bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin secretion impairment in Sirt6 knockout pancreatic β cells is mediated by suppression of the FoxO1-Pdx1-Glut2 pathway
Authors: Song Mi-Young , Wang Jie , Ka Sun-O , Bae Eun Ju , Park Byung-Hyun 
Published: July 2016

AbstractSirtuin 6 (Sirt6), a chromatin associated class III deacetylase, controls whole-body energy homeostasis and has a critical role in glucose-stimulated insulin secretion (GSIS) in pancreatic β cells. However, its underlying molecular mechanism remains poorly understood. To gain further insights, we studied the pathway by which Sirt6 regulates GSIS utilizing mice lacking Sirt6 in their β cells (βS6KO). Further, we overexpressed wild type or deacetylase-inactive mutant Sirt6 in isolated islets as well as in MIN6 cells. We confirmed that βS6KO mice developed glucose intolerance with severely impaired GSIS. Gene expression analysis of knockout islets and overexpression studies demonstrated that Sirt6 deacetylates forkhead box protein O1 (FoxO1) to trigger its nuclear export and releases its transcriptional repression of key glucose sensing genes such as Pdx1 and Glut2. Ectopic overexpression of Sirt6 in knockout islets resulted in rescue of the defective insulin secretion and restoration of the expression of Pdx1 and Glut2. These results show that Sirt6 in pancreatic β cells deacetylates FoxO1 and subsequently increases the expression of Pdx1 and Glut2 to maintain the glucose-sensing ability of pancreatic β cells and systemic glucose tolerance.
Structure-Activity Analysis of Gram-positive Bacterium-producing Lasso Peptides with Anti-mycobacterial Activity
Authors: Inokoshi Junji , Koyama Nobuhiro , Miyake Midori , Shimizu Yuji , Tomoda Hiroshi 
Published: July 2016

AbstractLariatin A, an 18-residue lasso peptide encoded by the five-gene cluster larABCDE, displays potent and selective anti-mycobacterial activity. The structural feature is an N-terminal macrolactam ring, through which the C-terminal passed to form the rigid lariat-protoknot structure. In the present study, we established a convergent expression system by the strategy in which larA mutant gene-carrying plasmids were transformed into larA-deficient Rhodococcus jostii and generated 36 lariatin variants of the precursor protein LarA to investigate the biosynthesis and the structure-activity relationships. The mutational analysis revealed that four amino acid residues (Gly1, Arg7, Glu8 and Trp9) in lariatin A are essential for the maturation and production in the biosynthetic machinery. Furthermore, the study on structure-activity relationships demonstrated that Tyr6, Gly11 and Asn14 are responsible for the anti-mycobacterial activity and the residues at positions 15, 16 and 18 in lariatin A are critical for enhancing the activity. This study will not only provide a useful platform for genetically engineering Gram-positive bacterium-producing lasso peptides, but also an important foundation to rationally design more promising drug candidates for combatting tuberculosis.
Using CRISPR-Cas9 to quantify the contributions of O-glycans, N-glycans and Glycosphingolipids to human leukocyte-endothelium adhesion
Authors: Stolfa Gino , Mondal Nandini , Zhu Yuqi , Yu Xinheng , Buffone Alexander , Neelamegham Sriram 
Published: July 2016

AbstractThere is often interest in dissecting the relative contributions of the N-glycans, O-glycans and glycosphingolipids (GSLs) in regulating complex biological traits like cell signaling, adhesion, development and metastasis. To address this, we developed a CRISPR-Cas9 toolkit to selectively truncate each of these commonly expressed glycan-types. Here, O-glycan biosynthesis was truncated by knocking-out Core 1 β3Gal-T Specific Molecular Chaperone (COSMC), N-glycans by targeting the β1,2 GlcNAc-transferase (MGAT1) and GSLs by deleting UDP-glucose ceramide glucosyltransferase (UGCG). These reagents were applied to reveal the glycoconjugates regulating human myeloid cell adhesion to selectins under physiological shear-flow observed during inflammation. These functional studies show that leukocyte rolling on P- and L-selectin is ablated in cells lacking O-glycans, with N-glycan truncation also increasing cell rolling velocity on L-selectin. All three glycan families contributed to E-selectin dependent cell adhesion with N-glycans contributing to all aspects of the leukocyte adhesion cascade, O-glycans only being important during initial recruitment and GSLs stabilizing slow cell rolling and the transition to firm arrest. Overall, the genome editing tools developed here may be broadly applied in studies of cellular glycosylation.
Context-specific protection of TGFα null mice from osteoarthritis
Authors: Usmani Shirine E. , Ulici Veronica , Pest Michael A. , Hill Tracy L. , Welch Ian D. , Beier Frank 
Published: July 2016

