bluuebunny/crossref_metadata_2025_split huggingface dataset:
Giant tortoise genomes provide insights into longevity and age-related disease
Authors: Quesada Víctor , Freitas-Rodríguez Sandra , Miller Joshua , Pérez-Silva José G. , Jiang Zi-Feng , Tapia Washington , Santiago-Fernández Olaya , Campos-Iglesias Diana , Kuderna Lukas F. K. , Quinzin Maud , Álvarez Miguel G. , Carrero Dido , Beheregaray Luciano B. , Gibbs James P. , Chiari Ylenia , Glaberman Scott , Ciofi Claudio , Araujo-Voces Miguel , Mayoral Pablo , Arango Javier R. , Tamargo-Gómez Isaac , Roiz-Valle David , Pascual-Torner María , Evans Benjamin R. , Edwards Danielle L. , Garrick Ryan C. , Russello Michael A. , Poulakakis Nikos , Gaughran Stephen J. , Rueda Danny O. , Bretones Gabriel , Marquès-Bonet Tomàs , White Kevin P. , Caccone Adalgisa , López-Otín Carlos 
Published: November 2018

AbstractGiant tortoises are among the longest-lived vertebrate animals and, as such, provide an excellent model to study traits like longevity and age-related diseases. However, genomic and molecular evolutionary information on giant tortoises is scarce. Here, we describe a global analysis of the genomes of Lonesome George—the iconic last member of Chelonoidis abingdonii—and the Aldabra giant tortoise (Aldabrachelys gigantea). Comparison of these genomes with those of related species, using both unsupervised and supervised analyses, led us to detect lineage-specific variants affecting DNA repair genes, inflammatory mediators and genes related to cancer development. Our study also hints at specific evolutionary strategies linked to increased lifespan, and expands our understanding of the genomic determinants of ageing. These new genome sequences also provide important resources to help the efforts for restoration of giant tortoise populations.
Micro-RNAs, their target proteins, predispositions and the memory of filial imprinting
Authors: Margvelani Giorgi , Meparishvili Maia , Kiguradze Tamar , McCabe Brian J. , Solomonia Revaz 
Published: November 2018

AbstractVisual imprinting is a learning process whereby young animals come to prefer a visual stimulus after exposure to it (training). The intermediate medial mesopallium (IMM) in the domestic chick forebrain is critical for visual imprinting and contributes to molecular regulation of memory formation. We investigated the role of micro-RNAs (miRNAs) in such regulation. Twenty-four hours after training, miRNA spectra in the left IMM were compared between chicks with high preference scores (strong memory for imprinting stimulus), and chicks with low preference scores (weak memory for imprinting stimulus). Using criteria of significance and expression level, we chose gga-miR-130b-3p for further study and found that down-regulation correlated with learning strength. No effect was detected in posterior nidopallium, a region not involved in imprinting. We studied two targets of gga-miR-130b-3p, cytoplasmic polyadenylation element binding proteins 1 (CPEB-1) and 3 (CPEB-3), in two subcellular fractions (P2 membrane-mitochondrial and cytoplasmic) of IMM and posterior nidopallium. Only in the left IMM was a learning-related effect observed, in membrane CPEB-3. Variances from the regression with preference score and untrained chicks suggest that, in the IMM, gga-miR-130b-3p level reflects a predisposition, i.e. capacity to learn, whereas P2 membrane-mitochondrial CPEB-3 is up-regulated in a learning-specific way.
Evidence for Cognitive Placebo and Nocebo Effects in Healthy Individuals
Authors: Turi Zsolt , Bjørkedal Espen , Gunkel Luisa , Antal Andrea , Paulus Walter , Mittner Matthias 
Published: November 2018

AbstractInactive interventions can have significant effects on cognitive performance. Understanding the generation of these cognitive placebo/nocebo effects is crucial for evaluating the cognitive impacts of interventional methods, such as non-invasive brain stimulation (NIBS). We report both cognitive placebo and nocebo effects on reward-based learning performance induced using an active sham NIBS protocol, verbal suggestions and conditioning in 80 healthy participants. Whereas our placebo manipulation increased both expected and perceived cognitive performance, nocebo had a detrimental effect on both. Model-based analysis suggests manipulation-specific strategic adjustments in learning-rates: Participants in the placebo group showed stronger learning from losses and reduced behavioral noise, participants in the nocebo group showed stronger learning from gains and increased behavioral noise. We conclude that experimentally induced expectancy can impact cognitive functions of healthy adult participants. This has important implications for the use of double-blind study designs that can effectively maintain blinding in NIBS studies.
Stable isotopic evidence of nitrogen sources and C4 metabolism driving the world’s largest macroalgal green tides in the Yellow Sea
Authors: Valiela Ivan , Liu Dongyan , Lloret Javier , Chenoweth Kelsey , Hanacek Daniella 
Published: November 2018

