bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computed Tomography–Guided Methylene Blue Labeling Prior to Thoracoscopic Resection of Small Deeply Placed Pulmonary Nodules. Do We Really Need Palpation?
Authors: Demiröz S. , Apaydın Selma , Ertürk Hakan , Biri Suzan , Incekara Funda , Aydogdu Koray , Kaya Sadi , Findik Gokturk 
Published: January 2017

Background Video-assisted thoracic surgery (VATS) is widely used for thoracic surgery operations, and day by day it becomes routine for the excision of undetermined pulmonary nodules. However, it is sometimes hard to reach millimetric nodules through a VATS incision. Therefore, some additional techniques were developed to reach such nodules little in size and which are settled on a challenging localization. In the literature, coils, hook wires, methylene blue, lipidol, and barium staining, and also ultrasound guidance were described for this aim. Herein we discuss our experience with CT-guided methylene blue labeling of small, deeply located pulmonary nodules just before VATS excision.
Method From April 2013 to October 2016, 11 patients with millimetric pulmonary nodules (average 8, 7 mm) were evaluated in our clinic. For all these patients who had strong predisposing factors for malignancy, an 18F-FDG PET-CT scan was also performed. The patients whose nodules were decided to be excised were consulted the radiology clinic. The favorable patients were taken to CT room 2 hours prior to the operation, and CT-guided methylene blue staining were performed under sterile conditions.
Results Mean nodule size of 11 patients was 8.7 mm (6, 2–12). Mean distance from the visceral pleural surface was 12.7 mm (4–29.3). Four of the nodules were located on the left (2 upper lobes, 2 lower lobes), and seven of them were on the right (four lower lobes, two upper lobes, one middle lobe). The maximum standardized uptake values (SUV max) on 18F-FDG PET/CT scan ranged between 0 and 2, 79.
Conclusion CT-guided methylene blue staining of millimetric deeply located pulmonary nodules is a safe and feasible technique that helps surgeon find these undetermined nodules by VATS technique without any need of digital palpation.
Mitochondrial protein interactome elucidated by chemical cross-linking mass spectrometry
Authors: Schweppe Devin K. , Chavez Juan D. , Lee Chi Fung , Caudal Arianne , Kruse Shane E. , Stuppard Rudy , Marcinek David J. , Shadel Gerald S. , Tian Rong , Bruce James E. 
Published: January 2017

SignificanceMitochondria meet the majority of living cells’ demand for ATP and, as important regulators of redox homeostasis, metabolite levels, and calcium buffering, are a critical link between cell energetics and signaling. Disruption of these processes can induce adaptive or pathological signaling responses to stress and under severe stress promote cell death. Mitochondria have a complex proteome with conformations and interactions that are not well understood. Mitochondrial dysfunction is a direct cause of rare inherited diseases and is implicated in common metabolic diseases and age-related pathology. This study illuminates protein interactions and conformational features of nearly one-third of the mitochondrial proteome. Network information on this scale will enable groundbreaking insights into mitochondrial function, dysfunction, and potential therapeutic targets for mitochondrial-based pathology.
Control of DEMETER DNA demethylase gene transcription in male and female gamete companion cells inArabidopsis thaliana
Authors: Park Jin-Sup , Frost Jennifer M. , Park Kyunghyuk , Ohr Hyonhwa , Park Guen Tae , Kim Seohyun , Eom Hyunjoo , Lee Ilha , Brooks Janie S. , Fischer Robert L. , Choi Yeonhee 
Published: January 2017

SignificanceTheArabidopsisDEMETER (DME) DNA demethylase is required for reproduction and endosperm gene imprinting. We investigated mechanisms that restrict DME transcription to the female and male companion cells, the central and vegetative cells, adjacent to egg and sperm cells, respectively. We delineated a region, surprisingly within theDMEgene, sufficient for proper DME expression, which rescues seed abortion and aberrant endosperm DNA methylation associated withdmemutations. We discovered overlapping DNA enhancers promoting vegetative and central cell expression, which can be used to pinpoint candidate transcription factors that regulate DME in companion cells. These results show how reproductive DNA demethylation is restricted to companion cells, thereby protecting egg and sperm cells from deleterious DNA demethylation that would be transmitted to progeny.
The JWS online simulation database
Authors: Peters Martin , Eicher Johann J , van Niekerk David D , Waltemath Dagmar , Snoep Jacky L 
Published: January 2017

Abstract

Summary
JWS Online is a web-based platform for construction, simulation and exchange of models in standard formats. We have extended the platform with a database for curated simulation experiments that can be accessed directly via a URL, allowing one-click reproduction of published results. Users can modify the simulation experiments and export them in standard formats. The Simulation database thus lowers the bar on exploring computational models, helps users create valid simulation descriptions and improves the reproducibility of published simulation experiments.