AbstractTransforming growth factor alpha (TGFα) is a growth factor involved in osteoarthritis (OA). TGFα induces an OA-like phenotype in articular chondrocytes, by inhibiting matrix synthesis and promoting catabolic factor expression. To better understand TGFα’s potential as a therapeutic target, we employed two in vivo OA models: (1) post-traumatic and (2) aging related OA. Ten-week old and six-month old male Tgfa null mice and their heterozygous (control) littermates underwent destabilization of the medial meniscus (DMM) surgery. Disease progression was assessed histologically using the Osteoarthritis Research Society International (OARSI) scoring system. As well, spontaneous disease progression was analyzed in eighteen-month-old Tgfa null and heterozygous mice. Ten-week old Tgfa null mice were protected from OA progression at both seven and fourteen weeks post-surgery. No protection was seen however in six-month old null mice after DMM surgery and no differences were observed between genotypes in the aging model. Thus, young Tgfa null mice are protected from OA progression in the DMM model, while older mice are not. In addition, Tgfa null mice are equally susceptible to spontaneous OA development during aging. Thus, TGFα might be a valuable therapeutic target in some post-traumatic forms of OA, however its role in idiopathic disease is less clear.
Coherent optical phonon oscillation and possible electronic softening in WTe2 crystals
Authors: He Bin , Zhang Chunfeng , Zhu Weida , Li Yufeng , Liu Shenghua , Zhu Xiyu , Wu Xuewei , Wang Xiaoyong , Wen Hai-hu , Xiao Min 
Published: July 2016

AbstractA rapidly-growing interest in WTe2 has been triggered by the giant magnetoresistance effect discovered in this unique system. While many efforts have been made towards uncovering the electron- and spin-relevant mechanisms, the role of lattice vibration remains poorly understood. Here, we study the coherent vibrational dynamics in WTe2 crystals by using ultrafast pump-probe spectroscopy. The oscillation signal in time domain in WTe2 has been ascribed as due to the coherent dynamics of the lowest energy A1 optical phonons with polarization- and wavelength-dependent measurements. With increasing temperature, the phonon energy decreases due to anharmonic decay of the optical phonons into acoustic phonons. Moreover, a significant drop (15%) of the phonon energy with increasing pump power is observed which is possibly caused by the lattice anharmonicity induced by electronic excitation and phonon-phonon interaction.
Localized recovery of complex networks against failure
Authors: Shang Yilun 
Published: July 2016

AbstractResilience of complex networks to failure has been an important issue in network research for decades and recent studies have begun to focus on the inverse recovery of network functionality through strategically healing missing nodes or edges. However, the effect of network recovery is far from fully understood and a general theory is still missing. Here we propose and study a general model of localized recovery, where a group of neighboring nodes are restored in an invasive way from a seed node. We develop a theoretical framework to compare the effect of random recovery (RR) and localized recovery (LR) in complex networks including Erdős-Rényi networks, random regular networks and scale-free networks. We find detailed phase diagrams for the subnetwork of occupied nodes and the “complement network” of failed nodes under RR and LR. By identifying the two competitive forces behind LR, we present an analytical and numerical approach to guide us in choosing the appropriate recovery strategy and provide estimation on its effect by using the degree distribution of the original network as the only input. Our work therefore provides insight for quantitatively understanding recovery process and its implications in infrastructure protection in various complex systems.
MoS2-clad microfibre laser delivering conventional, dispersion-managed and dissipative solitons
Authors: Cui Yudong , Lu Feifei , Liu Xueming 
Published: July 2016

