bluuebunny/crossref_metadata_2025_split huggingface dataset:
Total synthesis of feglymycin based on a linear/convergent hybrid approach using micro-flow amide bond formation
Authors: Fuse Shinichiro , Mifune Yuto , Nakamura Hiroyuki , Tanaka Hiroshi 
Published: November 2016

AbstractFeglymycin is a naturally occurring, anti-HIV and antimicrobial 13-mer peptide that includes highly racemizable 3,5-dihydroxyphenylglycines (Dpgs). Here we describe the total synthesis of feglymycin based on a linear/convergent hybrid approach. Our originally developed micro-flow amide bond formation enabled highly racemizable peptide chain elongation based on a linear approach that was previously considered impossible. Our developed approach will enable the practical preparation of biologically active oligopeptides that contain highly racemizable amino acids, which are attractive drug candidates.
Amplification of USP13 drives ovarian cancer metabolism
Authors: Han Cecil , Yang Lifeng , Choi Hyun Ho , Baddour Joelle , Achreja Abhinav , Liu Yunhua , Li Yujing , Li Jiada , Wan Guohui , Huang Cheng , Ji Guang , Zhang Xinna , Nagrath Deepak , Lu Xiongbin 
Published: November 2016

AbstractDysregulated energetic metabolism has been recently identified as a hallmark of cancer. Although mutations in metabolic enzymes hardwire metabolism to tumourigenesis, they are relatively infrequent in ovarian cancer. More often, cancer metabolism is re-engineered by altered abundance and activity of the metabolic enzymes. Here we identify ubiquitin-specific peptidase 13 (USP13) as a master regulator that drives ovarian cancer metabolism. USP13 specifically deubiquitinates and thus upregulates ATP citrate lyase and oxoglutarate dehydrogenase, two key enzymes that determine mitochondrial respiration, glutaminolysis and fatty acid synthesis. The USP13 gene is co-amplified with PIK3CA in 29.3% of high-grade serous ovarian cancers and its overexpression is significantly associated with poor clinical outcome. Inhibiting USP13 remarkably suppresses ovarian tumour progression and sensitizes tumour cells to the treatment of PI3K/AKT inhibitor. Our results reveal an important metabolism-centric role of USP13, which may lead to potential therapeutics targeting USP13 in ovarian cancers.
Modulation of mRNA and lncRNA expression dynamics by the Set2–Rpd3S pathway
Authors: Kim Ji Hyun , Lee Bo Bae , Oh Young Mi , Zhu Chenchen , Steinmetz Lars M. , Lee Yookyeong , Kim Wan Kyu , Lee Sung Bae , Buratowski Stephen , Kim TaeSoo 
Published: November 2016

AbstractH3K36 methylation by Set2 targets Rpd3S histone deacetylase to transcribed regions of mRNA genes, repressing internal cryptic promoters and slowing elongation. Here we explore the function of this pathway by analysing transcription in yeast undergoing a series of carbon source shifts. Approximately 80 mRNA genes show increased induction upon SET2 deletion. A majority of these promoters have overlapping lncRNA transcription that targets H3K36me3 and deacetylation by Rpd3S to the mRNA promoter. We previously reported a similar mechanism for H3K4me2-mediated repression via recruitment of the Set3C histone deacetylase. Here we show that the distance between an mRNA and overlapping lncRNA promoter determines whether Set2–Rpd3S or Set3C represses. This analysis also reveals many previously unreported cryptic ncRNAs induced by specific carbon sources, showing that cryptic promoters can be environmentally regulated. Therefore, in addition to repression of cryptic transcription and modulation of elongation, H3K36 methylation maintains optimal expression dynamics of many mRNAs and ncRNAs.
Selective suppression of antisense transcription by Set2-mediated H3K36 methylation
Authors: Venkatesh Swaminathan , Li Hua , Gogol Madelaine M. , Workman Jerry L. 
Published: November 2016

