bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis of a burkholdine analogue containing β-hydroxytyrosine
Authors: Kato Seiya , Sasaki Mio , Yano Shigekazu , Konno Hiroyuki 
Published: March 2019

ABSTRACT
Synthesis of a β-OHTyr-containing Bk analogue, a cyclic octalipopeptide with antifungal activities, is described. Since β-OHTyr-containing peptides generally are unstable in strong acidic conditions, synthesis of β-HOTyr-containing peptides by SPPS have rarely been reported. To overcome this problem, we found that using distilled TFA removed the protecting groups of side chains of β-OHTyr-containing Bk analogue, which was prepared by Fmoc-SPPS.
Abbreviations: β-OHTyr: β-hydroxytyrosine; β-OHAsn: β-hydroxyasparagine; Bk: burkholdine; FAA: fatty acyl amino acid; β-MeOTyr: β-methoxytyrosine; SPPS: solid phase peptide synthesis; MIC: minimun inhibitory concentration; DMF: dimethyl formamide; DIPEA: diisopropylethylamine; DIPC: diisopropylcarbodiimide; HOBt: 1-hydroxybenzotriazole; Fmoc: 9-fluorenylmethyloxycarbonyl; HFIP: 1,1,1,3,3,3-hexafluoropropan-2-ol; TFA: trifluoroacetic acid; LAP: N-lauryl −3-amino-4-carbamolypropanoic acid; HPLC: high performance liquid chromatography; ESI-TOFMS: electrospray ionization-time of flight mass spectrometry; Bn: benzyl; Boc: t-butyloxycatbonyl; 2-CTC: 2-chlorotritylchloride.
LncRNA CASC11 improves atherosclerosis by downregulating IL-9 and regulating vascular smooth muscle cell apoptosis and proliferation
Authors: Tao Kaiyu , Hu Zhanglong , Zhang Yigong , Jiang Daming , Cheng Haifeng 
Published: March 2019

ABSTRACT
LncRNA CASC11 is an oncogene in several types of cancer, while its role in atherosclerosis is unknown. In the present study we found that CASC11 was downregulated, while IL-9 was upregulated in plasma of atherosclerosis patients compared with healthy controls. Altered plasma levels of CASC11 and IL-9 distinguished atherosclerosis patients from healthy controls. CASC11 and IL-9 were significantly and inversely correlated in atherosclerosis patients but not in healthy controls. Exogenous IL-9 treatment failed to significantly affect expression levels of CASC11 in vascular smooth muscle cells (VSMC), while CASC11 overexpression resulted in the downregulation of IL-9. CASC11 overexpression also resulted in the downregulation of proliferation and promoted apoptosis of VSMC. Therefore, CASC11 may improve atherosclerosis by downregulating IL-9 and regulating VSMC apoptosis and proliferation.
Codifference can detect ergodicity breaking and non-Gaussianity
Authors: Ślęzak Jakub , Metzler Ralf , Magdziarz Marcin 
Published: March 2019

Abstract
We show that the codifference is a useful tool in studying the ergodicity breaking and non-Gaussianity properties of stochastic time series. While the codifference is a measure of dependence that was previously studied mainly in the context of stable processes, we here extend its range of applicability to random-parameter and diffusing-diffusivity models which are important in contemporary physics, biology and financial engineering. We prove that the codifference detects forms of dependence and ergodicity breaking which are not visible from analysing the covariance and correlation functions. We also discuss a related measure of dispersion, which is a nonlinear analogue of the mean squared displacement.
The NOMAD laboratory: from data sharing to artificial intelligence
Authors: Draxl Claudia , Scheffler Matthias 
Published: March 2019

Abstract
The Novel Materials Discovery (NOMAD) Laboratory is a user-driven platform for sharing and exploiting computational materials science data. It accounts for the various aspects of data being a crucial raw material and most relevant to accelerate materials research and engineering. NOMAD, with the NOMAD Repository, and its code-independent and normalized form, the NOMAD Archive, comprises the worldwide largest data collection of this field. Based on its findable accessible, interoperable, reusable data infrastructure, various services are offered, comprising advanced visualization, the NOMAD Encyclopedia, and artificial-intelligence tools. The latter are realized in the NOMAD Analytics Toolkit. Prerequisite for all this is the NOMAD metadata, a unique and thorough description of the data, that are produced by all important computer codes of the community. Uploaded data are tagged by a persistent identifier, and users can also request a digital object identifier to make data citable. Developments and advancements of parsers and metadata are organized jointly with users and code developers. In this work, we review the NOMAD concept and implementation, highlight its orthogonality to and synergistic interplay with other data collections, and provide an outlook regarding ongoing and future developments.
rMTA: robust metabolic transformation analysis
Authors: Valcárcel Luis V , Torrano Verónica , Tobalina Luis , Carracedo Arkaitz , Planes Francisco J 
Published: March 2019

