bluuebunny/crossref_metadata_2025_split huggingface dataset:
tRNA-derived fragments and microRNAs in the maternal-fetal interface of a mouse maternal-immune-activation autism model
Authors: Su Zhangli , Frost Elizabeth L. , Lammert Catherine R. , Przanowska Roza K. , Lukens John R. , Dutta Anindya 
Published: December 2019

AbstracttRNA-derived small fragments (tRFs) and tRNA halves have emerging functions in different biological pathways, such as regulating gene expression, protein translation, retrotransposon activity, transgenerational epigenetic changes and response to environmental stress. However, small RNAs like tRFs and microRNAs in the maternal-fetal interface during gestation have not been studied extensively. Here we investigated the small RNA composition of mouse placenta/decidua, which represents the interface where the mother communicates with the fetus, to determine whether there are specific differences in tRFs and microRNAs during fetal development and in response to maternal immune activation (MIA). Global tRF expression pattern, just like microRNAs, can distinguish tissue types among placenta/decidua, fetal brain and fetal liver. In particular, 5’ tRNA halves from tRNAGly, tRNAGlu, tRNAValand tRNALysare abundantly expressed in the normal mouse placenta/decidua. Moreover, tRF and microRNA levels in the maternal-fetal-interface change dynamically over the course of embryonic development. To see if stress alters non-coding RNA expression at the maternal-fetal interface, we treated pregnant mice with a viral infection mimetic, which has been shown to promote autism-related phenotypes in the offspring. Acute changes in the levels of specific tRFs and microRNAs were observed 3-6 hours after MIA and are suppressed thereafter. A group of 5’ tRNA halves is down-regulated by MIA, whereas a group of 18-nucleotide tRF-3a is up-regulated. In conclusion, tRFs show tissue-specificity, developmental changes and acute response to environmental stress, opening the possibility of them having a role in the fetal response to MIA.
Genetic erosion reduces biomass temporal stability in wild fish populations
Authors: Prunier Jérôme G. , Chevalier Mathieu , Raffard Allan , Loot Géraldine , Poulet Nicolas , Blanchet Simon 
Published: December 2019

ABSTRACTGenetic diversity sustains species adaptation. However, it may also support key ecosystems functions and services that can be altered by the worldwide loss of genetic diversity. Here, using long-term wild fish data, we demonstrate that populations with high genetic diversity do not reach higher biomasses than populations with low genetic diversity. Nonetheless, populations with high genetic diversity have much more stable biomasses over recent decades than populations having suffered from genetic erosion, which has implications for the provision of ecosystem services and the risk of population extinction. Our results strengthen the importance of adopting prominent environmental policies to conserve this important biodiversity facet.
Alzheimer’s disease-related dysregulation of protein synthesis causes key pathological features with ageing
Authors: Ghosh Anshua , Mizuno Keiko , Tiwari Sachin S. , Proitsi Petroula , Perez-Nievas Beatriz Gomez , Glennon Elizabeth , Martinez-Nunez Rocio T. , Peter Giese K. 
Published: December 2019

AbstractAlzheimer’s disease (AD) is characterised by Aβ and tau pathology as well as synaptic degeneration. Recently, it was suggested that the development of these key disease features may at least in part be due to increased protein synthesis that is regulated by fragile X mental retardation protein (FMRP) and its binding partner CYFIP2. Using an unbiased screen, we show that exposure of primary neurons to Aβ increases FMRP-regulated protein synthesis and involves a reduction of CYFIP2 levels. Modelling this CYFIP2 reduction in mice, we find Aβ accumulation, development of pre-tangle tau pathology, gliosis, loss of synapses, and deficits in memory formation with ageing. We conclude that reducing endogenous CYFIP2 expression is sufficient to cause some key features of AD in mice. We therefore propose a central role for CYFIP2 in AD as a modulator of protein synthesis, highlighting a novel direction for therapeutic targeting.
Identifying Core Operons in Metagenomic Data
Authors: Hu Xiao , Friedberg Iddo 
Published: December 2019