AbstractMaintenance of a regular chromatin structure over the coding regions of genes occurs co-transcriptionally via the ‘chromatin resetting’ pathway. One of the central players in this pathway is the histone methyltransferase Set2. Here we show that the loss of Set2 in yeast, Saccharomyces cerevisiae, results in transcription initiation of antisense RNAs embedded within body of protein-coding genes. These RNAs are distinct from the previously identified non-coding RNAs and cover 11% of the yeast genome. These RNA species have been named Set2-repressed antisense transcripts (SRATs) since the co-transcriptional addition of the H3K36 methyl mark by Set2 over their start sites results in their suppression. Interestingly, loss of chromatin resetting factor Set2 or the subsequent production of SRATs does not affect the abundance of the sense transcripts. This difference in transcriptional outcomes of overlapping transcripts due to a strand-independent addition of H3K36 methylation is a key regulatory feature of interleaved transcriptomes.
Direct evidence for microbial-derived soil organic matter formation and its ecophysiological controls
Authors: Kallenbach Cynthia M. , Frey Serita D. , Grandy A. Stuart 
Published: November 2016

AbstractSoil organic matter (SOM) and the carbon and nutrients therein drive fundamental submicron- to global-scale biogeochemical processes and influence carbon-climate feedbacks. Consensus is emerging that microbial materials are an important constituent of stable SOM, and new conceptual and quantitative SOM models are rapidly incorporating this view. However, direct evidence demonstrating that microbial residues account for the chemistry, stability and abundance of SOM is still lacking. Further, emerging models emphasize the stabilization of microbial-derived SOM by abiotic mechanisms, while the effects of microbial physiology on microbial residue production remain unclear. Here we provide the first direct evidence that soil microbes produce chemically diverse, stable SOM. We show that SOM accumulation is driven by distinct microbial communities more so than clay mineralogy, where microbial-derived SOM accumulation is greatest in soils with higher fungal abundances and more efficient microbial biomass production.
Wnt5a induces renal AQP2 expression by activating calcineurin signalling pathway
Authors: Ando Fumiaki , Sohara Eisei , Morimoto Tetsuji , Yui Naofumi , Nomura Naohiro , Kikuchi Eriko , Takahashi Daiei , Mori Takayasu , Vandewalle Alain , Rai Tatemitsu , Sasaki Sei , Kondo Yoshiaki , Uchida Shinichi 
Published: November 2016

AbstractHeritable nephrogenic diabetes insipidus (NDI) is characterized by defective urine concentration mechanisms in the kidney, which are mainly caused by loss-of-function mutations in the vasopressin type 2 receptor. For the treatment of heritable NDI, novel strategies that bypass the defective vasopressin type 2 receptor are required to activate the aquaporin-2 (AQP2) water channel. Here we show that Wnt5a regulates AQP2 protein expression, phosphorylation and trafficking, suggesting that Wnt5a is an endogenous ligand that can regulate AQP2 without the activation of the classic vasopressin/cAMP signalling pathway. Wnt5a successfully increases the apical membrane localization of AQP2 and urine osmolality in an NDI mouse model. We also demonstrate that calcineurin is a key regulator of Wnt5a-induced AQP2 activation without affecting intracellular cAMP level and PKA activity. The importance of calcineurin is further confirmed with its activator, arachidonic acid, which shows vasopressin-like effects underlining that calcineurin activators may be potential therapeutic targets for heritable NDI.
Somatic increase of CCT8 mimics proteostasis of human pluripotent stem cells and extends C. elegans lifespan
Authors: Noormohammadi Alireza , Khodakarami Amirabbas , Gutierrez-Garcia Ricardo , Lee Hyun Ju , Koyuncu Seda , König Tim , Schindler Christina , Saez Isabel , Fatima Azra , Dieterich Christoph , Vilchez David 
Published: November 2016

AbstractHuman embryonic stem cells can replicate indefinitely while maintaining their undifferentiated state and, therefore, are immortal in culture. This capacity may demand avoidance of any imbalance in protein homeostasis (proteostasis) that would otherwise compromise stem cell identity. Here we show that human pluripotent stem cells exhibit enhanced assembly of the TRiC/CCT complex, a chaperonin that facilitates the folding of 10% of the proteome. We find that ectopic expression of a single subunit (CCT8) is sufficient to increase TRiC/CCT assembly. Moreover, increased TRiC/CCT complex is required to avoid aggregation of mutant Huntingtin protein. We further show that increased expression of CCT8 in somatic tissues extendsCaenorhabditis eleganslifespan in a TRiC/CCT-dependent manner. Ectopic expression of CCT8 also ameliorates the age-associated demise of proteostasis and corrects proteostatic deficiencies in worm models of Huntington’s disease. Our results suggest proteostasis is a common principle that links organismal longevity with hESC immortality.
FOXK1 interaction with FHL2 promotes proliferation, invasion and metastasis in colorectal cancer
Authors: Wu M , Wang J , Tang W , Zhan X , Li Y , Peng Y , Huang X , Bai Y , Zhao J , Li A , Chen C , Chen Y , Peng H , Ren Y , Li G , Liu S , Wang J 
Published: November 2016