Availability and Implementation
The Simulation Database is available on line at https://jjj.bio.vu.nl/models/experiments/.
Evolutionary design of multiple genes encoding the same protein
Authors: Terai Goro , Kamegai Satoshi , Taneda Akito , Asai Kiyoshi 
Published: January 2017

Abstract

Motivation
Enhancing expression levels of a target protein is an important goal in synthetic biology. A widely used strategy is to integrate multiple copies of genes encoding a target protein into a host organism genome. Integrating highly similar sequences, however, can induce homologous recombination between them, resulting in the ultimate reduction of the number of integrated genes.

Results
We propose a method for designing multiple protein-coding sequences (i.e. CDSs) that are unlikely to induce homologous recombination, while encoding the same protein. The method, which is based on multi-objective genetic algorithm, is intended to design a set of CDSs whose nucleotide sequences are as different as possible and whose codon usage frequencies are as highly adapted as possible to the host organism. We show that our method not only successfully designs a set of intended CDSs, but also provides insight into the trade-off between nucleotide differences among gene copies and codon usage frequencies.

Availability and Implementation
Our method, named Tandem Designer, is available as a web-based application at http://tandem.trahed.jp/tandem/.

Supplementary information
Supplementary data are available at Bioinformatics online.
Unrealistic phylogenetic trees may improve phylogenetic footprinting
Authors: Nettling Martin , Treutler Hendrik , Cerquides Jesus , Grosse Ivo 
Published: January 2017

Abstract

Motivation
The computational investigation of DNA binding motifs from binding sites is one of the classic tasks in bioinformatics and a prerequisite for understanding gene regulation as a whole. Due to the development of sequencing technologies and the increasing number of available genomes, approaches based on phylogenetic footprinting become increasingly attractive. Phylogenetic footprinting requires phylogenetic trees with attached substitution probabilities for quantifying the evolution of binding sites, but these trees and substitution probabilities are typically not known and cannot be estimated easily.

Results
Here, we investigate the influence of phylogenetic trees with different substitution probabilities on the classification performance of phylogenetic footprinting using synthetic and real data. For synthetic data we find that the classification performance is highest when the substitution probability used for phylogenetic footprinting is similar to that used for data generation. For real data, however, we typically find that the classification performance of phylogenetic footprinting surprisingly increases with increasing substitution probabilities and is often highest for unrealistically high substitution probabilities close to one. This finding suggests that choosing realistic model assumptions might not always yield optimal predictions in general and that choosing unrealistically high substitution probabilities close to one might actually improve the classification performance of phylogenetic footprinting.

Availability and Implementation
The proposed PF is implemented in JAVA and can be downloaded from https://github.com/mgledi/PhyFoo

Supplementary information
Supplementary data are available at Bioinformatics online.
MetaShot: an accurate workflow for taxon classification of host-associated microbiome from shotgun metagenomic data
Authors: Fosso B , Santamaria M , D’Antonio M , Lovero D , Corrado G , Vizza E , Passaro N , Garbuglia A R , Capobianchi M R , Crescenzi M , Valiente G , Pesole G 
Published: January 2017

Abstract

Summary
Shotgun metagenomics by high-throughput sequencing may allow deep and accurate characterization of host-associated total microbiomes, including bacteria, viruses, protists and fungi. However, the analysis of such sequencing data is still extremely challenging in terms of both overall accuracy and computational efficiency, and current methodologies show substantial variability in misclassification rate and resolution at lower taxonomic ranks or are limited to specific life domains (e.g. only bacteria). We present here MetaShot, a workflow for assessing the total microbiome composition from host-associated shotgun sequence data, and show its overall optimal accuracy performance by analyzing both simulated and real datasets.

Availability and Implementation
https://github.com/bfosso/MetaShot

Supplementary information
Supplementary data are available at Bioinformatics online.
Ligandbook: an online repository for small and drug-like molecule force field parameters
Authors: Domański Jan , Beckstein Oliver , Iorga Bogdan I 
Published: January 2017

Abstract

Summary
Ligandbook is a public database and archive for force field parameters of small and drug-like molecules. It is a repository for parameter sets that are part of published work but are not easily available to the community otherwise. Parameter sets can be downloaded and immediately used in molecular dynamics simulations. The sets of parameters are versioned with full histories and carry unique identifiers to facilitate reproducible research. Text-based search on rich metadata and chemical substructure search allow precise identification of desired compounds or functional groups. Ligandbook enables the rapid set up of reproducible molecular dynamics simulations of ligands and protein-ligand complexes.

