bluuebunny/crossref_metadata_2025_split huggingface dataset:
IGF2BP2 regulates DANCR by serving as an N6-methyladenosine reader
Authors: Hu Xiaoge , Peng Wan-Xin , Zhou Huaixiang , Jiang Jiahong , Zhou Xinchun , Huang Dongsheng , Mo Yin-Yuan , Yang Liu 
Published: December 2019

AbstractThe major function of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is to regulate cell metabolism. However, emerging evidence indicates that IGF2BP2 plays a role in cancer, but the underlying mechanism is largely unknown. Here we showed that upregulation of IGF2BP2 is associated with poor outcomes of pancreatic cancer patients and suppression of IGF2BP2 inhibits cell proliferation. We further showed that IGF2BP2 regulates lncRNA DANCR. Ectopic expression IGF2BP2 enhances, whereas knockdown (KD) or knockout (KO) of IGF2BP2 suppresses DANCR expression. Moreover, in vivo RNA precipitation and reciprocal RNA immunoprecipitation revealed that IGF2BP2 interacts with DANCR. DANCR promotes cell proliferation and stemness-like properties. Experiments with xenograft models revealed that while ectopic expression of DANCR promotes, DANCR KO suppresses tumor growth. Mechanistically, DANCR is modified at N6-methyladenosine (m6A) and mutagenesis assay identified that adenosine at 664 of DANCR is critical to the interaction between IGF2BP2 and DANCR where IGF2BP2 serves a reader for m6A modified DANCR and stabilizes DANCR RNA. Together, these results suggest that DANCR is a novel target for IGF2BP2 through m6A modification, and IGF2BP2 and DANCR work together to promote cancer stemness-like properties and pancreatic cancer pathogenesis.
LRRC8/VRAC channels exhibit a noncanonical permeability to glutathione, which modulates epithelial-to-mesenchymal transition (EMT)
Authors: Friard Jonas , Corinus Alain , Cougnon Marc , Tauc Michel , Pisani Didier F. , Duranton Christophe , Rubera Isabelle 
Published: December 2019

AbstractVolume-regulated anion channels (VRAC) are chloride channels activated in response to osmotic stress to regulate cellular volume and also participate in other cellular processes, including cell division and cell death. Recently, members of the LRRC8 family have been identified as the main contributors of VRAC conductance. LRRC8/VRAC is permeable to chloride ions but also exhibits significant permeability to various substrates that vary strongly in charge and size. In this study, we explored the intriguing ability of LRRC8/VRAC to transport glutathione (GSH), the major cellular reactive oxygen species (ROS) scavenger, and its involvement in epithelial-to-mesenchymal transition (EMT), a cellular process in which cellular oxidative status is a crucial step. First, in HEK293-WT cells, we showed that a hypotonic condition induced LRRC8/VRAC-dependent GSH conductance (PGSH/PCl of ~0.1) and a marked decrease in intracellular GSH content. GSH currents and GSH intracellular decrease were both inhibited by DCPIB, an inhibitor of LRRC8/VRAC, and were not observed in HEK293-LRRC8A KO cells. Then, we induced EMT by exposing renal proximal tubule epithelial cells to the pleiotropic growth factor TGFβ1, and we measured the contribution of LRRC8/VRAC in this process by measuring (i) EMT marker expression (assessed both at the gene and protein levels), (ii) cell morphology and (iii) the increase in migration ability. Interestingly, pharmacologic targeting of LRRC8/VRAC (DCPIB) or RNA interference-mediated inhibition (LRRC8A siRNA) attenuated the TGFβ1-induced EMT response by controlling GSH and ROS levels. Interestingly, TGFβ1 exposure triggered DCPIB-sensitive chloride conductance. These results suggest that LRRC8/VRAC, due to its native permeability to GSH and thus its ability to modulate ROS levels, plays a critical role in EMT and might contribute to other physiological and pathophysiological processes associated with oxidative stress.
Accumulation and fractionation of rare earth elements are conserved traits in the Phytolacca genus
Authors: Grosjean Nicolas , Le Jean Marie , Berthelot Charlotte , Chalot Michel , Gross Elisabeth Maria , Blaudez Damien 
Published: December 2019