AbstractThe transcriptional factor Forkhead box k1 (FOXK1) is a member of the FOX family. The abnormal expression of FOXK1 may have an important role in tumour development. Our previous studies showed that four-and-a-half LIM protein 2 (FHL2) is a critical inducer of the epithelial-to-mesenchymal transition (EMT) and invasion. However, the molecular mechanism by which FOXK1 synergizes with FHL2 tumour proliferation, EMT and metastasis is not well defined. We evaluated that messenger RNA (mRNA) and protein expression levels by quantitative RT–PCR, western blot, immunofluorescence and immunohistochemistry (IHC) assays. The migration and invasive abilities of colorectal cancer (CRC) cells were evaluated using short hairpin RNA (shRNA)-mediated inhibition in vitro and in vivo. We showed that FOXK1 expression was upregulated in CRC compared with matched normal tissues. FOXK1 physically interacts with FHL2 in CRC. Moreover, higher expression levels of the two proteins were significantly associated with differentiation, lymph node metastasis, AJCC stage and poorer prognosis. Furthermore, the overexpression of FOXK1 in CRC cells is associated with EMT, invasion and metastasis. However, the siRNA-mediated repression of FHL2 in FOXK1-overexpressing cells reversed EMT and both the proliferative and metastatic phenotypes in vitro and in vivo. These data identified that the co-expression of FOXK1 and FHL2 enhances cell proliferation and metastasis through the induction of EMT. Thus, FOXK1 and FHL2 may serve as putative targets in the combined therapy of CRC.
Combining Multiple Hypothesis Testing with Machine Learning Increases the Statistical Power of Genome-wide Association Studies
Authors: Mieth Bettina , Kloft Marius , Rodríguez Juan Antonio , Sonnenburg Sören , Vobruba Robin , Morcillo-Suárez Carlos , Farré Xavier , Marigorta Urko M. , Fehr Ernst , Dickhaus Thorsten , Blanchard Gilles , Schunk Daniel , Navarro Arcadi , Müller Klaus-Robert 
Published: November 2016

AbstractThe standard approach to the analysis of genome-wide association studies (GWAS) is based on testing each position in the genome individually for statistical significance of its association with the phenotype under investigation. To improve the analysis of GWAS, we propose a combination of machine learning and statistical testing that takes correlation structures within the set of SNPs under investigation in a mathematically well-controlled manner into account. The novel two-step algorithm, COMBI, first trains a support vector machine to determine a subset of candidate SNPs and then performs hypothesis tests for these SNPs together with an adequate threshold correction. Applying COMBI to data from a WTCCC study (2007) and measuring performance as replication by independent GWAS published within the 2008–2015 period, we show that our method outperforms ordinary raw p-value thresholding as well as other state-of-the-art methods. COMBI presents higher power and precision than the examined alternatives while yielding fewer false (i.e. non-replicated) and more true (i.e. replicated) discoveries when its results are validated on later GWAS studies. More than 80% of the discoveries made by COMBI upon WTCCC data have been validated by independent studies. Implementations of the COMBI method are available as a part of the GWASpi toolbox 2.0.
The Perfect Glass Paradigm: Disordered Hyperuniform Glasses Down to Absolute Zero
Authors: Zhang G. , Stillinger F. H. , Torquato S. 
Published: November 2016