AbstractMolybdenum disulfide (MoS2), whose monolayer possesses a direct band gap, displays promising applications in optoelectronics, photonics, and lasers. Recent researches have demonstrated that MoS2 has not only a significant broadband saturable absorption performance, but also a higher optical nonlinear response than graphene. However, MoS2 shows much lower optical damage threshold owing to the poorer thermal conductivity and mechanical property. Here, we exploit a MoS2-clad microfibre (MCM) as the saturable absorber (SA) for the generation of ultrashort pulses under different dispersion conditions. The improved evanescent field interaction scheme can overcome the laser-induced thermal damage, as well as take full advantage of the strong nonlinear effect of MoS2. With the MCM SA, conventional, dispersion-managed, and dissipative solitons are generated around 1600 nm in Er-doped fibre lasers with anomalous, near-zero, and normal cavity dispersions, respectively. Our work paves the way for applications of 2D layered materials in photonics, especially in laser sources.
Design and implementation of a high‐performance technique for tracking PV peak power
Authors: Belkaid Abdelhakim , Gaubert Jean‐Paul , Gherbi Ahmed 
Published: July 2016

Most maximum power point tracking (MPPT) techniques based on sliding‐mode control (SMC) use another method such as perturb and observe or incremental conductance (IncCond) to provide current or voltage reference which makes the system more complex. To reduce the complexity and to increase the photovoltaic (PV) array efficiency, a direct control high‐performance MPPT based on improved SMC has been investigated in this study. Using two different step sizes can follow the PV peak power at different operating conditions with rapid convergence and greater accuracy. The new SMC‐based MPPT designed for boost‐type DC/DC converters is compared with a conventional and modified IncCond method, and to a classical SMC method which is very similar to that applied by Chu et al. The proposed PV‐MPPT system is tested during a stringent profile of sunshine variation as recommended by the European Norm 50530, by simulation within MATLAB/SimulinkTM tools and verified by implementation using a test bench based on DS1104 R&D controller board. The obtained results are satisfactory and demonstrate that the new SMC can track the MPP quickly within 0.003 s and with good accuracy close to 99%.
Early-life disease exposure and associations with adult survival, cause of death, and reproductive success in preindustrial humans
Authors: Hayward Adam D. , Rigby Francesca L. , Lummaa Virpi 
Published: July 2016

Significance
Why has human life expectancy increased since 1850? A leading hypothesis proposes that limited exposure to childhood infections has reduced lifelong inflammation and enhanced survival, but tests of this hypothesis typically use all-cause mortality rates to estimate disease exposure. Meanwhile, links between early-life disease and reproduction have been neglected. We used data from preindustrial Finnish populations to show that early-life disease exposure was not associated with all-cause mortality, mortality from cardiovascular disease, stroke, and cancer, or reproductive success. Our study therefore does not support the prevailing contention that reduced exposure to early-life infections has increased life expectancy in modern populations.
Earth’s oxygen cycle and the evolution of animal life
Authors: Reinhard Christopher T. , Planavsky Noah J. , Olson Stephanie L. , Lyons Timothy W. , Erwin Douglas H. 
Published: July 2016

Significance
Earth is currently the only planet known to harbor complex life. Understanding whether terrestrial biotic complexity is a unique phenomenon or can be expected to be widespread in the universe depends on a mechanistic understanding of the factors that led to the emergence of complex life on Earth. Here, we use geochemical constraints and quantitative models to suggest that marine environments may have been unfavorable for the emergence and large-scale proliferation of motile multicellular life for most of Earth’s history. Further, we argue that a holistic evaluation of environmental variability, organismal life history, and spatial ecological dynamics is essential for a full accounting of the factors that have allowed for the emergence of biological complexity on Earth.
Flight paths of seabirds soaring over the ocean surface enable measurement of fine-scale wind speed and direction
Authors: Yonehara Yoshinari , Goto Yusuke , Yoda Ken , Watanuki Yutaka , Young Lindsay C. , Weimerskirch Henri , Bost Charles-André , Sato Katsufumi 
Published: July 2016

Significance
Monitoring ocean surface winds is essential for understanding ocean and atmosphere interactions and weather forecasts. However, wind measured by satellite scatterometers and buoys are spatially and temporally coarse, particularly in coastal areas. We deployed small global positioning system units on soaring seabirds to record their tracks. Seabirds were accelerated by tail winds or slowed down by head winds during flight, so their flight speed changed in relation to wind speed and direction. Taking advantage of these changes in flight speed, we reliably estimated wind speed and direction experienced by the seabirds. The wind observed by soaring seabird’s tracks complemented the conventional observation gaps in terms of both time and space, suggesting the possibility of using soaring seabirds as a living anemometer.
The neural chaperone proSAAS blocks α-synuclein fibrillation and neurotoxicity
Authors: Jarvela Timothy S. , Lam Hoa A. , Helwig Michael , Lorenzen Nikolai , Otzen Daniel E. , McLean Pamela J. , Maidment Nigel T. , Lindberg Iris 
Published: July 2016