AbstractDuring recent years, rapid seasonal growth of macroalgae covered extensive areas within the Yellow Sea, developing the world’s most spatially extensive “green tide”. The remarkably fast accumulation of macroalgal biomass is the joint result of high nitrogen supplies in Yellow Sea waters, plus ability of the macroalgae to optionally use C4 photosynthetic pathways that facilitate rapid growth. Stable isotopic evidence shows that the high nitrogen supply is derived from anthropogenic sources, conveyed from watersheds via river discharges, and by direct atmospheric deposition. Wastewater and manures supply about half the nitrogen used by the macroalgae, fertiliser and atmospheric deposition each furnish about a quarter of the nitrogen in macroalgae. The massive green tides affecting the Yellow Sea are likely to increase, with significant current and future environmental and human consequences. Addressing these changing trajectories will demand concerted investment in new basic and applied research as the basis for developing management policies.
Temporal and spatial patterns of mitochondrial haplotype and species distributions in Siberian larches inferred from ancient environmental DNA and modeling
Authors: Epp Laura S. , Kruse Stefan , Kath Nadja J. , Stoof-Leichsenring Kathleen R. , Tiedemann Ralph , Pestryakova Luidmila A. , Herzschuh Ulrike 
Published: November 2018

AbstractChanges in species’ distributions are classically projected based on their climate envelopes. For Siberian forests, which have a tremendous significance for vegetation-climate feedbacks, this implies future shifts of each of the forest-forming larch (Larix) species to the north-east. However, in addition to abiotic factors, reliable projections must assess the role of historical biogeography and biotic interactions. Here, we use sedimentary ancient DNA and individual-based modelling to investigate the distribution of larch species and mitochondrial haplotypes through space and time across the treeline ecotone on the southern Taymyr peninsula, which at the same time presents a boundary area of two larch species. We find spatial and temporal patterns, which suggest that forest density is the most influential driver determining the precise distribution of species and mitochondrial haplotypes. This suggests a strong influence of competition on the species’ range shifts. These findings imply possible climate change outcomes that are directly opposed to projections based purely on climate envelopes. Investigations of such fine-scale processes of biodiversity change through time are possible using paleoenvironmental DNA, which is available much more readily than visible fossils and can provide information at a level of resolution that is not reached in classical palaeoecology.
Structural insight into D-xylose utilization by xylose reductase from Scheffersomyces stipitis
Authors: Son Hyeoncheol Francis , Lee Sun-Mi , Kim Kyung-Jin 
Published: November 2018

AbstractLignocellulosic biomass, of which D-xylose accounts for approximately 35% of the total sugar, has attracted attention as a future energy source for biofuel. To elucidate molecular mechanism of D-xylose utilization, we determined the crystal structure of D-xylose reductase from Schefferzomyces stipitis (SsXR) at a 1.95 Å resolution. We also determined the SsXR structure in complex with the NADPH cofactor and revealed that the protein undergoes an open/closed conformation change upon NADPH binding. The substrate binding pocket of SsXR is somewhat hydrophobic, which seems to result in low binding affinity to the substrate. Phylogenetic tree analysis showed that AKR enzymes annotated with bacterial/archaeal XRs belonged to uncharacterized AKR families and might have no XR function, and yeast/fungi derived enzymes, which belong to the same group with SsXR, can be candidates for XR to increase xylose consumption.
Dynamic interaction of poly(A)-binding protein with the ribosome
Authors: Machida Kodai , Shigeta Tomoaki , Yamamoto Yuki , Ito Takuhiro , Svitkin Yuri , Sonenberg Nahum , Imataka Hiroaki 
Published: November 2018