AbstractRapid cooling of liquids below a certain temperature range can result in a transition to glassy states. The traditional understanding of glasses includes their thermodynamic metastability with respect to crystals. However, here we present specific examples of interactions that eliminate the possibilities of crystalline and quasicrystalline phases, while creating mechanically stable amorphous glasses down to absolute zero temperature. We show that this can be accomplished by introducing a new ideal state of matter called a “perfect glass”. A perfect glass represents a soft-interaction analog of the maximally random jammed (MRJ) packings of hard particles. These latter states can be regarded as the epitome of a glass since they are out of equilibrium, maximally disordered, hyperuniform, mechanically rigid with infinite bulk and shear moduli, and can never crystallize due to configuration-space trapping. Our model perfect glass utilizes two-, three-, and four-body soft interactions while simultaneously retaining the salient attributes of the MRJ state. These models constitute a theoretical proof of concept for perfect glasses and broaden our fundamental understanding of glass physics. A novel feature of equilibrium systems of identical particles interacting with the perfect-glass potential at positive temperature is that they have a non-relativistic speed of sound that is infinite.
Vectorized magnetometer for space applications using electrical readout of atomic scale defects in silicon carbide
Authors: Cochrane Corey J. , Blacksberg Jordana , Anders Mark A. , Lenahan Patrick M. 
Published: November 2016

AbstractMagnetometers are essential for scientific investigation of planetary bodies and are therefore ubiquitous on missions in space. Fluxgate and optically pumped atomic gas based magnetometers are typically flown because of their proven performance, reliability, and ability to adhere to the strict requirements associated with space missions. However, their complexity, size, and cost prevent their applicability in smaller missions involving cubesats. Conventional solid-state based magnetometers pose a viable solution, though many are prone to radiation damage and plagued with temperature instabilities. In this work, we report on the development of a new self-calibrating, solid-state based magnetometer which measures magnetic field induced changes in current within a SiC pn junction caused by the interaction of external magnetic fields with the atomic scale defects intrinsic to the semiconductor. Unlike heritage designs, the magnetometer does not require inductive sensing elements, high frequency radio, and/or optical circuitry and can be made significantly more compact and lightweight, thus enabling missions leveraging swarms of cubesats capable of science returns not possible with a single large-scale satellite. Additionally, the robustness of the SiC semiconductor allows for operation in extreme conditions such as the hot Venusian surface and the high radiation environment of the Jovian system.
SARS-CoV fusion peptides induce membrane surface ordering and curvature
Authors: Basso Luis G. M. , Vicente Eduardo F. , Crusca Edson , Cilli Eduardo M. , Costa-Filho Antonio J. 
Published: November 2016

AbstractViral membrane fusion is an orchestrated process triggered by membrane-anchored viral fusion glycoproteins. The S2 subunit of the spike glycoprotein from severe acute respiratory syndrome (SARS) coronavirus (CoV) contains internal domains called fusion peptides (FP) that play essential roles in virus entry. Although membrane fusion has been broadly studied, there are still major gaps in the molecular details of lipid rearrangements in the bilayer during fusion peptide-membrane interactions. Here we employed differential scanning calorimetry (DSC) and electron spin resonance (ESR) to gather information on the membrane fusion mechanism promoted by two putative SARS FPs. DSC data showed the peptides strongly perturb the structural integrity of anionic vesicles and support the hypothesis that the peptides generate opposing curvature stresses on phosphatidylethanolamine membranes. ESR showed that both FPs increase lipid packing and head group ordering as well as reduce the intramembrane water content for anionic membranes. Therefore, bending moment in the bilayer could be generated, promoting negative curvature. The significance of the ordering effect, membrane dehydration, changes in the curvature properties and the possible role of negatively charged phospholipids in helping to overcome the high kinetic barrier involved in the different stages of the SARS-CoV-mediated membrane fusion are discussed.
Brain microbiota disruption within inflammatory demyelinating lesions in multiple sclerosis
Authors: Branton W. G. , Lu J. Q. , Surette M. G. , Holt R. A. , Lind J. , Laman J. D. , Power C. 
Published: November 2016

