bluuebunny/crossref_metadata_2025_split huggingface dataset:
interleukin-11 induces and maintains progenitors of different cell lineages during Xenopus tadpole tail regeneration
Authors: Tsujioka Hiroshi , Kunieda Takekazu , Katou Yuki , Shirahige Katsuhiko , Fukazawa Taro , Kubo Takeo 
Published: September 2017

AbstractUnlike mammals,Xenopus laevistadpoles possess high ability to regenerate their lost organs. In amphibians, the main source of regenerated tissues is lineage-restricted tissue stem cells, but the mechanisms underlying induction, maintenance and differentiation of these stem/progenitor cells in the regenerating organs are poorly understood. We previously reported thatinterleukin-11(il-11) is highly expressed in the proliferating cells of regeneratingXenopustadpole tails. Here, we show thatil-11knockdown (KD) shortens the regenerated tail length, and the phenotype is rescued by forced-il-11-expression in the KD tadpoles. Moreover, marker genes for undifferentiated notochord, muscle, and sensory neurons are downregulated in the KD tadpoles, and the forced-il-11-expression in intact tadpole tails induces expression of these marker genes. Our findings demonstrate thatil-11is necessary for organ regeneration, and suggest that IL-11 plays a key role in the induction and maintenance of undifferentiated progenitors across cell lineages duringXenopustail regeneration.
HIV-1-mediated insertional activation of STAT5B and BACH2 trigger viral reservoir in T regulatory cells
Authors: Cesana Daniela , Santoni de Sio Francesca R. , Rudilosso Laura , Gallina Pierangela , Calabria Andrea , Beretta Stefano , Merelli Ivan , Bruzzesi Elena , Passerini Laura , Nozza Silvia , Vicenzi Elisa , Poli Guido , Gregori Silvia , Tambussi Giuseppe , Montini Eugenio 
Published: September 2017

AbstractHIV-1 insertions targeting BACH2 or MLK2 are enriched and persist for decades in hematopoietic cells from patients under combination antiretroviral therapy. However, it is unclear how these insertions provide such selective advantage to infected cell clones. Here, we show that in 30/87 (34%) patients under combination antiretroviral therapy, BACH2, and STAT5B are activated by insertions triggering the formation of mRNAs that contain viral sequences fused by splicing to their first protein-coding exon. These chimeric mRNAs, predicted to express full-length proteins, are enriched in T regulatory and T central memory cells, but not in other T lymphocyte subsets or monocytes. Overexpression of BACH2 or STAT5B in primary T regulatory cells increases their proliferation and survival without compromising their function. Hence, we provide evidence that HIV-1-mediated insertional activation of BACH2 and STAT5B favor the persistence of a viral reservoir in T regulatory cells in patients under combination antiretroviral therapy.
The WISDOM Study: breaking the deadlock in the breast cancer screening debate
Authors: Esserman Laura J. ,   the WISDOM Study and Athena Investigators, Anton-Culver Hoda , Borowsky Alexander , Brain Susie , Cink Thomas , Crawford Beth , Eklund Martin , Esserman Laura , Fenton Joshua , Heditsian Diane , Hiatt Robert A. , Hogarth Michael , Kaplan Celia , Koenig Barbara , LaCroix Andrea , Larsen Kathryn M. , Lee Vivian , Matthews Jeffrey , Madlensky Lisa , Naeim Arash , Ojeda-Fournier Haydee , Parker Barbara A. , Sepucha Karen , Shieh Yiwey , Stover Fiscalini Allison , Thompson Carlie , Tice Jeffrey , Van ‘T Veer Laura , Wenger Neil , Ziv Elad 
Published: September 2017