AbstractRare earth elements (REEs) are now considered emerging pollutants in the environment. Phytolacca americana, an REE hyperaccumulating plant, has been proposed for the remediation of REE-contaminated soils. However, there is no REE-related information for other Phytolacca species. Here, we examined five species (P. americana, P. acinosa, P. clavigera, P. bogotensis, and P. icosandra) for their response to REEs. REE accumulation and fractionation traits both occurred on the same order of magnitude among the five species. Heavy REEs were preferentially transferred to leaves relative to light REEs. Regardless of the species, lateral root length and chlorophyll content decreased under REE exposure, and lateral roots and foliar anthocyanins increased. However, plants did not experience or only slightly experienced oxidative stress. Finally, REE exposure strongly modulated the ionome of roots and, to a lesser extent, that of leaves, with a negative correlation between REE and Mn contents. In conclusion, our study provides new data on the response of several Phytolacca species to REEs. Moreover, we highlighted that the REE accumulation trait was conserved among Phytolacca species. Thus, we provide valuable information for the phytoremediation of REE-contaminated sites since the most appropriate Phytolacca species could be selected depending on the climatic/pedological area to be remediated.
Unpacking the aggregation-oligomerization-fibrillization process of naturally-occurring hIAPP amyloid oligomers isolated directly from sera of children with obesity or diabetes mellitus
Authors: Altamirano-Bustamante Myriam M. , Altamirano-Bustamante Nelly F. , Larralde-Laborde Mateo , Lara-Martínez Reyna , Leyva-García Edgar , Garrido-Magaña Eulalia , Rojas Gerardo , Jiménez-García Luis Felipe , Revilla-Monsalve Cristina , Altamirano Perla , Calzada-León Raúl 
Published: December 2019

AbstractThe formation of amyloid oligomers and fibrils of the human islet amyloid polypeptide (hIAPP) has been linked with β- cell failure and death which causes the onset, progression, and comorbidities of diabetes. We begin to unpack the aggregation-oligomerization-fibrillization process of these oligomers taken from sera of pediatric patients. The naturally occurring or real hIAPP (not synthetic) amyloid oligomers (RIAO) were successfully isolated, we demonstrated the presence of homo (dodecamers, hexamers, and trimers) and hetero-RIAO, as well as several biophysical characterizations which allow us to learn from the real phenomenon taking place. We found that the aggregation/oligomerization process is active in the sera and showed that it happens very fast. The RIAO can form fibers and react with anti-hIAPP and anti-amyloid oligomers antibodies. Our results opens the epistemic horizon and reveal real differences between the four groups (Controls vs obesity, T1DM or T2DM) accelerating the process of understanding and discovering novel and more efficient prevention, diagnostic, transmission and therapeutic pathways.
Modeling of neotame and fructose thermochemistry: Comparison with mono and divalent metal ions by Computational and experimental approach
Authors: Sharma Deepali , Kanchi Suvardhan , Bathinapatla Ayyappa , Inamuddin  , Asiri Abdullah M. 
Published: December 2019

AbstractThe metal complexes can demonstrate various interesting biological activities in the human body. However, the role of certain metal ions for specific cell activities is still subject to debate. This study is aimed at comparing the thermochemical properties of neotame (artificial sweetener) and α, β-fructose in gas phase and water medium. The interaction of α and β-fructose, neotame with monovalent and divalent metal ions was studied and comprehended by density functional theory (DFT) using B3LYP functional, 6–311 + G (d, p) and D3 basis set. Metal ion affinities (MIA) values depicted that ionic radius of metal ions played an important role in the interaction of α, β-fructose and neotame. The ∆G parameter was calculated to predict and understand the interaction of metal ions with α and β-fructose, neotame. The results suggested that the presence of hydroxyl groups and oxygen atoms in sugar molecules acted as preferred sites for the binding and interaction of mono and divalent ions. For the first time computational study has been introduced in the present study to review the progress in the application of metal binding with sugar molecules especially with neotame. Moreover, voltammetric behaviour of neotame-Zn2+ was studied using cyclic and differential pulse voltammetry. The obtained results suggest that the peak at −1.13 V is due to the reduction of Zn2+ in 0.1 M phosphate buffer medium at pH 5.5. Whereas, addition of 6-fold higher concentration of neotame to the ZnCl2.2H2O resulted in a new irreversible cathodic peak at −0.83, due to the reduction of neotame-Zn2+ complex. The Fourier transform infrared spectroscopy (FTIR) results indicates that the β-amino group (-NH) and carboxyl carbonyl (-C = O) groups of neotame is participating in the chelation process, which is further supported by DFT studies. The findings of this study identify the efficient chelation factors as major contributors into metal ion affinities, with promising possibilities to determine important biological processes in cell wall and glucose transmembrane transport.
New insights in oocyte dynamics shed light on the complexities associated with fish reproductive strategies
Authors: Serrat Alba , Saborido-Rey Fran , Garcia-Fernandez Cristina , Muñoz Marta , Lloret Josep , Thorsen Anders , Kjesbu Olav Sigurd 
Published: December 2019