AbstractAn operon is a functional unit of DNA whose genes are co-transcribed on polycistronic mRNA, in a co-regulated fashion. Operons are a powerful mechanism of introducing functional complexity in bacteria, and are therefore of interest in microbial genetics, physiology, biochemistry, and evolution. Here we present a Pipeline for Operon Exploration in Metagenomes or POEM. At the heart of POEM lies the concept of a core operon, a functional unit enabled by a predicted operon in a metagenome. Using a series of benchmarks, we show the high accuracy of POEM, and demonstrate its use on a human gut metagenome sample. We conclude that POEM is a useful tool for analyzing metagenomes beyond the genomic level, and for identifying multi-gene functionalities and possible neofunctionalization in metagenomes. Availability:https://github.com/Rinoahu/POEM_py3k
The protective effect of club cell secretory protein (CC-16) on COPD risk and progression: a Mendelian randomisation study
Authors: Milne Stephen , Li Xuan , Cordero Ana I Hernandez , Yang Chen Xi , Cho Michael H , Beaty Terri H , Ruczinski Ingo , Hansel Nadia N , Bossé Yohan , Brandsma Corry-Anke , Sin Don D , Obeidat Ma’en 
Published: December 2019

ABSTRACTBackgroundThere are currently no robust biomarkers of chronic obstructive pulmonary disease (COPD) risk or progression. Club cell secretory protein-16 (CC-16) is associated with the clinical expression of COPD. We aimed to determine if there is a causal effect of serum CC-16 level on COPD risk and/or progression using Mendelian randomisation (MR) analysis.MethodsWe performed a genome-wide association meta-analysis for serum CC-16 in two COPD cohorts (Lung Health Study [LHS], n=3,850 and ECLIPSE, n=1,702). We then used the CC-16-associated single-nucleotide polymorphisms (SNPs) in MR analysis to estimate the causal effect of serum CC-16 on COPD risk (International COPD Genetics Consortium/UK-Biobank dataset; n=35,735 cases, n=222,076 controls) and progression (change in forced expiratory volume in 1 s [FEV1] in LHS and ECLIPSE). We also determined the associations between SNPs associated with CC-16 and gene expression using n=1,111 lung tissue samples from the Lung eQTL Study.ResultsWe identified 7 SNPs independently associated (p<5×10−8) with serum CC-16 levels; 6 of these were novel. MR analysis suggested a protective causal effect of increased serum CC-16 on COPD risk (p=0.008) and progression (LHS only, p=0.02). Five of the SNPs were also associated with gene expression in lung tissue, including that of the CC-16-encoding geneSCGB1A1(false discovery rate<0.1).ConclusionWe have identified several novel genetic variants associated with serum CC-16 level in COPD cohorts. These genetic associations suggest a potential causal effect of serum CC-16 on COPD risk and progression. Further investigation of CC-16 as a biomarker or therapeutic target in COPD is warranted.KEY MESSAGESWhat is the key question?Can genetics help uncover a causal effect of serum CC-16 level on COPD risk and/or progression?What is the bottom line?There is a protective effect of genetically-increased serum CC-16 on both COPD risk and progression (as measured by change in FEV1over time), which may be due to increased expression of the CC-16-encoding geneSCGB1A1in the lung.Why read on?This is the first study to demonstrate a possible causal effect of serum CC-16 in people with COPD, and highlights the potential for CC-16 as a biomarker or therapeutic target.
Optimal maturation of the SIV-specific CD8+T-cell response after primary infection is associated with natural control of SIV. ANRS SIC study
Authors: Passaes Caroline , Millet Antoine , Madelain Vincent , Monceaux Valérie , David Annie , Versmisse Pierre , Sylla Naya , Gostick Emma , Price David A. , Blancher Antoine , Dereuddre-Bosquet Nathalie , Pancino Gianfranco , Grand Roger Le , Lambotte Olivier , Müller-Trutwin Michaela , Rouzioux Christine , Guedj Jeremie , Avettand-Fenoel Veronique , Vaslin Bruno , Sáez-Cirión Asier 
Published: December 2019