AbstractMicrobial communities reside in healthy tissues but are often disrupted during disease. Bacterial genomes and proteins are detected in brains from humans, nonhuman primates, rodents and other species in the absence of neurological disease. We investigated the composition and abundance of microbiota in frozen and fixed autopsied brain samples from patients with multiple sclerosis (MS) and age- and sex-matched nonMS patients as controls, using neuropathological, molecular and bioinformatics tools. 16s rRNA sequencing revealed Proteobacteria to be the dominant phylum with restricted diversity in cerebral white matter (WM) from MS compared to nonMS patients. Both clinical groups displayed 1,200–1,400 bacterial genomes/cm3 and low bacterial rRNA:rDNA ratios in WM. RNAseq analyses showed a predominance of Proteobacteria in progressive MS patients’ WM, associated with increased inflammatory gene expression, relative to a broader range of bacterial phyla in relapsing-remitting MS patients’ WM. Although bacterial peptidoglycan (PGN) and RNA polymerase beta subunit immunoreactivities were observed in all patients, PGN immunodetection was correlated with demyelination and neuroinflammation in MS brains. Principal component analysis revealed that demyelination, PGN and inflammatory gene expression accounted for 86% of the observed variance. Thus, inflammatory demyelination is linked to an organ-specific dysbiosis in MS that could contribute to underlying disease mechanisms.
A novel bio-engineering approach to generate an eminent surface-functionalized template for selective detection of female sex pheromone of Helicoverpa armigera
Authors: Moitra Parikshit , Bhagat Deepa , Pratap Rudra , Bhattacharya Santanu 
Published: November 2016

AbstractPlant pests exert serious effects on food production due to which the global crop yields are reduced by ~20–40 percent per year. Hence to meet the world’s food needs, loses of food due to crop pests must be reduced. Herein the silicon dioxide based MEMS devices are covalently functionalized for robust and efficient optical sensing of the female sex pheromones of the pests like Helicoverpa armigera for the first time in literature. The functionalized devices are also capable of selectively measuring the concentration of this pheromone at femtogram level which is much below the concentration of pheromone at the time of pest infestation in an agricultural field. Experiments are also performed in a confined region in the presence of male and female pests and tomato plants which directly mimics the real environmental conditions. Again the reversible use and absolutely trouble free transportation of these pheromone nanosensors heightens their potentials for commercial use. Overall, a novel and unique approach for the selective and reversible sensing of female sex pheromones of certain hazardous pests is reported herein which may be efficiently and economically carried forward from the research laboratory to the agricultural field.
Evolution of cooperation under indirect reciprocity and arbitrary exploration rates
Authors: Santos Fernando P. , Pacheco Jorge M. , Santos Francisco C. 
Published: November 2016

AbstractCooperation has been recognized as an evolutionary puzzle since Darwin, and remains identified as one of the biggest challenges of the XXIst century. Indirect Reciprocity (IR), a key mechanism that humans employ to cooperate with each other, establishes that individual behaviour depends on reputations, which in turn evolve depending on social norms that classify behaviours as good or bad. While it is well known that different social norms give rise to distinct cooperation levels, it remains unclear how the performance of each norm is influenced by the random exploration of new behaviours, often a key component of social dynamics where a plethora of stimuli may compel individuals to deviate from pre-defined behaviours. Here we study, for the first time, the impact of varying degrees of exploration rates – the likelihood of spontaneously adopting another strategy, akin to a mutation probability in evolutionary dynamics – in the emergence of cooperation under IR. We show that high exploration rates may either improve or harm cooperation, depending on the underlying social norm at work. Regarding some of the most popular social norms studied to date, we find that cooperation under Simple-standing and Image-score is enhanced by high exploration rates, whereas the opposite occurs for Stern-judging and Shunning.
Narrowing the spread in CMIP5 model projections of air-sea CO2 fluxes
Authors: Wang Lei , Huang Jianbin , Luo Yong , Zhao Zongci 
Published: November 2016

AbstractLarge spread appears in the projection of air-sea CO2 fluxes using the latest simulations from the Coupled Model Intercomparison Project Phase 5 (CMIP5). Here, two methods are applied to narrow this spread in 13 CMIP5 models. One method involves model selection based on the ability of models to reproduce the observed air-sea CO2 fluxes from 1980 to 2005. The other method involves constrained estimation based on the strong relationship between the historical and future air-sea CO2 fluxes. The estimated spread of the projected air-sea CO2 fluxes is effectively reduced by using these two approaches. These two approaches also show great agreement in the global ocean and three regional oceans of the equatorial Pacific Ocean, the North Atlantic Ocean and the Southern Ocean, including the average state and evolution characteristics. Based on the projections of the two approaches, the global ocean carbon uptake will increase in the first half of the 21st century then remain relatively stable and is projected to be 3.68–4.57 PgC/yr at the end of 21st century. The projections indicate that the increase in the CO2 uptake by the oceans will cease at the year of approximately 2070.