AbstractEukaryotic mRNA has a cap structure and a poly(A) tail at the 5′ and 3′ ends, respectively. The cap structure is recognized by eIF (eukaryotic translation initiation factor) 4 F, while the poly(A) tail is bound by poly(A)-binding protein (PABP). PABP has four RNA recognition motifs (RRM1–4), and RRM1-2 binds both the poly(A) tail and eIF4G component of eIF4F, resulting in enhancement of translation. Here, we show that PABP interacts with the 40S and 60S ribosomal subunits dynamically via RRM2-3 or RRM3-4. Using a reconstituted protein expression system, we demonstrate that wild-type PABP activates translation in a dose-dependent manner, while a PABP mutant that binds poly(A) RNA and eIF4G, but not the ribosome, fails to do so. From these results, functional significance of the interaction of PABP with the ribosome is discussed.
A gB/CD3 bispecific BiTE antibody construct for targeting Human Cytomegalovirus-infected cells
Authors: Brey Charlotte U. , Proff Julia , Teufert Natascha , Salzer Benjamin , Brozy Johannes , Münz Markus , Pendzialek Jochen , Ensser Armin , Holter Wolfgang , Lehner Manfred 
Published: November 2018

AbstractBispecific T cell engager (BiTE) antibody constructs are successfully used as cancer therapeutics. We hypothesized that this treatment strategy could also be applicable for therapy of human cytomegalovirus (HCMV) infection, since HCMV-encoded proteins are abundantly expressed on the surface of infected cells. Here we show that a BiTE antibody construct directed against HCMV glycoprotein B (gB) and CD3 efficiently triggers T cells to secrete IFN-γ and TNF upon co-culture with fibroblasts infected with HCMV strain AD169, Towne or Toledo. Titration of gB expression levels in non-infected cells confirmed that already low levels of gB are sufficient for efficient triggering of T cells in presence of the BiTE antibody construct. Comparison of redirecting T cells with the bispecific antibody versus a chimeric antigen receptor (CAR) based on the same scFv showed a similar sensitivity for gB expression. Although lysis of infected target cells was absent, the BiTE antibody construct inhibited HCMV replication by triggering cytokine production. Notably, even strongly diluted supernatants of the activated T cells efficiently blocked the replication of HCMV in infected primary fibroblasts. In summary, our data prove the functionality of the first BiTE antibody construct targeting an HCMV-encoded glycoprotein for inhibiting HCMV replication in infected cells.
Golgi stress mediates redox imbalance and ferroptosis in human cells
Authors: Alborzinia Hamed , Ignashkova Tatiana I. , Dejure Francesca R. , Gendarme Mathieu , Theobald Jannick , Wölfl Stefan , Lindemann Ralph K. , Reiling Jan H. 
Published: November 2018

AbstractCytotoxic activities of several Golgi-dispersing compounds including AMF-26/M-COPA, brefeldin A and golgicide A have previously been shown to induce autophagy or apoptosis. Here, we demonstrate that these Golgi disruptors also trigger ferroptosis, a non-apoptotic form of cell death characterized by iron-dependent oxidative degradation of lipids. Inhibitors of ferroptosis not only counteract cell death, but they also protect from Golgi dispersal and inhibition of protein secretion in response to several Golgi stress agents. Furthermore, the application of sublethal doses of ferroptosis-inducers such as erastin and sorafenib, low cystine growth conditions, or genetic knockdown of SLC7A11 and GPX4 all similarly protect cells from Golgi stress and lead to modulation of ACSL4, SLC7A5, SLC7A11 or GPX4 levels. Collectively, this study suggests a previously unrecognized function of the Golgi apparatus, which involves cellular redox control and prevents ferroptotic cell death.
RollFISH achieves robust quantification of single-molecule RNA biomarkers in paraffin-embedded tumor tissue samples
Authors: Wu Chenglin , Simonetti Michele , Rossell Carla , Mignardi Marco , Mirzazadeh Reza , Annaratone Laura , Marchiò Caterina , Sapino Anna , Bienko Magda , Crosetto Nicola , Nilsson Mats 
Published: November 2018

AbstractSingle-molecule RNA fluorescence in situ hybridization (smFISH) represents a promising approach to quantify the expression of clinically useful biomarkers in tumor samples. However, routine application of smFISH to formalin-fixed, paraffin-embedded (FFPE) samples is challenging due to the low signal intensity and high background noise. Here we present RollFISH, a method combining the specificity of smFISH with the signal boosting of rolling circle amplification. We apply RollFISH to quantify widely used breast cancer biomarkers in cell lines and FFPE samples. Thanks to the high signal-to-noise ratio, we can visualize selected biomarkers at low magnification (20 × ) across entire tissue sections, and thus assess their spatial heterogeneity. Lastly, we apply RollFISH to quantify HER2 mRNA in 150 samples on a single tissue microarray, achieving a sensitivity and specificity of detection of HER2-positive samples of ~90%. RollFISH is a robust method for quantifying the expression and intratumor heterogeneity of biomarkers in FFPE tissues.
A tunable lanthanide cubane platform incorporating air-stable radical ligands for enhanced magnetic communication
Authors: Brunet Gabriel , Hamwi Milad , Lemes Maykon A. , Gabidullin Bulat , Murugesu Muralee 
Published: November 2018