Availability and Implementation
Ligandbook is available online at https://ligandbook.org and supports all modern browsers. Parameters can be searched and downloaded without registration, including access through a programmatic RESTful API. Deposition of files requires free user registration. Ligandbook is implemented in the PHP Symfony2 framework with TCL scripts using the CACTVS toolkit.

Supplementary information
Supplementary data are available at Bioinformatics online.
H(O)TA: estimation of DNA methylation and hydroxylation levels and efficiencies from time course data
Authors: Kyriakopoulos Charalampos , Giehr Pascal , Wolf Verena 
Published: January 2017

Abstract

Motivation
Methylation and hydroxylation of cytosines to form 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) belong to the most important epigenetic modifications and their vital role in the regulation of gene expression has been widely recognized. Recent experimental techniques allow to infer methylation and hydroxylation levels at CpG dinucleotides but require a sophisticated statistical analysis to achieve accurate estimates.

Results
We present H(O)TA, a software tool based on a stochastic modeling approach, which simultaneously analyzes time course data from hairpin bisulfite sequencing and hairpin oxidative bisulfite sequencing.

Availability and Implementation
https://mosi.uni-saarland.de/HOTA
Identification of protein complexes by integrating multiple alignment of protein interaction networks
Authors: Ma Cheng-Yu , Chen Yi-Ping Phoebe , Berger Bonnie , Liao Chung-Shou 
Published: January 2017

Abstract

Motivation
Protein complexes are one of the keys to studying the behavior of a cell system. Many biological functions are carried out by protein complexes. During the past decade, the main strategy used to identify protein complexes from high-throughput network data has been to extract near-cliques or highly dense subgraphs from a single protein–protein interaction (PPI) network. Although experimental PPI data have increased significantly over recent years, most PPI networks still have many false positive interactions and false negative edge loss due to the limitations of high-throughput experiments. In particular, the false negative errors restrict the search space of such conventional protein complex identification approaches. Thus, it has become one of the most challenging tasks in systems biology to automatically identify protein complexes.

Results
In this study, we propose a new algorithm, NEOComplex (NECC- and Ortholog-based Complex identification by multiple network alignment), which integrates functional orthology information that can be obtained from different types of multiple network alignment (MNA) approaches to expand the search space of protein complex detection. As part of our approach, we also define a new edge clustering coefficient (NECC) to assign weights to interaction edges in PPI networks so that protein complexes can be identified more accurately. The NECC is based on the intuition that there is functional information captured in the common neighbors of the common neighbors as well. Our results show that our algorithm outperforms well-known protein complex identification tools in a balance between precision and recall on three eukaryotic species: human, yeast, and fly. As a result of MNAs of the species, the proposed approach can tolerate edge loss in PPI networks and even discover sparse protein complexes which have traditionally been a challenge to predict.

Availability and Implementation
http://acolab.ie.nthu.edu.tw/bionetwork/NEOComplex

Supplementary information
Supplementary data are available at Bioinformatics online.
ISPRED4: interaction sites PREDiction in protein structures with a refining grammar model
Authors: Savojardo Castrense , Fariselli Piero , Martelli Pier Luigi , Casadio Rita 
Published: January 2017

Abstract

Motivation
The identification of protein–protein interaction (PPI) sites is an important step towards the characterization of protein functional integration in the cell complexity. Experimental methods are costly and time-consuming and computational tools for predicting PPI sites can fill the gaps of PPI present knowledge.

Results
We present ISPRED4, an improved structure-based predictor of PPI sites on unbound monomer surfaces. ISPRED4 relies on machine-learning methods and it incorporates features extracted from protein sequence and structure. Cross-validation experiments are carried out on a new dataset that includes 151 high-resolution protein complexes and indicate that ISPRED4 achieves a per-residue Matthew Correlation Coefficient of 0.48 and an overall accuracy of 0.85. Benchmarking results show that ISPRED4 is one of the top-performing PPI site predictors developed so far.