ABSTRACTHighly efficient virus-specific CD8+T-cells are associated with immune control of HIV infection, but it remains unclear how these cells are generated and maintained over time. We used a macaque model of spontaneous control of SIVmac251 infection to monitor the development and evolution of potent antiviral CD8+T-cell responses. SIV-specific CD8+T-cells emerged during primary infection in all animals. However, the ability of CD8+T cells to suppress SIV replication was low in early stages but increased after a period of maturation, temporally linked with the establishment of sustained low-level viremia in controller macaques. SIV-specific CD8+T-cells with a central memory phenotype expressed higher levels of survival markers in controllersversusnon-controllers. In contrast, a persistently skewed differentiation phenotype was observed among central memory SIV-specific CD8+T-cells in non-controllers since primary infection, typified by relatively high expression levels of T-bet.Collectively, these data show that the phenotype of SIV-specific CD8+T-cells defined early after SIV infection favor the gain of antiviral potency as a function of time in controllers, whereas SIV-specific CD8+T-cell responses in non-controllers fail to gain antiviral potency due to early defects imprinted in the central memory pool.
Chlorotoxin Conjugated with Saporin Reduces Viability of ML-1 Thyroid Cancer Cells In Vitro
Authors: Rizvanovic Husref , Pinheiro A Daniel , Kim Kyoungtae , Thomas Johnson 
Published: December 2019

AbstractBackgroundAlthough differentiated thyroid cancer has good prognosis, radioactive iodine (RAI) resistant thyroid cancer is difficult to treat. Current therapies for progressive RAI resistant thyroid cancer are not very effective. There is an unmet need for better therapeutic agents in this scenario. Studies have shown that aggressive thyroid cancers express matrix metalloproteinase −2 (MMP-2). Chlorotoxin is a selective MMP-2 agonist. Given that Saporin is a well-known ribosome-inactivating protein used for anti-cancer treatment, we hypothesized that Chlorotoxin-conjugated Saporin (CTX-SAP) would inhibit the growth of aggressive thyroid cancer cell lines expressing MMP-2.MethodsThe ML-1 thyroid cancer cell line was used for this study because it is known to express MMP-2. ML-1 cells were treated with a toxin consisting of biotinylated Chlorotoxin bonded with a secondary conjugate of Streptavidin-ZAP containing Saporin (CTX-SAP) from 0 to 600 nM for 72 hours. Then, cell viability was measured via XTT assay at an absorbance of A450-630. Control experiments were set up using Chlorotoxin and Saporin individually at the same varying concentrations.ResultsAfter 7 hours of incubation, there was a statistically significant reduction in cell viability with increasing concentrations of the CTX-SAP conjugate (F=4.286, p=0.0057). In particular, the cell viability of ML-1 cells was decreased by 49.77% with the treatment of 600 nM of CTX-SAP (F=44.24), and the reduction in cell viability was statistically significant (Dunnett’s test p<0.0001). In contrast, individual Chlorotoxin or Saporin in increasing concentrations had no significant effect on cell viability using similar assay.ConclusionThisin vitrostudy demonstrated the efficacy of a CTX-SAP conjugate in reducing the viability of ML-1 thyroid cancer cells in a dose dependent manner. Further studies are needed to delineate the effectiveness of CTX-SAP in the treatment of aggressive thyroid cancer. Our study points towards MMP-2 as a potential target for RAI-resistant thyroid cancer.
Micrografting device for testing environmental conditions for grafting and systemic signaling in Arabidopsis
Authors: Tsutsui Hiroki , Yanagisawa Naoki , Kawakatsu Yaichi , Ikematsu Shuka , Sawai Yu , Tabata Ryo , Arata Hideyuki , Higashiyama Tetsuya , Notaguchi Michitaka 
Published: December 2019