AbstractInformation on temporal variations in stock reproductive potential (SRP) is essential in fisheries management. Despite this relevance, fundamental understanding of egg production variability remains largely unclear due to difficulties in tracking the underlying complex fluctuations in early oocyte recruitment that determines fecundity. We applied advanced oocyte packing density theory to get in-depth, quantitative insights across oocyte stages and seasons, selecting the commercially valuable European hake (Merluccius merluccius) as a case study. Our work evidenced sophisticated seasonal oocyte recruitment dynamics and patterns, mostly driven by a low-cost predefinition of fecundity as a function of fish body size, likely influenced also by environmental cues. Fecundity seems to be defined at a much earlier stage of oocyte development than previously thought, implying a quasi-determinate – rather than indeterminate – fecundity type in hake. These results imply a major change in the conceptual approach to reproductive strategies in teleosts. These findings not only question the current binary classification of fecundity as either determinate or indeterminate, but also suggest that current practices regarding potential fecundity estimation in fishes should be complemented with studies on primary oocyte dynamics. Accordingly, the methodology and approach adopted in this study may be profitably applied for unravelling some of the complexities associated with oocyte recruitment and thereby SRP variability.
Statistical characteristics of amino acid covariance as possible descriptors of viral genomic complexity
Authors: Sruthi C. K. , Prakash Meher K. 
Published: December 2019

AbstractAt the sequence level it is hard to describe the complexity of viruses which allows them to challenge host immune system, some for a few weeks and others up to a complete compromise. Paradoxically, viral genomes are both complex and simple. Complex because amino acid mutation rates are very high, and yet viruses remain functional. Simple because they have barely around 10 types of proteins, so viral protein-protein interaction networks are not insightful. In this work we use fine-grained amino acid level information and their evolutionary characteristics obtained from large-scale genomic data to develop a statistical panel, towards the goal of developing quantitative descriptors for the biological complexity of viruses. Networks were constructed from pairwise covariation of amino acids and were statistically analyzed. Three differentiating factors arise: predominantly intra- vs inter-protein covariance relations, the nature of the node degree distribution and network density. Interestingly, the covariance relations were primarily intra-protein in avian influenza and inter-protein in HIV. The degree distributions showed two universality classes: a power-law with exponent −1 in HIV and avian-influenza, random behavior in human flu and dengue. The calculated covariance network density correlates well with the mortality strengths of viruses on the viral-Richter scale. These observations suggest the potential utility of the statistical metrics for describing the covariance patterns in viruses. Our host-virus interaction analysis point to the possibility that host proteins which can interact with multiple viral proteins may be responsible for shaping the inter-protein covariance relations. With the available data, it appears that network density might be a surrogate for the virus Richter scale, however the hypothesis needs a re-examination when large scale complete genome data for more viruses becomes available.
Tsunami records of the last 8000 years in the Andaman Island, India, from mega and large earthquakes: Insights on recurrence interval
Authors: Malik Javed N. , Johnson Frango C. , Khan Afzal , Sahoo Santiswarup , Irshad Roohi , Paul Debajyoti , Arora Shreya , Baghel Pankaj Kumar , Chopra Sundeep 
Published: December 2019