AbstractThere are few medical issues that have generated as much controversy as screening for breast cancer. In science, controversy often stimulates innovation; however, the intensely divisive debate over mammographic screening has had the opposite effect and has stifled progress. The same two questions—whether it is better to screen annually or bi-annually, and whether women are best served by beginning screening at 40 or some later age—have been debated for 20 years, based on data generated three to four decades ago. The controversy has continued largely because our current approach to screening assumes all women have the same risk for the same type of breast cancer. In fact, we now know that cancers vary tremendously in terms of timing of onset, rate of growth, and probability of metastasis. In an era of personalized medicine, we have the opportunity to investigate tailored screening based on a woman’s specific risk for a specific tumor type, generating new data that can inform best practices rather than to continue the rancorous debate. It is time to move from debate to wisdom by asking new questions and generating new knowledge. The WISDOM Study (Women Informed to Screen Depending On Measures of risk) is a pragmatic, adaptive, randomized clinical trial comparing a comprehensive risk-based, or personalized approach to traditional annual breast cancer screening. The multicenter trial will enroll 100,000 women, powered for a primary endpoint of non-inferiority with respect to the number of late stage cancers detected. The trial will determine whether screening based on personalized risk is as safe, less morbid, preferred by women, will facilitate prevention for those most likely to benefit, and adapt as we learn who is at risk for what kind of cancer. Funded by the Patient Centered Outcomes Research Institute, WISDOM is the product of a multi-year stakeholder engagement process that has brought together consumers, advocates, primary care physicians, specialists, policy makers, technology companies and payers to help break the deadlock in this debate and advance towards a new, dynamic approach to breast cancer screening.
SATB2/β-catenin/TCF-LEF pathway induces cellular transformation by generating cancer stem cells in colorectal cancer
Authors: Yu Wei , Ma Yiming , Shankar Sharmila , Srivastava Rakesh K. 
Published: September 2017

AbstractRecent studies have demonstrated the involvement of colorectal cancer (CRC) stem cells (CSC) in transformation, cancer progression and metastasis. The main goal of this paper was to examine the molecular mechanisms by which SATB2 induced malignant transformation of colorectal epithelial cells. SATB2 induced malignant transformation and these transformed cells gained the characteristics of CSCs by expressing stem cell markers (CD44, CD133, LGR5 and DCLK1) and transcription factors (c-Myc, Nanog and Sox2). Overexpression of SATB2 in normal colorectal epithelial cells increased cell motility, migration and invasion, which were associated with an increase in N-cadherin and Zeb1, and decrease in E-cadherin expression. SATB2 overexpression also upregulated XIAP and cyclin D1, suggesting its role in cell survival and cell cycle. Furthermore, the expression of SATB2 was positively correlated with β-catenin expression in CRC. In contrary, depletion of SATB2 inhibited cell proliferation, colony formation, cell motility and expression of β-catenin, Snail, Slug, Zeb1 and N-cadherin, and upregulated E-cadherin. Furthermore, SATB2 silencing inhibited the expression of stem cell markers, pluripotency maintaining transcription factors, cell cycle and cell proliferation/survival genes and TCF/LEF targets. Finally, β-catenin/TCF-LEF pathway mediated the biological effects of SATB2 in CSCs. These studies support the role of SATB2/β-catenin/TCF-LEF pathway in transformation and carcinogenesis.
Hyaluronic acid based extracellular matrix regulates surface expression of GluN2B containing NMDA receptors
Authors: Schweitzer Barbara , Singh Jeet , Fejtova Anna , Groc Laurent , Heine Martin , Frischknecht Renato 
Published: September 2017

AbstractCortical areas of the juvenile rodent brain display a high degree of structural and functional plasticity, which disappears later in development. Coincident with the decline of plasticity 1) the hyaluronic acid-based extracellular matrix (ECM) of the brain, which stabilizes synapses and neuronal circuit is formed and 2) N-methyl-D-aspartate subtype of ionotropic glutamate receptors (NMDARs) implied in synaptic plasticity switch from mainly GluN2B to GluN2A subunit-containing receptors. Here we tested the hypothesis that ECM influences the NMDAR subunit composition in dissociated neuronal cultures. Experimental removal of ECM using hyaluronidase induced an increase in surface expression of GluN2B. This was due to decreased endocytosis of surface GluNB-containing receptors. We further found a reduction in phosphorylation at Tyr1472, which negatively regulates their binding to the endocytotic AP2 complex. We propose that maturation of ECM could induce switch in NMDAR composition necessary for normal adult synaptic plasticity and that increased expression of GluN2B contributes to rejuvenation of plasticity after ECM removal in vivo.
LNA effects on DNA binding and conformation: from single strand to duplex and triplex structures
Authors: Pabon-Martinez Y. Vladimir , Xu You , Villa Alessandra , Lundin Karin E. , Geny Sylvain , Nguyen Chi-Hung , Pedersen Erik B. , Jørgensen Per T. , Wengel Jesper , Nilsson Lennart , Smith C. I. Edvard , Zain Rula 
Published: September 2017