SummaryGrafting techniques have been applied in studies of systemic, long-distance signaling in several model plants. Seedling grafting in Arabidopsis, known as micrografting, enables investigation of the molecular mechanisms of systemic signaling between shoots and roots. However, conventional micrografting requires a high level of skill, limiting its use. Thus, an easier user-friendly method is needed. Here, we developed a silicone microscaled device, the micrografting chip, to obviate the need for training and to generate less stressed and more uniformly grafted seedlings. The chip has tandemly arrayed units, each of which consists of a seed pocket for seed germination and a micro-path with pairs of pillars for hypocotyl holding. Grafting, including seed germination, micrografting manipulation, and establishment of tissue reunion, is performed on the chip. Using the micrografting chip, we evaluated the effect of temperature and the carbon source on grafting and showed that a temperature of 27°C and a sucrose concentration of 0.5% were optimal. We also used the chip to investigate the mechanism of systemic signaling of iron status using a quadruple nicotianamine synthase (nas) mutant. The constitutive iron-deficiency response in thenasmutant because of aberrant partitioning was significantly rescued by grafting of wild-type shoots or roots, suggesting that shoot-and root-ward translocation of nicotianamine–iron complexes is essential for iron mobilization. Thus, our micrografting chip will promote studies of long-distance signaling in plants.Significance StatementA number of micrografting studies on systemic, long-distance signaling have been performed, but the technique is not yet used widely. Here, we developed a silicone-based micrografting chip to improve the ease-of-use, efficiency, and success rate of micrografting, even for untrained users.
Log Transformation Improves Dating of Phylogenies
Authors: Mai Uyen , Mirarab Siavash 
Published: December 2019

AbstractPhylogenetic trees inferred from sequence data often have branch lengths measured in the expected number of substitutions and therefore, do not have divergence times estimated. These trees give an incomplete view of evolutionary histories since many applications of phylogenies require time trees. Many methods have been developed to convert the inferred branch lengths from substitution unit to time unit using calibration points, but none is universally accepted as they are challenged in both scalability and accuracy under complex models. Here, we introduce a new method that formulates dating as a non-convex optimization problem where the variance of log-transformed rate multipliers are minimized across the tree. On simulated and real data, we show that our method, wLogDate, is often more accurate than alternatives and is more robust to various model assumptions.
Risk of preterm birth in a twin pregnancy after an early‐term birth in the preceding singleton pregnancy: a retrospective cohort study
Authors: Berveiller P , Rousseau A , Rousseau M , Bitumba I , Goffinet F , Rozenberg P 
Published: December 2019

ObjectiveTo evaluate whether a history of spontaneous early‐term birth (37+0–38+6 weeks of gestation) in the previous singleton pregnancy is a risk factor for preterm birth (PTB) in a subsequent twin pregnancy.DesignRetrospective cohort study.SettingsTwo French university hospitals (2006–2016).PopulationAll women who delivered twins from 24+0 weeks after a preceding singleton pregnancy birth at 37+0 to 41+6 weeks.MethodsMultivariate logistic regression analysis of association between twin PTB and a previous spontaneous singleton early‐term birth.Main outcome measuresTwin PTB rate before 37, 34 and 32 weeks of gestation.ResultsAmong 618 twin pregnancies, 270 were born preterm, 92 of them with a preceding spontaneous singleton early‐term birth. The univariate analysis showed a significantly higher risk of twin PTB before 37, 34 and 32 weeks among those 92 women compared with those with a full‐ or late‐term birth in their previous singleton pregnancy. This association remained significant after logistic regression (odds ratio [OR] between 2.42 and 3.88). The secondary analysis, restricted to the twin pregnancies with spontaneous PTB found similar results, with a risk of PTB before 37, 34 and 32 weeks significantly higher among women with a previous spontaneous singleton early‐term birth, including after logistic regression analysis (OR between 3.51 and 3.56).ConclusionA preceding spontaneous singleton early‐term birth is a strong and easily identified risk factor for PTB in twin pregnancies.Tweetable abstractSpontaneous ‘early‐term’ birth of a singleton is a significant risk factor for future preterm births in twin pregnancies.
Renal transplantation in HLA sensitized patients: Traversing the immunological barrier
Authors: Pandey Prashant , Setya Divya , Sinha Vijay , Bhatt Anil , Devra Amit , Pande Amit , Kumar Praveen , Ranjan Shweta 
Published: December 2019