AbstractAs many as seven tsunamis from the past 8000 years are evidenced by sand sheets that rest on buried wetland soils at Badabalu, southern Andaman Island, along northern part of the fault rupture of the giant 2004 Aceh-Andaman earthquake. The uppermost of these deposits represents the 2004 tsunami. Underlying deposits likely correspond to historical tsunamis of 1881, 1762, and 1679 CE, and provide evidence for prehistoric tsunamis in 1300–1400 CE, in 2000–3000 and 3020–1780 BCE, and before 5600–5300 BCE. The sequence includes an unexplained hiatus of two or three millennia ending around 1400 CE, which could be attributed to accelerated erosion due to Relative Sea-Level (RSL) fall at ~3500 BP. A tsunami in 1300–1400, comparable to the one in 2004, was previously identified geologically on other Indian Ocean shores. The tsunamis assigned to 1679, 1762, and 1881, by contrast, were more nearly confined to the northeast Indian Ocean. Sources have not been determined for the three earliest of the inferred tsunamis. We suggest a recurrence of 420–750 years for mega-earthquakes having different source, and a shorter interval of 80–120 years for large magnitude earthquakes.
Novel Bead-Based Epitope Assay is a sensitive and reliable tool for profiling epitope-specific antibody repertoire in food allergy
Authors: Suprun Maria , Getts Robert , Raghunathan Rohit , Grishina Galina , Witmer Marc , Gimenez Gustavo , Sampson Hugh A. , Suárez-Fariñas Mayte 
Published: December 2019

AbstractIdentification of allergenic IgE epitopes is instrumental for the development of novel diagnostic and prognostic methods in food allergy. In this work, we present the quantification and validation of a Bead-Based Epitope Assay (BBEA) that through multiplexing of epitopes and multiple sample processing enables completion of large experiments in a short period of time, using minimal quantities of patients’ blood. Peptides that are uniquely coupled to beads are incubated with serum or plasma samples, and after a secondary fluorophore-labeled antibody is added, the level of fluorescence is quantified with a Luminex reader. The signal is then normalized and converted to epitope-specific antibody binding values. We show that the effect of technical artifacts, i.e. well position or reading order, is minimal; and batch effects - different individual microplate runs - can be easily estimated and eliminated from the data. Epitope-specific antibody binding quantified with BBEA is highly reliable, reproducible and has greater sensitivity of epitope detection compared to peptide microarrays. IgE directed at allergenic epitopes is a sensitive biomarker of food allergy and can be used to predict allergy severity and phenotypes; and quantification of the relationship between epitope-specific IgE and IgG4 can further improve our understanding of the immune mechanisms behind allergic sensitization.
Inter-relationships between Gender, Frailty and 10-Year Survival in Older Italian Adults: an observational longitudinal study
Authors: Corbi Graziamaria , Cacciatore Francesco , Komici Klara , Rengo Giuseppe , Vitale Dino Franco , Furgi Giuseppe , Pagano Gennaro , Bencivenga Leonardo , Davinelli Sergio , Ferrara Nicola 
Published: December 2019

AbstractAim of the present study was to assess the impact of gender on the relationship between long-term mortality and clinical frailty. In an observational, longitudinal study on 10-year mortality, we examined 1284 subjects. The Frailty Staging System was used to assess frailty. The Cox model was employed to assess variables independently associated with survival using a backward stepwise algorithm. To investigate the possible interactions between gender and the selected variables, an extension of the multivariable fractional polynomial algorithm was adopted. Women were more likely to be older, have a higher disability, present with more comorbidities, consume more drugs, be frail and have a higher rate of survival at the follow-up than were men. At the Cox multivariate analysis only age (HR 2.26), female gender (HR 0.43), and number of drugs (HR 1.57) were significant and independent factors associated with all-cause mortality. In the survival analyses, only frailty (vs no frailty) showed significant interaction with gender (p < 0.001, HR = 1.92). While the presence of frailty reduced the survival rate in women, no effect was observed in men. Importantly, frail women showed higher survival rates than did both frail and no frail men. The main finding of the present study is that gender shapes up the association between frailty and long-term survival rates.
Postsynaptic CaV1.1-driven calcium signaling coordinates presynaptic differentiation at the developing neuromuscular junction
Authors: Kaplan Mehmet Mahsum , Flucher Bernhard E. 
Published: December 2019