AbstractThe anti-gene strategy is based on sequence-specific recognition of double-strand DNA by triplex forming (TFOs) or DNA strand invading oligonucleotides to modulate gene expression. To be efficient, the oligonucleotides (ONs) should target DNA selectively, with high affinity. Here we combined hybridization analysis and electrophoretic mobility shift assay with molecular dynamics (MD) simulations to better understand the underlying structural features of modified ONs in stabilizing duplex- and triplex structures. Particularly, we investigated the role played by the position and number of locked nucleic acid (LNA) substitutions in the ON when targeting a c-MYC or FXN (Frataxin) sequence. We found that LNA-containing single strand TFOs are conformationally pre-organized for major groove binding. Reduced content of LNA at consecutive positions at the 3′-end of a TFO destabilizes the triplex structure, whereas the presence of Twisted Intercalating Nucleic Acid (TINA) at the 3′-end of the TFO increases the rate and extent of triplex formation. A triplex-specific intercalating benzoquinoquinoxaline (BQQ) compound highly stabilizes LNA-containing triplex structures. Moreover, LNA-substitution in the duplex pyrimidine strand alters the double helix structure, affecting x-displacement, slide and twist favoring triplex formation through enhanced TFO major groove accommodation. Collectively, these findings should facilitate the design of potent anti-gene ONs.
A global Staphylococcus aureus proteome resource applied to the in vivo characterization of host-pathogen interactions
Authors: Michalik Stephan , Depke Maren , Murr Annette , Gesell Salazar Manuela , Kusebauch Ulrike , Sun Zhi , Meyer Tanja C. , Surmann Kristin , Pförtner Henrike , Hildebrandt Petra , Weiss Stefan , Palma Medina Laura Marcela , Gutjahr Melanie , Hammer Elke , Becher Dörte , Pribyl Thomas , Hammerschmidt Sven , Deutsch Eric W. , Bader Samuel L. , Hecker Michael , Moritz Robert L. , Mäder Ulrike , Völker Uwe , Schmidt Frank 
Published: September 2017

AbstractData-independent acquisition mass spectrometry promises higher performance in terms of quantification and reproducibility compared to data-dependent acquisition mass spectrometry methods. To enable high-accuracy quantification of Staphylococcus aureus proteins, we have developed a global ion library for data-independent acquisition approaches employing high-resolution time of flight or Orbitrap instruments for this human pathogen. We applied this ion library resource to investigate the time-resolved adaptation of S. aureus to the intracellular niche in human bronchial epithelial cells and in a murine pneumonia model. In epithelial cells, abundance changes for more than 400 S. aureus proteins were quantified, revealing, e.g., the precise temporal regulation of the SigB-dependent stress response and differential regulation of translation, fermentation, and amino acid biosynthesis. Using an in vivo murine pneumonia model, our data-independent acquisition quantification analysis revealed for the first time the in vivo proteome adaptation of S. aureus. From approximately 2.15 × 105
S. aureus cells, 578 proteins were identified. Increased abundance of proteins required for oxidative stress response, amino acid biosynthesis, and fermentation together with decreased abundance of ribosomal proteins and nucleotide reductase NrdEF was observed in post-infection samples compared to the pre-infection state.
Insulin, glucagon and somatostatin stores in the pancreas of subjects with type-2 diabetes and their lean and obese non-diabetic controls
Authors: Henquin Jean-Claude , Ibrahim Majeed M. , Rahier Jacques 
Published: September 2017

AbstractIn type-2 diabetes, both insufficient insulin and excessive glucagon secretion contribute to hyperglycemia. We compared insulin, glucagon and somatostatin stores in pancreas obtained at autopsy of 20 lean and 19 obese non-diabetic (ND), and 18 type-2 diabetic (T2D) subjects. From concentrations and pancreas weight, total content of hormones was calculated. Insulin content was 35% lower in T2D than ND subjects (7.4 versus 11.3 mg), whereas glucagon content was similar (0.76 versus 0.81 mg). The higher ratio of glucagon/insulin contents in T2D was thus explained by the decrease in insulin. With increasing BMI of ND subjects, insulin and glucagon contents respectively tended to increase and decrease, resulting in a lower glucagon/insulin ratio in obesity. With aging, insulin and glucagon contents did not significantly change in ND subjects but declined in T2D subjects, without association with the duration of diabetes or type of treatment. The somatostatin content was lower in T2D than ND subjects (0.027 versus 0.038 mg), but ratios somatostatin/insulin and somatostatin/glucagon were not different. In conclusion, insulin stores are about 1/3 lower in T2D than ND subjects, whereas glucagon stores are unchanged. Abnormal secretion of each hormone in type-2 diabetes cannot be attributed to major alterations in their pancreatic reserves.
The intestinal phosphate transporter NaPi-IIb (Slc34a2) is required to protect bone during dietary phosphate restriction
Authors: Knöpfel Thomas , Pastor-Arroyo Eva M. , Schnitzbauer Udo , Kratschmar Denise V. , Odermatt Alex , Pellegrini Giovanni , Hernando Nati , Wagner Carsten A. 
Published: September 2017