SignificanceAberrant protein homeostasis (proteostasis) is increasingly recognized as a major causal factor in the development of protein aggregates, including aggregation of α-synuclein in Parkinson’s disease. Cellular proteins known as chaperones control proteostatic processes and are strongly associated with many different neurodegenerative diseases. We show here that an abundant brain- and endocrine-specific secretory chaperone known as proSAAS (named after four residues in the amino terminal region) exhibits potent antiaggregant effects on α-synuclein aggregation, and we identify a region of the protein that is necessary for this antiaggregant effect. We further show that proSAAS expression is able to stop α-synuclein from killing dopaminergic cells in a nigral cell model of Parkinson’s disease. This work demonstrates an important role for the proSAAS protein in blocking aggregation in neurodegeneration.
Stress and corticosteroids regulate rat hippocampal mitochondrial DNA gene expression via the glucocorticoid receptor
Authors: Hunter Richard G. , Seligsohn Ma’ayan , Rubin Todd G. , Griffiths Brian B. , Ozdemir Yildirim , Pfaff Donald W. , Datson Nicole A. , McEwen Bruce S. 
Published: July 2016

Significance
Successful response to stress requires that an organism rapidly direct its energy toward an appropriate survival response. The brain is central to successful survival decisions, and therefore its ability to allocate energetic resources precisely in response to stress is paramount. Glucocorticoid stress hormones have long been known to assist in the liberation of energy during stress via their ability to regulate the activity of the nuclear genome. The cellular powerhouse, the mitochondria, also contains a genome; herein we show that glucocorticoids, acting through their receptors, regulate the expression of mitochondrial genes in the brain. These findings demonstrate a direct molecular linkage between stress and mitochondrial function.
Highly sensitive detection of influenza virus by boron-doped diamond electrode terminated with sialic acid-mimic peptide
Authors: Matsubara Teruhiko , Ujie Michiko , Yamamoto Takashi , Akahori Miku , Einaga Yasuaki , Sato Toshinori 
Published: July 2016

Significance
A large number of people suffer from influenza every year. Early detection is critical for preventing severe influenza in high-risk groups. There is usually not enough time to produce vaccines against pandemic viruses before they spread to other countries. Anti-influenza therapy using neuraminidase inhibitors is effective within 30 h of the onset of symptoms. Here we show that several dozen plaque-forming units of influenza virus (IFV) are detectable by a boron-doped diamond electrode terminated with a sialic acid-mimic peptide with the ability to capture IFV. The electrode was sufficiently sensitive to detect IFV in specimens obtained in the early phase of infection. The device developed in the present work has potential applications in the highly sensitive detection of IFV to fight against influenza.
Complete in vitro generation of fertile oocytes from mouse primordial germ cells
Authors: Morohaku Kanako , Tanimoto Ren , Sasaki Keisuke , Kawahara-Miki Ryouka , Kono Tomohiro , Hayashi Katsuhiko , Hirao Yuji , Obata Yayoi 
Published: July 2016

Significance
Throughout the life of female mammals, only a small number of viable oocytes are produced. The mechanisms underlying the creation and selection of competent oocytes remain unclear. Here, we propose a novel approach for elucidating these unsolved questions, involving the use of an in vitro system established in the present study, which can fully reproduce mammalian oogenesis from mouse fetal primordial germ cells. Reconstitution of the entire oogenesis process has not been previously accomplished. Our system will assist in understanding the mechanisms of oogenesis and also create a new gamete resource in mammals.
Menopause accelerates biological aging
Authors: Levine Morgan E. , Lu Ake T. , Chen Brian H. , Hernandez Dena G. , Singleton Andrew B. , Ferrucci Luigi , Bandinelli Stefania , Salfati Elias , Manson JoAnn E. , Quach Austin , Kusters Cynthia D. J. , Kuh Diana , Wong Andrew , Teschendorff Andrew E. , Widschwendter Martin , Ritz Beate R. , Absher Devin , Assimes Themistocles L. , Horvath Steve 
Published: July 2016