AbstractThe unique properties of polynuclear cluster-aggregates have long been staples in the molecular magnetism community. The initial success observed in high nuclearity transition metal complexes for generating exciting magnetic behaviors however, has not yet fully been extended to lanthanide-based clusters. This is in part due to the challenges related to promoting non-negligible magnetic interactions between two lanthanide ions. One promising route towards improving magnetic communication involves the incorporation of radical species. Here, we describe the preparation of tetranuclear [Dy4(μ3-OH)4]8+ core structures that allow the incorporation of air-stable radical ligands. This combination paves the way for magnetically relevant lanthanide cubane cluster-aggregates capable of strong magnetic communication and improved spin-reversal barriers. Moreover, we show that the addition of electron donating groups lead to non-negligible antiferromagnetic coupling between the DyIII centers and the BPyTz•− ligands, while also simultaneously improving the slow magnetic relaxation dynamics in the absence of an applied field.
Total flavonoids extracted from Nervilia Fordii function in polycystic ovary syndrome through IL-6 mediated JAK2/STAT3 signaling pathway
Authors: Zhou Yanyuan , Lv Liang , Liu Qinghua , Song Jiale 
Published: November 2018

Abstract
Large doses of flavonoids could cure many diseases with no serious side effects. However, the role of flavonoids in the treatment of polycystic ovary syndrome (PCOS) has not been reported. Therefore, total flavonoids extracted from Nervilia Fordii were selected to explore its therapeutic efficiency in PCOS. PCOS rat model was constructed to explore the role of total flavonoids in the treatment of PCOS. ELISA was used to assess the changes of ovulation function under the treatment of total flavonoids with or without exogenous interleukin-6 (IL-6). Western blot, real-time PCR and immunohistochemistry were carried out to assess the related molecular mechanisms. We explored that total flavonoids obviously increased the serum levels of follicle-stimulating hormone (FSH), and sharply decreased the serum levels of luteinizing hormone (LH), testosterone (T) and insulin (INS) in the PCOS-IR rats via partly inhibiting the activation of JAK2/STAT3 pathway, partially up-regulating the IL-6 expression and partially down-regulating the suppressor of cytokine signaling 3 (SOCS3) expression in ovaries of PCOS rats. The effect of total flavonoids on estrous cycles, serum levels of FSH, LH, T and INS were partially attenuated by IL-6 in PCOS rat model. Moreover, IL-6 significantly reversed the effect of total flavonoids on the phosphorylation of JAK2/STAT3, the expression of IL-6 and SOCS3 in ovaries of PCOS rats. Total flavonoids extracted from Nervilia Fordii might induce the expression of IL-6 in ovary and act as a potential therapeutic drug for the treatment of PCOS.
The GAPS Programme with HARPS-N at TNG
Authors: Barbato D. , Sozzetti A. , Biazzo K. , Malavolta L. , Santos N. C. , Damasso M. , Lanza A. F. , Pinamonti M. , Affer L. , Benatti S. , Bignamini A. , Bonomo A. S. , Borsa F. , Carleo I. , Claudi R. , Cosentino R. , Covino E. , Desidera S. , Esposito M. , Giacobbe P. , González-Álvarez E. , Gratton R. , Harutyunyan A. , Leto G. , Maggio A. , Maldonado J. , Mancini L. , Masiero S. , Micela G. , Molinari E. , Nascimbeni V. , Pagano I. , Piotto G. , Poretti E. , Rainer M. , Scandariato G. , Smareglia R. , Colombo L. S. , Di Fabrizio L. , Faria J. P. , Martinez Fiorenzano A. , Molinaro M. , Pedani M. 
Published: November 2018

Context. Statistical studies of exoplanets have shown that giant planets are more commonly hosted by metal-rich dwarf stars than low-metallicity stars, while no such correlation is evident for lower mass planets. The search for giant planets around metal-poor stars and the estimate of their occurrence fp is an important element in providing support to models of planet formation.
Aims. We present results from the HARPS-N search for giant planets orbiting metal-poor (− 1.0 ≤[Fe/H] ≤−0.5 dex) stars in the northern hemisphere, complementing a previous HARPS survey on southern stars in order to update the estimate of fp.
Methods. High-precision HARPS-N observations of 42 metal-poor stars were used to search for planetary signals to be fitted using differential evolution Markov chain Monte Carlo single-Keplerian models. We then joined our detections to the results of the previous HARPS survey on 88 metal-poor stars to provide a preliminary estimate of the two-hemisphere fp.