AbstractNaPi-IIb/Slc34a2 is a Na+-dependent phosphate transporter that accounts for the majority of active phosphate transport into intestinal epithelial cells. Its abundance is regulated by dietary phosphate, being high during dietary phosphate restriction. Intestinal ablation of NaPi-IIb in mice leads to increased fecal excretion of phosphate, which is compensated by enhanced renal reabsorption. Here we compared the adaptation to dietary phosphate of wild type (WT) and NaPi-IIb−/− mice. High phosphate diet (HPD) increased fecal and urinary excretion of phosphate in both groups, though NaPi-IIb−/− mice still showed lower urinary excretion than WT. In both genotypes low dietary phosphate (LDP) resulted in reduced fecal excretion and almost undetectable urinary excretion of phosphate. Consistently, the expression of renal cotransporters after prolonged LDP was similar in both groups. Plasma phosphate declined more rapidly in NaPi-IIb−/− mice upon LDP, though both genotypes had comparable levels of 1,25(OH)2vitamin D3, parathyroid hormone and fibroblast growth factor 23. Instead, NaPi-IIb−/− mice fed LDP had exacerbated hypercalciuria, higher urinary excretion of corticosterone and deoxypyridinoline, lower bone mineral density and higher number of osteoclasts. These data suggest that during dietary phosphate restriction NaPi-IIb-mediated intestinal absorption prevents excessive demineralization of bone as an alternative source of phosphate.
Neonicotinoids act like endocrine disrupting chemicals in newly-emerged bees and winter bees
Authors: Baines Danica , Wilton Emily , Pawluk Abbe , de Gorter Michael , Chomistek Nora 
Published: September 2017

AbstractAccumulating evidence suggests that neonicotinoids may have long-term adverse effects on bee health, yet our understanding of how this could occur is incomplete. Pesticides can act as endocrine disrupting chemicals (EDCs) in animals providing characteristic multiphasic dose-response curves and non-lethal endpoints in toxicity studies. However, it is not known if neonicotinoids act as EDCs in bees. To address this issue, we performed oral acute and chronic toxicity studies including concentrations recorded in nectar and pollen, applying acetamiprid, clothianidin, imidacloprid, and thiamethoxam to bumble bees, honey bees and leafcutter bees, the three most common bee species managed for pollination. In acute toxicity studies, late-onset symptoms, such as ataxia, were recorded as non-lethal endpoints for all three bee species. Clothianidin and thiamethoxam produced biphasic dose-response curves for all three bee species. Clothianidin and thiamethoxam were extremely toxic to winter worker honey bees prior to brood production in spring, making this the most sensitive bee stage identified to date. Chronic exposure to field-realistic levels of neonicotinoids reduced bee survival and caused significant late-onset symptoms for all three bee species. Given these findings, neonicotinoid risk should be reevaluated to address the EDC-like behavior and the sensitivity of winter worker honey bees.
Thin zeolite laminates for rapid and energy-efficient carbon capture
Authors: Akhtar Farid , Ogunwumi Steven , Bergström Lennart 
Published: September 2017

AbstractThin, binder-less zeolite NaX laminates, with thicknesses ranging between 310 to 750 μm and widths exceeding 50 mm and biaxial tensile strength in excess of 3 MPa, were produced by pulsed current processing. The NaX laminates displayed a high CO2 adsorption capacity and high binary CO2-over-N2 and CO2-over-CH4 selectivity, suitable for CO2 capture from flue gas and upgrading of raw biogas. The thin laminates displayed a rapid CO2 uptake; NaX laminates with a thickness of 310 μm were saturated to 40% of their CO2 capacity within 24 seconds. The structured laminates of 310 μm thickness and 50 mm thickness would offer low pressure drop and efficient carbon capture performance in a laminate-based swing adsorption technology.
Evaluating strategies for reversing CRISPR-Cas9 gene drives
Authors: Vella Michael R. , Gunning Christian E. , Lloyd Alun L. , Gould Fred 
Published: September 2017