AbstractProper formation of neuromuscular synapses requires the reciprocal communication between motor neurons and muscle cells. Several anterograde and retrograde signals involved in neuromuscular junction formation are known. However the postsynaptic mechanisms regulating presynaptic differentiation are still incompletely understood. Here we report that the skeletal muscle calcium channel (CaV1.1) is required for motor nerve differentiation and that the mechanism by which CaV1.1 controls presynaptic differentiation utilizes activity-dependent calcium signaling in muscle. In mice lacking CaV1.1 or CaV1.1-driven calcium signaling motor nerves are ectopically located and aberrantly defasciculated. Axons fail to recognize their postsynaptic target structures and synaptic vesicles and active zones fail to correctly accumulate at the nerve terminals opposite AChR clusters. These presynaptic defects are independent of aberrant AChR patterning and more sensitive to deficient calcium signals. Thus, our results identify CaV1.1-driven calcium signaling in muscle as a major regulator coordinating multiple aspects of presynaptic differentiation at the neuromuscular synapse.
Running Stride Length And Rate Are Changed And Mechanical Efficiency Is Preserved After Cycling In Middle-Level Triathletes
Authors: da Rosa Rodrigo Gomes , Oliveira Henrique Bianchi de , Ardigò Luca Paolo , Gomeñuka Natalia Andrea , Fischer Gabriela , Peyré-Tartaruga Leonardo Alexandre 
Published: December 2019

AbstractAlthough cycling impairs the subsequent metabolic cost and performance of running in some triathletes, the consequences on mechanical efficiency (Eff) and kinetic and potential energy fluctuations of the body center of mass are still unknown. The aim of this study was to investigate the effects of previous cycling on the cost-of-transport, Eff, mechanical energy fluctuations (Wtot), spring stiffness (Kleg and Kvert) and spatiotemporal parameters. Fourteen middle-level triathletes (mean ± SD: maximal oxygen uptake, $$\dot{{\rm{V}}}$$

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̇

O2max = 65.3 ± 2.7 ml.kg−1.min−1, age = 30 ± 5 years, practice time = 6.8 ± 3.0 years) performed four tests. Two maximal oxygen uptake tests on a cycle ergometer and treadmill, and two submaximal 20-minute running tests (14 km.h−1) with (prior-cycling) and without (control) a previous submaximal 30-minute cycling test. No differences were observed between the control and post-cycling groups in Eff or Wtot. The Eff remains unchanged between conditions. On the other hand, the Kvert (20.2 vs 24.4 kN.m−1) and Kleg (7.1 vs 8.2 kN.m−1, p < 0.05) were lower and the cost-of-transport was higher (p = 0.018, 3.71 vs 3.31 J.kg−1.m−1) when running was preceded by cycling. Significantly higher stride frequency (p < 0.05, 1.46 vs 1.43 Hz) and lower stride length (p < 0.05, 2.60 vs 2.65 m) were observed in the running after cycling condition in comparison with control condition. Mechanical adjustments were needed to maintain the Eff, even resulting in an impaired metabolic cost after cycling performed at moderate intensity. These findings are compatible with the concept that specific adjustments in spatiotemporal parameters preserve the Eff when running is preceded by cycling in middle-level triathletes, though the cost-of-transport increased.
Vocal individuality of Holstein-Friesian cattle is maintained across putatively positive and negative farming contexts
Authors: Green Alexandra , Clark Cameron , Favaro Livio , Lomax Sabrina , Reby David 
Published: December 2019

AbstractCattle mother-offspring contact calls encode individual-identity information; however, it is unknown whether cattle are able to maintain individuality when vocalising to familiar conspecifics over other positively and negatively valenced farming contexts. Accordingly, we recorded 333 high-frequency vocalisations from 13 Holstein-Friesian heifers during oestrus and anticipation of feed (putatively positive), as well as denied feed access and upon both physical and physical & visual isolation from conspecifics (putatively negative). We measured 21 source-related and nonlinear vocal parameters and stepwise discriminant function analyses (DFA) were performed. Calls were divided into positive (n = 170) and negative valence (n = 163) with each valence acting as a ‘training set’ to classify calls in the oppositely valenced ‘test set’. Furthermore, MANOVAs were conducted to determine which vocal parameters were implicated in individual distinctiveness. Within the putatively positive ‘training set’, the cross-validated DFA correctly classified 68.2% of the putatively positive calls and 52.1% of the putatively negative calls to the correct individual, respectively. Within the putatively negative ‘training set’, the cross-validated DFA correctly assigned 60.1% of putatively negative calls and 49.4% of putatively positive calls to the correct individual, respectively. All DFAs exceeded chance expectations indicating that vocal individuality of high-frequency calls is maintained across putatively positive and negative valence, with all vocal parameters except subharmonics responsible for this individual distinctiveness. This study shows that cattle vocal individuality of high-frequency calls is stable across different emotionally loaded farming contexts. Individual distinctiveness is likely to attract social support from conspecifics, and knowledge of these individuality cues could assist farmers in detecting individual cattle for welfare or production purposes.