Abstract

Motivation
The development of computational tools exploiting -omics data and high-quality genome-scale metabolic networks for the identification of novel drug targets is a relevant topic in Systems Medicine. Metabolic Transformation Algorithm (MTA) is one of these tools, which aims to identify targets that transform a disease metabolic state back into a healthy state, with potential application in any disease where a clear metabolic alteration is observed.

Results
Here, we present a robust extension to MTA (rMTA), which additionally incorporates a worst-case scenario analysis and minimization of metabolic adjustment to evaluate the beneficial effect of gene knockouts. We show that rMTA complements MTA in the different datasets analyzed (gene knockout perturbations in different organisms, Alzheimer’s disease and prostate cancer), bringing a more accurate tool for predicting therapeutic targets.

Availability and implementation
rMTA is freely available on The Cobra Toolbox: https://opencobra.github.io/cobratoolbox/latest/.

Supplementary information
Supplementary data are available at Bioinformatics online.
Shouji: a fast and efficient pre-alignment filter for sequence alignment
Authors: Alser Mohammed , Hassan Hasan , Kumar Akash , Mutlu Onur , Alkan Can 
Published: March 2019

Abstract

Motivation
The ability to generate massive amounts of sequencing data continues to overwhelm the processing capability of existing algorithms and compute infrastructures. In this work, we explore the use of hardware/software co-design and hardware acceleration to significantly reduce the execution time of short sequence alignment, a crucial step in analyzing sequenced genomes. We introduce Shouji, a highly parallel and accurate pre-alignment filter that remarkably reduces the need for computationally-costly dynamic programming algorithms. The first key idea of our proposed pre-alignment filter is to provide high filtering accuracy by correctly detecting all common subsequences shared between two given sequences. The second key idea is to design a hardware accelerator that adopts modern field-programmable gate array (FPGA) architectures to further boost the performance of our algorithm.

Results
Shouji significantly improves the accuracy of pre-alignment filtering by up to two orders of magnitude compared to the state-of-the-art pre-alignment filters, GateKeeper and SHD. Our FPGA-based accelerator is up to three orders of magnitude faster than the equivalent CPU implementation of Shouji. Using a single FPGA chip, we benchmark the benefits of integrating Shouji with five state-of-the-art sequence aligners, designed for different computing platforms. The addition of Shouji as a pre-alignment step reduces the execution time of the five state-of-the-art sequence aligners by up to 18.8×. Shouji can be adapted for any bioinformatics pipeline that performs sequence alignment for verification. Unlike most existing methods that aim to accelerate sequence alignment, Shouji does not sacrifice any of the aligner capabilities, as it does not modify or replace the alignment step.

Availability and implementation
https://github.com/CMU-SAFARI/Shouji.

Supplementary information
Supplementary data are available at Bioinformatics online.
Identifying the distribution of Atlantic cod spawning using multiple fixed and glider-mounted acoustic technologies
Authors: Zemeckis Douglas R , Dean Micah J , DeAngelis Annamaria I , Van Parijs Sofie M , Hoffman William S , Baumgartner Mark F , Hatch Leila T , Cadrin Steven X , McGuire Christopher H 
Published: March 2019

Abstract
Effective fishery management measures to protect fish spawning aggregations require reliable information on the spatio-temporal distribution of spawning. Spawning closures have been part of a suite of fishery management actions to rebuild the Gulf of Maine stock of Atlantic cod (Gadus morhua), but difficulties remain with managing rebuilding. The objective of this study was to identify the spatial and temporal distribution of cod spawning during winter in Massachusetts Bay to improve our understanding of cod spawning dynamics and inform fisheries management. Spawning was investigated in collaboration with commercial fishermen during three winter spawning seasons (October 2013–March 2016) using acoustic telemetry and passive acoustic monitoring equipment deployed in fixed-station arrays and mounted on mobile autonomous gliders. Tagged cod exhibited spawning site fidelity and spawning primarily occurred from early November through January with a mid-December peak and some inter-annual variability. The spatial distribution of spawning was generally consistent among years with multiple hotspots in areas &gt;50 m depth. Current closures encompass most of spawning, but important areas are recommended for potential modifications. Utilizing multiple complementary technologies and deployment strategies in collaboration with commercial fishermen enabled a comprehensive description of spawning and provides a valuable model for future studies.
Antibacterial effect of imipenem/relebactam on aerobic Gram-negative bacilli: in vitro simulations of 7 or 14 day human exposures
Authors: Noel Alan R , Bowker Karen E , Attwood Marie , MacGowan Alasdair P 
Published: March 2019

Abstract

Objectives
We assessed the antibacterial effect of human simulations of dosing with imipenem/relebactam (with or without amikacin) on Enterobacteriaceae or Pseudomonas aeruginosa over 7 or 14 day antibiotic exposures.