AbstractA gene drive biases inheritance of a gene so that it increases in frequency within a population even when the gene confers no fitness benefit. There has been renewed interest in environmental releases of engineered gene drives due to recent proof of principle experiments with the CRISPR-Cas9 system as a drive mechanism. Release of modified organisms, however, is controversial, especially when the drive mechanism could theoretically alter all individuals of a species. Thus, it is desirable to have countermeasures to reverse a drive if a problem arises. Several genetic mechanisms for limiting or eliminating gene drives have been proposed and/or developed, including synthetic resistance, reversal drives, and immunizing reversal drives. While predictions about efficacy of these mechanisms have been optimistic, we lack detailed analyses of their expected dynamics. We develop a discrete time model for population genetics of a drive and proposed genetic countermeasures. Efficacy of drive reversal varies between countermeasures. For some parameter values, the model predicts unexpected behavior including polymorphic equilibria and oscillatory dynamics. The timing and number of released individuals containing a genetic countermeasure can substantially impact outcomes. The choice among countermeasures by researchers and regulators will depend on specific goals and population parameters of target populations.
Rapid synthesis and decoration of reduced graphene oxide with gold nanoparticles by thermostable peptides for memory device and photothermal applications
Authors: Otari Sachin V. , Kumar Manoj , Anwar Muhammad Zahid , Thorat Nanasaheb D. , Patel Sanjay K. S. , Lee Dongjin , Lee Jai Hyo , Lee Jung-Kul , Kang Yun Chan , Zhang Liaoyuan 
Published: September 2017

AbstractThis article presents novel, rapid, and environmentally benign synthesis method for one-step reduction and decoration of graphene oxide with gold nanoparticles (NAuNPs) by using thermostable antimicrobial nisin peptides to form a gold-nanoparticles-reduced graphene oxide (NAu-rGO) nanocomposite. The formed composite material was characterized by UV/Vis spectroscopy, X-ray diffraction, Raman spectroscopy, X-ray photoelectron spectroscopy, field emission scanning electron microscopy, and high-resolution transmission electron microscopy (HR-TEM). HR-TEM analysis revealed the formation of spherical AuNPs of 5–30 nm in size on reduced graphene oxide (rGO) nanosheets. A non-volatile-memory device was prepared based on a solution-processed ZnO thin-film transistor fabricated by inserting the NAu-rGO nanocomposite in the gate dielectric stack as a charge trapping medium. The transfer characteristic of the ZnO thin-film transistor memory device showed large clockwise hysteresis behaviour because of charge carrier trapping in the NAu-rGO nanocomposite. Under positive and negative bias conditions, clear positive and negative threshold voltage shifts occurred, which were attributed to charge carrier trapping and de-trapping in the ZnO/NAu-rGO/SiO2 structure. Also, the photothermal effect of the NAu-rGO nanocomposites on MCF7 breast cancer cells caused inhibition of ~80% cells after irradiation with infrared light (0.5 W cm−2) for 5 min.
The syntactic organization of pasta-eating and the structure of reach movements in the head-fixed mouse
Authors: Whishaw Ian Q. , Faraji Jamshid , Kuntz Jessica R. , Mirza Agha Behroo , Metz Gerlinde A. S. , Mohajerani Majid H. 
Published: September 2017

AbstractMice are adept in the use of their hands for activities such as feeding, which has led to their use in investigations of the neural basis of skilled-movements. We describe the syntactic organization of pasta-eating and the structure of hand movements used for pasta manipulation by the head-fixed mouse. An ethogram of mice consuming pieces of spaghetti reveals that they eat in bite/chew bouts. A bout begins with pasta lifted to the mouth and then manipulated with hand movements into a preferred orientation for biting. Manipulation involves many hand release-reach movements, each with a similar structure. A hand is advanced from a digit closed and flexed (collect) position to a digit extended and open position (overgrasp) and then to a digit closed and flexed (grasp) position. Reach distance, hand shaping, and grasp patterns featuring precision grasps or whole hand grasps are related. To bite, mice display hand preference and asymmetric grasps; one hand (guide grasp) directs food into the mouth and the other stabilizes the pasta for biting. When chewing after biting, the hands hold the pasta in a symmetric resting position. Pasta-eating is organized and features structured hand movements and so lends itself to the neural investigation of skilled-movements.