote resistance to anthracycline chemotherapy and drive relapse. In this study, we performed high-throughput screening and identified that oridonin, an ent-kaurene diterpenoid extracted from the Chinese herb Rabdosia rubescens, inhibits DNMT3A R882 mutant leukemic cells at a low-micromolar concentration (IC50 = 2.1 µM) by activating both RIPK1-Caspase-8-Caspase-3-mediated apoptosis and RIPK1-RIPK3-MLKL-mediated necroptosis. The inhibitory effect of oridonin against DNMT3A R882 mutant leukemia cells can also be observed in vivo. Furthermore, oridonin inhibits clonal hematopoiesis of hematopoietic stem cells (HSCs) with Dnmt3a R878H mutation comparing to normal HSCs by inducing apoptosis and necroptosis. Overall, oridonin is a potential and promising drug candidate or lead compound targeting DNMT3A R882 mutation-driven clonal hematopoiesis and leukemia.
Fast ion transport for synthesis and stabilization of β-Zn4Sb3
Authors: Yang Dongwang , Su Xianli , He Jian , Yan Yonggao , Li Jun , Bai Hui , Luo Tingting , Liu Yamei , Luo Hao , Yu Yimeng , Wu Jinsong , Zhang Qingjie , Uher Ctirad , Tang Xinfeng 
Published: October 2021

AbstractMobile ion-enabled phenomena make β-Zn4Sb3 a promising material in terms of the re-entry phase instability behavior, mixed electronic ionic conduction, and thermoelectric performance. Here, we utilize the fast Zn2+ migration under a sawtooth waveform electric field and a dynamical growth of 3-dimensional ionic conduction network to achieve ultra-fast synthesis of β-Zn4Sb3. Moreover, the interplay between the mobile ions, electric field, and temperature field gives rise to exquisite core-shell crystalline-amorphous microstructures that self-adaptively stabilize β-Zn4Sb3. Doping Cd or Ge on the Zn site as steric hindrance further stabilizes β-Zn4Sb3 by restricting long-range Zn2+ migration and extends the operation temperature range of high thermoelectric performance. These results provide insight into the development of mixed-conduction thermoelectric materials, batteries, and other functional materials.
A dual-reporter system for investigating and optimizing protein translation and folding in E. coli
Authors: Zutz Ariane , Hamborg Louise , Pedersen Lasse Ebdrup , Kassem Maher M. , Papaleo Elena , Koza Anna , Herrgård Markus J. , Jensen Sheila Ingemann , Teilum Kaare , Lindorff-Larsen Kresten , Nielsen Alex Toftgaard 
Published: October 2021

AbstractStrategies for investigating and optimizing the expression and folding of proteins for biotechnological and pharmaceutical purposes are in high demand. Here, we describe a dual-reporter biosensor system that simultaneously assesses in vivo protein translation and protein folding, thereby enabling rapid screening of mutant libraries. We have validated the dual-reporter system on five different proteins and find an excellent correlation between reporter signals and the levels of protein expression and solubility of the proteins. We further demonstrate the applicability of the dual-reporter system as a screening assay for deep mutational scanning experiments. The system enables high throughput selection of protein variants with high expression levels and altered protein stability. Next generation sequencing analysis of the resulting libraries of protein variants show a good correlation between computationally predicted and experimentally determined protein stabilities. We furthermore show that the mutational experimental data obtained using this system may be useful for protein structure calculations.
De novo biosynthesis of bioactive isoflavonoids by engineered yeast cell factories
Authors: Liu Quanli , Liu Yi , Li Gang , Savolainen Otto , Chen Yun , Nielsen Jens 
Published: October 2021

AbstractIsoflavonoids comprise a class of plant natural products with great nutraceutical, pharmaceutical and agricultural significance. Their low abundance in nature and structural complexity however hampers access to these phytochemicals through traditional crop-based manufacturing or chemical synthesis. Microbial bioproduction therefore represents an attractive alternative. Here, we engineer the metabolism of Saccharomyces cerevisiae to become a platform for efficient production of daidzein, a core chemical scaffold for isoflavonoid biosynthesis, and demonstrate its application towards producing bioactive glucosides from glucose, following the screening-reconstruction-application engineering framework. First, we rebuild daidzein biosynthesis in yeast and its production is then improved by 94-fold through screening biosynthetic enzymes, identifying rate-limiting steps, implementing dynamic control, engineering substrate trafficking and fine-tuning competing metabolic processes. The optimized strain produces up to 85.4 mg L−1 of daidzein and introducing plant glycosyltransferases in this strain results in production of bioactive puerarin (72.8 mg L−1) and daidzin (73.2 mg L−1). Our work provides a promising step towards developing synthetic yeast cell factories for de novo biosynthesis of value-added isoflavonoids and the multi-phased framework may be extended to engineer pathways of complex natural products in other microbial hosts.
Transcriptome profiling of pepper leaves by RNA-Seq during an incompatible and a compatible pepper-tobamovirus interaction
Authors: Kalapos Balázs , Juhász Csilla , Balogh Eszter , Kocsy Gábor , Tóbiás István , Gullner Gábor 
Published: October 2021

AbstractUpon virus infections, the rapid and comprehensive transcriptional reprogramming in host plant cells is critical to ward off virus attack. To uncover genes and defense pathways that are associated with virus resistance, we carried out the transcriptome-wide Illumina RNA-Seq analysis of pepper leaves harboring the L3 resistance gene at 4, 8, 24 and 48 h post-inoculation (hpi) with two tobamoviruses. Obuda pepper virus (ObPV) inoculation led to hypersensitive reaction (incompatible interaction), while Pepper mild mottle virus (PMMoV) inoculation resulted in a systemic infection without visible symptoms (compatible interaction). ObPV induced robust changes in the pepper transcriptome, whereas PMMoV showed much weaker effects. ObPV markedly suppressed genes related to photosynthesis, carbon fixation and photorespiration. On the other hand, genes associated with energy producing pathways, immune receptors, signaling cascades, transcription factors, pathogenesis-related proteins, enzymes of terpenoid biosynthesis and ethylene metabolism as well as glutathione S-transferases were markedly activated by ObPV. Genes related to photosynthesis and carbon fixation were slightly suppressed also by PMMoV. However, PMMoV did not influence significantly the disease signaling and defense pathways. RNA-Seq results were validated by real-time qPCR for ten pepper genes. Our findings provide a deeper insight into defense mechanisms underlying tobamovirus resistance in pepper.