Methods
An in vitro pharmacokinetic model was used to assess changes in bacterial load and population profiles.

Results
Imipenem/relebactam produced an initial >4 log drop in viable counts followed by suppression for 7 days for Enterobacteriaceae whether the strain was WT, produced KPC enzymes or produced an AmpC enzyme with porin loss. Similarly, with the P. aeruginosa strains, there was an initial >4 log clearance over the first 24 h irrespective of whether the strain was WT, hyperexpressed AmpC or had OprD mutation with porin loss. However, with three of four strains there was modest regrowth over the 7 days. There were no changes in imipenem/relebactam MICs over the 7 days. Addition of amikacin in 7 day simulations resulted in more suppression of pseudomonal growth. In 14 day simulations with P. aeruginosa there was regrowth to 8 log10 by 14 days with imipenem/relebactam alone and associated increases in MICs. Addition of amikacin resulted in clearance from the model and prevented changes in population profiles.

Conclusions
Imipenem/relebactam was highly effective at reducing the bacterial load of Enterobacteriaceae and there was no emergence of resistance. Against P. aeruginosa, the initial bacterial burden was also rapidly reduced, but there was subsequent regrowth, especially after 7 days of exposure. Addition of amikacin increased the clearance of P. aeruginosa and prevented emergence of resistance.
Improvements in Gulf War Illness Symptoms After Near-Infrared Transcranial and Intranasal Photobiomodulation: Two Case Reports
Authors: Chao Linda L 
Published: March 2019

Abstract
At least one-fourth of US veterans who served in the 1990–1991 Gulf War (GW) are affected by the chronic symptomatic illness known as Gulf War illness (GWI). This condition typically includes some combination of fatigue, headaches, cognitive dysfunction, musculoskeletal pain, and respiratory, gastrointestinal and dermatologic complaints. To date, effective treatments for GWI have been elusive. Photobiomodulation (PBM) describes the non-pharmacological, non-thermal use of light to stimulate, heal, and protect tissue that has either been injured, is degenerating, or else is at risk of dying. Significant benefits have been reported following application of transcranial PBM to humans with acute stoke, traumatic brain injury (TBI), and dementia. This report describes the first documentation of improved GWI symptoms in two GW veterans following 12 weeks of PBM treatments.
The time delay between star formation quenching and morphological transformation of galaxies in clusters: a phase–space view of EDisCS
Authors: Kelkar Kshitija , Gray Meghan E , Aragón-Salamanca Alfonso , Rudnick Gregory , Jaffé Yara L , Jablonka Pascale , Moustakas John , Milvang-Jensen Bo 
Published: March 2019

AbstractWe explore the possible effect of cluster environments on the structure and star formation histories of galaxies by analysing the projected phase–space (PPS) of intermediate-redshift clusters (0.4 ≤ z ≤ 0.8). HST I−band imaging data from the ESO Distant Cluster Survey (EDisCS) allow us to measure deviations of the galaxies’ light distributions from symmetric and smooth profiles using two parameters, Ares (‘asymmetry’) and RFF (residual flux fraction or ‘roughness’). Combining these structural parameters with age-sensitive spectral indicators ($H_{\delta \rm {A}}$, $H_{\gamma \rm {A}}$, and Dn4000), we establish that in all environments younger star-forming galaxies of all morphologies are ‘rougher’ and more asymmetric than older, more quiescent ones. Combining a subset of the EDisCS clusters, we construct a stacked PPS diagram and find a significant correlation between the position of the galaxies on the PPS and their stellar ages, irrespective of their morphology. We also observe an increasing fraction of galaxies with older stellar populations towards the cluster core, while the galaxies’ structural parameters (Ares and RFF) do not seem to segregate strongly with PPS. These results may imply that, under the possible influence of their immediate cluster environment, galaxies have their star formation suppressed earlier, while their structural transformation happens on a longer time-scale as they accumulate and age in the cluster cores.
Association of changes in bone mineral parameters with mortality in haemodialysis patients: insights from the ARO cohort
Authors: Lamina Claudia , Kronenberg Florian , Stenvinkel Peter , Froissart Marc , Forer Lukas , Schönherr Sebastian , Wheeler David C , Eckardt Kai-Uwe , Floege Jürgen 
Published: March 2019

Abstract

Background
There is little information in haemodialysis (HD) patients on whether temporal changes in serum calcium, phosphate or intact parathyroid hormone (iPTH) are associated with mortality.