Results. We report the detection of two new giant planets around HD 220197 and HD 233832. The first companion has Msin i = 0.20−0.04+0.07 MJup and an orbital period of 1728−80+162 days, and for the second companion, we find two solutions of equal statistical weight with periods of 2058−40+47 and 4047−117+91 days and minimum masses of 1.78−0.06+0.08 and 2.72−0.23+0.23 MJup, respectively. Joining our two detections with the three from the southern survey, we obtain a preliminary and conservative estimate of the global frequency of fp = 3.84 −1.06+2.45% for giant planets around metal-poor stars.Conclusions. The two new giant planets orbit dwarf stars at the metal-rich end of the HARPS-N metal-poor sample. This corroborates previous results that suggested that giant planet frequency is still a rising function of the host star [Fe/H]. We also note that all detections in the overall sample are giant long-period planets.
All-endoscopic management of benign bone lesions; a case series of 26 cases with minimum of 2 years follow-up
Authors: Farouk Hazem A. , Saladin Mostafa , Senna Wessam Abu , Ebeid Walid 
Published: November 2018

Purpose: Assessment of the functional and oncologic outcomes regarding endoscopic curettage of different benign bone tumor types within variable anatomic locations.Patients and methods: During the period between February 2012 and December 2016, 26 patients with symptomatic intra-osseous benign bony lesions were included. The age ranged from 3 up to 49 years (mean 20), of 14 females and 12 males. The follow-up duration ranged from 26 up to 58 months (mean 41). Functional scoring was done according to the Revised Musculoskeletal Tumour Society Rating Scale. Anatomic locations of the lesions included: 6 cases in the proximal tibia, 6 cases in the distal femur, 4 cases in the calcaneus, 3 cases in the proximal humerus, 3 cases in the distal tibia, 2 cases in the talus, 1 case in the proximal femur, and 1 case in the distal fibula. The procedure used 4 mm 30° scope for endoscopy, and high speed burrs 3.5–5 mm for extended curettage. Autogenous bone grafting was done in 5 cases, and adjuvant material (polymethylmethacrylate) was needed in 7 cases.Results: After exclusion of one case that was lost in the follow-up, the remaining 25 cases showed full functional recovery at a period of 8–12 weeks, and improved mean functional scores from 20.2 to 28.6/30 post-operatively, withpvalue <0.001 which was considered as a statistically significant result. The oncologic outcome showed 24 cases with adequate healing, while 1 case developed recurrence (aneurysmal bone cyst in the proximal tibia) for which, an open revision surgery was performed. Intra-operative fracture occurred in another case with aneurysmal bone cyst of the proximal femur, which was fixed by flexible nails with complete healing.Conclusion: Endoscopic curettage of different types of intra-osseous benign bony lesions proved to be an effective treatment modality with promising oncologic outcome, improved functional scores, and fast functional recovery.
When do patients drive after minimally invasive anterior hip replacements? A single surgeon experience of 212 hip arthroplasties
Authors: Batra Ashish , Gogos Sophia , Nizam Ikram 
Published: November 2018

Introduction: Patients desire to return to normal activities soon after hip arthroplasty, with driving often being an integral component. We aimed to determine when patients resumed driving following a minimally invasive anterior bikini hip replacement and when they returned to work.
Methodology: All consecutive patients undergoing elective primary bikini hip replacements between January 2017 and April 2018 were included in the study. Patients who did not drive were excluded. A detailed questionnaire was sent to patients 3–6 weeks after surgery to record their driving status. Fifty patients were randomly selected to assess flexion at the hip, knee and ankle joints while seated in the driver's seat of their own vehicle.
Results: Altogether 212 anterior bikini total hip replacements (L = 102, R = 108 and 1 bilateral one stage) were performed in 198 patients (F = 129 and M = 69) with a mean age of 69 years. A total of 76% patients returned to driving within the first 3 weeks after surgery, of which 25 (14%) resumed driving within the first post-operative week, 71 (39%) in the second week and 42 (23%) in the third week. Among them, 98.4% stated they were confident when they first started driving and 90.66% stated they were more comfortable driving after surgery than before. Employed patients returned to work within 1–79 days (mean = 24 days).
Conclusion: Surgeons may allow patients to resume driving within 1 week after anterior hip replacement and return to work within 3 weeks if they are medically fit and deemed safe.