AbstractSuccessful renal transplantation across HLA barrier in sensitized individuals has been on the rise during the past decade, primarily due to improved desensitization regimes. The aim of this study was to share outcome of desensitization in renal transplant recipients with donor‐specific anti‐HLA antibodies (DSA). This was a retrospective analysis of all HLA immunized individuals who were prospective renal transplant recipients. All such patients underwent preconditioning as per the institutional desensitization protocol. Complement‐dependent cytoxicity‐based crossmatch (CDC‐XM), luminex‐based crossmatch (LM‐XM) and flowcytometry‐based crossmatch (FC‐XM) were done in all cases. If any of these tests turned out positive, single antigen bead assay (SAB) was performed. Desensitization for DSA was performed in 55 patients and all patients were followed‐up for 1 year to assess graft function and patient outcome. CDC‐XM being a less sensitive assay, could not detect incompatibility in 29 (52.73%) cases. After desensitization, even though SAB and LM‐XM results revealed an MFI within acceptable range, FC‐XM being an extremely sensitive assay, continued to give a positive result in eight (14.55%) cases. The mean ± SD number of pretransplant TPE were 3.44 ± 0.98 (2‐11). Out of 55, there were 10 patients who were lost to follow up. Patient and graft survival of 45 patients at 1 year was found to be 100%. Preconditioning for renal transplants in the form of immunosuppression with TPE is an extremely useful auxiliary for transplantation in HLA sensitized renal transplant recipients.
Quantitative analysis for modified Schall's classification by stimulation test with dynamic scintigraphy in Sjögren's syndrome
Authors: Zhu Guang‐wen , Gao Zhou , Feng Hong‐bo , Qiu Juan‐juan 
Published: December 2019

AbstractObjectivesTo update Schall's classification for Sjögren's syndrome (SS) by the new quantitative stimulation test with dynamic salivary glands scintigraphy (qsDSGS) and to standardize quantitative salivary gland scintigraphy.MethodsThe histopathology, oral, ocular, serological examination and qsDSGS of 268 consecutive patients with suggestive SS were evaluated in this retrospective cohort study. The serological examination included 15 autoantibodies, antinuclear antibodies (ANA) and so on. The diagnostic thresholds of the functional parameters were set by the quantitative method, and the modified Schall's classification is well established and verified.ResultsBased on the quantitative analysis of qsDSGS, the peak uptake level (PUL) and stimulation excretion fraction (sEF) of each parotid gland were determined as the key imaging features, which had good diagnostic performance for SS. By the modified Schall's classification, all patients were classified into: Class 1 (normal; n = 44), Class 2 (mild to moderate involvement; n = 130), Class 3 (severe involvement; n = 56) and Class 4 (very severe involvement, non‐function; n = 38). Using the threshold PUL ≤ 10 counts per sec/pixel as positivity, the modified Schall's classification could provide better diagnostic performance with 88.4% specificity, 71.3% sensitivity, 96.14% positive predictive value and 43.20% negative predictive value for SS (likelihood ratio 6.15). The trends of serologically positive frequencies against SSA/Ro, anti‐SSB/La and ANA were significantly increased with the new classification.ConclusionThe modified Schall's classification by the new stimulation test with dynamic scintigraphy is eligible to standardize quantitative salivary gland scintigraphy for SS, and may be more convenient and suitable in daily practice for clinical research and management of SS.
Alleviating the Thucydides' Trap through Welfare State Dependence: How the Funding Needs of the Western Welfare State Can Influence Multilateral Relations with China
Authors: Avgouleas Emilios , Trigkas Vasilis 
Published: December 2019

AbstractThe dual threat of a US–China confrontation and the rise of populism in the West due, in part, to the gradual decay of the welfare state, paint an ominous picture for the future of the post‐war status quo of ever‐expanding prosperity. Hegemonic competition between the incumbent superpower (the USA) and the challenger (China) framed as the Thucydides' Trap and adverse demographic and financial trends are the main causes behind both crises. In this paper, we argue that amidst deteriorating demographics, the sustainability of the Western welfare state could be significantly enhanced by positioning Western institutional investments in the regions across India and South East Asia – areas with strong modernization dynamics and the world's nascent most populous middle class. Such a policy could generate long‐term higher risk‐adjusted returns for Western pension funds, especially if Western investors look for complementarities with China's Belt and Road Initiative (BRI). The proposed geographical calibration in Western institutional investments could lead to a relationship of strong reciprocal dependence between economic and social growth in the target regions, exports of Chinese construction and financial capacity, and Western welfare state viability. We call the suggested policy the ‘welfare state dependence’ hypothesis. The key objective of the hypothesis is the promotion of peaceful economic and geopolitical co‐existence in Eurasia through rational re‐alignment of the incentives of Western polities with Eurasian growth. But to make this new approach feasible, a number of BRI policy reforms that support its multilateralization are required.