Methods
We analysed associations of phosphate, total calcium and iPTH with all-cause and cardiovascular mortality in 8817 incident HD patients from the European second Analyzing Data, Recognizing Excellence and Optimizing Outcomes (AROii) cohort enrolled in 2007–09, which were prospectively followed for a median of 3 years, using time-dependent Cox proportional hazards models. We evaluated changes in risk over time depending on changes in phosphate, calcium or iPTH.

Results
The association of phosphate and iPTH with all-cause mortality was U-shaped, with the lowest risk ranges between 1.20 and 1.89 mmol/L for phosphate and between 239 and 710 ng/L for iPTH. For total calcium, the associations were J-shaped, with an increased risk for all-cause mortality at levels &gt;2.36 mmol/L. Lowest risk ranges for cardiovascular mortality did not change markedly for all three parameters. If iPTH was below the lowest risk range at baseline (iPTH &lt;239 ng/L), a subsequent increase in levels was associated with improved survival. For phosphate, an increase or decrease out of the lowest risk range was associated with increased mortality risk. For calcium, this was only the case when the values increased above the lowest risk range.

Conclusion
In the AROii cohort, the ranges of bone mineral biomarkers associated with the lowest mortality ranges were largely consistent with the current Kidney Disease: Improving Global Outcomes chronic kidney disease–mineral and bone disorder guideline recommendations. Allowing a suppressed iPTH to increase was associated with a lower mortality, whereas shifts of phosphate or calcium outside the lowest risk range increased mortality.
Integrating morphological and molecular taxonomy with the revised concept of Stelligeridae (Porifera: Demospongiae)
Authors: Morrow Christine , Cárdenas Paco , Boury-Esnault Nicole , Picton Bernard , McCormack Grace , Van Soest Rob , Collins Allen , Redmond Niamh , Maggs Christine , Sigwart Julia , Allcock Louise A 
Published: March 2019

Abstract
This study reinforces and extends the findings of previous molecular studies showing that there is a close relationship between species assigned to the sponge genera Halicnemia, Higginsia, Paratimea and Stelligera and that the family Heteroxyidae is polyphyletic. The present study has led to the description of one new species of Halicnemia and six new species of Paratimea, the resurrection of Halicnemia gallica and a better understanding of the characters uniting Stelligeridae. A new species of Heteroxya is also described. We demonstrate that many of the taxa assigned to Heteroxyidae are more closely related to other families, and we propose several changes to the classification of Heteroscleromorpha. Desmoxyidae is resurrected from synonymy and transferred to Poecilosclerida; Higginsia anfractuosa is transferred to Hymedesmiidae, and a new genus, Hooperia, is erected for its reception; Higginsia durissima is returned to Bubaris (Bubaridae); Higginsia fragilis is transferred to Spanioplon (Hymedesmiidae); Hemiasterella camelus is transferred to Paratimea; and Raspailia (Parasyringella) australiensis and Ceratopsion axiferum are transferred to Adreus (Hemiasterellidae).
Vagus Nerve Stimulation Attenuates Multiple Organ Dysfunction in Resuscitated Porcine Progressive Sepsis
Authors: Kohoutova Michaela , Horak Jan , Jarkovska Dagmar , Martinkova Vendula , Tegl Vaclav , Nalos Lukas , Vistejnova Lucie , Benes Jan , Sviglerova Jitka , Kuncova Jitka , Matejovic Martin , Stengl Milan 
Published: March 2019

Objectives:
To investigate the potential benefits of vagus nerve stimulation in a clinically-relevant large animal model of progressive sepsis.

Design:
Prospective, controlled, randomized trial.

Setting:
University animal research laboratory.

Subjects:
Twenty-five domestic pigs were divided into three groups: 1) sepsis group (eight pigs), 2) sepsis + vagus nerve stimulation group (nine pigs), and 3) control sham group (eight pigs).

Interventions:
Sepsis was induced by cultivated autologous feces inoculation in anesthetized, mechanically ventilated, and surgically instrumented pigs and followed for 24 hours. Electrical stimulation of the cervical vagus nerve was initiated 6 hours after the induction of peritonitis and maintained throughout the experiment.