Significance
Within an evolutionary framework, aging and reproduction are intrinsically linked. Although both laboratory and epidemiological studies have observed associations between the timing of reproductive senescence and longevity, it is not yet known whether differences in the age of menopause are reflected in biomarkers of aging. Using our recently developed biomarker of aging, the “epigenetic clock,” we examined whether age at menopause is associated with epigenetic age of blood, saliva, and buccal epithelium. This is a definitive study that shows an association between age of menopause and biological aging (measured using the epigenetic clock). Our results also indicate menopause may accelerate the epigenetic aging process in blood and that age at menopause and epigenetic age acceleration share a common genetic signature.
On the origin and evolutionary consequences of gene body DNA methylation
Authors: Bewick Adam J. , Ji Lexiang , Niederhuth Chad E. , Willing Eva-Maria , Hofmeister Brigitte T. , Shi Xiuling , Wang Li , Lu Zefu , Rohr Nicholas A. , Hartwig Benjamin , Kiefer Christiane , Deal Roger B. , Schmutz Jeremy , Grimwood Jane , Stroud Hume , Jacobsen Steven E. , Schneeberger Korbinian , Zhang Xiaoyu , Schmitz Robert J. 
Published: July 2016

SignificanceDNA methylation in plants is found at CG, CHG, and CHH sequence contexts. In plants, CG DNA methylation is enriched in the transcribed regions of many constitutively expressed genes (gene body methylation; gbM) and shows correlations with several chromatin modifications. Contrary to other types of DNA methylation, the evolution and function of gbM are largely unknown. Here we show two independent concomitant losses of the DNA methyltransferase CHROMOMETHYLASE 3 (CMT3) and gbM without the predicted disruption of transcription and of modifications to chromatin. This result suggests that CMT3 is required for the establishment of gbM in actively transcribed genes, and that gbM is dispensable for normal transcription as well as for the composition and modification of plant chromatin.
Chromosomal landscape of UV damage formation and repair at single-nucleotide resolution
Authors: Mao Peng , Smerdon Michael J. , Roberts Steven A. , Wyrick John J. 
Published: July 2016

Significance
UV-induced DNA lesions are an important contributor to melanomas and other skin cancers. To understand how UV damage leads to cancer-associated mutations, it is important to know how the chromosomal landscape influences initial UV damage formation and repair. We have developed a UV damage mapping procedure to precisely map UV damage throughout the genome. We used this method to map the genome-wide distribution of UV lesions in yeast, a model eukaryote. We found that UV damage is not uniformly distributed, but that damage formation is significantly modulated in a predictable way by nucleosomes and DNA-bound transcription factors. Additionally, genome-wide analysis of removal of UV lesions indicates that repair is significantly inhibited near the center of strongly positioned nucleosomes.
Computational investigation of cold denaturation in the Trp-cage miniprotein
Authors: Kim Sang Beom , Palmer Jeremy C. , Debenedetti Pablo G. 
Published: July 2016

Significance
The ubiquity of cold denaturation in globular proteins has broad implications for developing preservation strategies for biological materials and understanding the evolution of freeze-tolerant organisms. Because cold denaturation conditions typically lie below water’s freezing point, direct experimental investigation of this phenomenon is often frustrated by ice formation in the surrounding solvent. Coarse-grained lattice and off-lattice models have provided significant insight into protein cold denaturation, but they lack the structural resolution to fully elucidate the molecular mechanism involved in this process. We perform extensive replica exchange molecular dynamics simulations (324 μs total) to conduct a fully atomistic computational study of cold unfolding of an α-helical protein.
The enigma of the apparent disappearance of Eurasian highly pathogenic H5 clade 2.3.4.4 influenza A viruses in North American waterfowl
Authors: Krauss Scott , Stallknecht David E. , Slemons Richard D. , Bowman Andrew S. , Poulson Rebecca L. , Nolting Jacqueline M. , Knowles James P. , Webster Robert G. 
Published: July 2016

Significance
The role of wild aquatic birds in perpetuating highly pathogenic avian influenza viruses (HPAIVs) is unresolved. We examined whether the subtype H5 clade 2.3.4.4 HPAIV that devastated the US poultry industry in 2015 is perpetuated in wild aquatic birds. Virologic surveillance in 2014/15 and over the previous 43 y failed to detect HPAIVs in wild aquatic birds before or after the poultry outbreak, supporting the premise that there are unresolved mechanisms preventing wild aquatic birds from perpetuating HPAIVs. The significance of these findings is that timely and efficient strategies used to successfully prevent and eradicate HPAIVs infecting poultry, without the use of vaccines, appear to complement natural biological mechanisms in disrupting the perpetuation and possible spread of HPAIVs by wild aquatic birds.