Measurements and Main Results:
Measurements of hemodynamics, electrocardiography, biochemistry, blood gases, cytokines, and blood cells were collected at baseline (just before peritonitis induction) and at the end of the in vivo experiment (24 hr after peritonitis induction). Subsequent in vitro analyses addressed cardiac contractility and calcium handling in isolated tissues and myocytes and analyzed mitochondrial function by ultrasensitive oxygraphy. Vagus nerve stimulation partially or completely prevented the development of hyperlactatemia, hyperdynamic circulation, cellular myocardial depression, shift in sympathovagal balance toward sympathetic dominance, and cardiac mitochondrial dysfunction, and reduced the number of activated monocytes. Sequential Organ Failure Assessment scores and vasopressor requirements significantly decreased after vagus nerve stimulation.

Conclusions:
In a clinically-relevant large animal model of progressive sepsis, vagus nerve stimulation was associated with a number of beneficial effects that resulted in significantly attenuated multiple organ dysfunction and reduced vasopressor and fluid resuscitation requirements. This suggests that vagus nerve stimulation might provide a significant therapeutic potential that warrants further thorough investigation.
Two accessory proteins govern MmpL3 mycolic acid transport in mycobacteria
Authors: Fay Allison , Czudnochowski Nadine , Rock Jeremy , Johnson Jeffrey R. , Krogan Nevan J. , Rosenberg Oren , Glickman Michael S. 
Published: March 2019

AbstractMycolic acids are the signature lipid of mycobacteria and constitute an important physical component of the cell wall, a target of mycobacterial specific antibiotics, and a mediator of M. tuberculosis pathogenesis. Mycolic acids are synthesized in the cytoplasm and are thought to be transported to the cell wall as a trehalose ester by the MmpL3 transporter, an antibiotic target for M. tuberculosis. However, the mechanism by which mycolate synthesis is coupled to transport, and the full MmpL3 transport machinery, is unknown. Here we identify two new components of the MmpL3 transport machinery in mycobacteria. The protein encoded by MSMEG_0736/Rv0383c is essential for growth of M. smegmatis and M. tuberculosis, is anchored to the cytoplasmic membrane, physically interacts with and colocalizes with MmpL3 in growing cells, and is required for trehalose monomycolate transport to the cell wall. In light of these findings we propose Msmeg_0736/Rv0383c be named “TMM transport factor A”, TtfA. The protein encoded by MSMEG_5308 also interacts with the MmpL3 complex, but is nonessential for growth or TMM transport. However, MSMEG_5308 accumulates with inhibition of MmpL3 mediated TMM transport and stabilizes the MmpL3/TtfA complex, indicating that it stabilizes the transport system during stress. These studies identify two new components of the mycobacterial mycolate transport machinery, an emerging antibiotic target in M. tuberculosis.
The C-terminal domains SnRK2-box and ABA-box have a role in sugarcane SnRK2s auto-activation and activity
Authors: Righetto Germanna , Sriranganadane Dev , Halabelian Levon , Chiodi Carla G. , Elkins Jonathan M. , Massirer Katlin B. , Gileadi Opher , Menossi Marcelo , Couñago Rafael M. 
Published: March 2019

AbstractResistance to drought stress is fundamental to plant survival and development. Abscisic acid (ABA) is one of the major hormones involved in different types of abiotic and biotic stress responses. ABA intracellular signaling has been extensively explored in Arabidopsis thaliana and occurs via a phosphorylation cascade mediated by three related protein kinases, denominated SnRK2s (SNF1-related protein kinases). However, the role of ABA signaling and the biochemistry of SnRK2 in crop plants remains underexplored. Considering the importance of the ABA hormone in abiotic stress tolerance, here we investigated the regulatory mechanism of sugarcane SnRK2s - known as SAPKs (Stress/ABA-activated Protein Kinases). The crystal structure of ScSAPK10 revealed the characteristic SnRK2 family architecture, in which the regulatory SnRK2-box interacts with the kinase domain αC helix. To study sugarcane SnRK2 regulation, we produced a series of mutants for the protein regulatory domains SnRK2-box and ABA-box. Surprisingly, mutations in the SnRK2-box did not drastically affect sugarcane SnRK2 activity, in contrast to previous observations for the homologous proteins in Arabidopsis. Also, we found that the ABA-box might have a role in SnRK2 activation in the absence of PP2C phosphatase. Taken together, our results demonstrate that both C-terminal domains of sugarcane SnRK2 proteins play a fundamental role in protein activation and activity.