Availability and Implementation
ISPRED4 and datasets used in this study are available at http://ispred4.biocomp.unibo.it.
Efficacy of the β-lactam\β-lactamase inhibitor combination is linked to WhiB4 mediated changes in redox physiology ofMycobacterium tuberculosis
Authors: Mishra Saurabh , Shukla Prashant , Bhaskar Ashima , Anand Kushi , Baloni Priyanka , Jha Rajeev Kumar , Mohan Abhilash , Rajmani Raju S. , Nagaraja V. , Chandra Nagasuma , Singh Amit 
Published: January 2017

AbstractAimsInhibition of β-lactamase by clavulanate (Clav) sensitizes multi-and extensively drug-resistantMycobacterium tuberculosis(Mtb) strains towards β-lactams such as amoxicillin (Amox). However, the underlying mechanism of howMtbresponds to Amox-Clav combination (Augmentin; AG) is not characterized.ResultsWe integrated global expression profiling with the protein-protein interaction landscape and generated a genome-scale network ofMtbin response to AG. In addition to specific targets (e.g.,peptidoglycan biosynthesis and β-lactamase), the response to AG was also centered on redox-balance, central carbon metabolism (CCM), and respiration inMtb.We discovered that AG modulates superoxide levels, NADH/NAD+balance and mycothiol redox potential (EMSH) ofMtb. Higher intra-mycobacterialEMSHpotentiates mycobactericidal efficacy of AG, whereas lowerEMSHinduces tolerance. Further,Mtbresponds to AG via a redox-sensitive transcription factor, WhiB4.MtbΔwhiB4displayed higher expression of genes involved in β-lactam resistance along with those mediating respiration, CCM and redox balance. Moreimportantly, WhiB4 binds to the promoter regions and represses transcription of genes involved in β-lactamase expression in a redox-dependent manner. Lastly, whileMtbΔwhiB4maintained internalEMSH, exhibited greater β-lactamase activity and displayed AG-tolerance, overexpression of WhiB4 induced oxidative shift inEMSHand repressed β-lactamase activity to aggravate AG-mediated killing of drug-sensitive and –resistant strains ofMtb.Innovation and ConclusionsThis work demonstrate that efficacy of β-lactam\β-lactamase inhibitor combination can be attenuated by elevating mycobacterial antioxidant capabilities and potentiated by impairing redox buffering capacity ofMtb. The functional linkage between β-lactams, redox balance, and WhiB4 can be exploited to potentiate AG action against drug-resistantMtb.
A randomized placebo-controlled trial on the antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression
Authors: Palhano-Fontes Fernanda , Barreto Dayanna , Onias Heloisa , Andrade Katia C , Novaes Morgana , Pessoa Jessica A , Mota-Rolim Sergio A , Osório Flavia , Sanches Rafael , dos Santos Rafael G , Tófoli Luís F , Oliveira Silveira Gabriela de , Yonamine Mauricio , Riba Jordi , Santos Francisco RR , Silva-Junior Antonio A , Alchieri João , Galvão-Coelho Nicole L , Lobão-Soares Bruno , Hallak Jaime , Arcoverde Emerson , Maia-de-Oliveira João P , Araújo Draulio B 
Published: January 2017

AbstractRecent open label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression. In order to further test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. Changes in depression severity were assessed with the Montgomery–Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale (HAM-D). Assessments were made at baseline, and at one (D1), two (D2) and seven (D7) days after dosing. We observed significant antidepressant effects of ayahuasca when compared to placebo at all timepoints. MADRS scores were significantly lower in the ayahuasca group compared to placebo (at D1 and D2: p=0.04; and at D7: p<0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen’ s d=0.84; D2: Cohen’ s d=0.84; D7: Cohen’ s d=1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% vs. 27%; p=0.04), while remission rate was marginally significant at D7 (36% vs. 7%, p=0.054). To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression.
Fine-scale landscape genomics helps explain the slow spread ofWolbachiathrough theAedes aegyptipopulation in Cairns, Australia
Authors: Schmidt Thomas. L. , Filipović Igor. , Hoffmann Ary A. , Rašić Gordana 
Published: January 2017

AbstractThe endosymbiotic bacteriumWolbachiasuppresses the capacity for arboviral transmission in the mosquitoAedes aegypti, and can spread through wild mosquito populations following local introductions. Recent introductions in Cairns, Australia have demonstrated slower than expected spread, that could be due to: i) barriers toAe. aegyptidispersal; ii) leptokurtically distributed dispersal distances; and iii) intergenerational loss ofWolbachia. We investigated these three potential causes using genome-wide single-nucleotide polymorphisms (SNPs) and an assay for theWolbachiainfectionwMel in 161Ae. aegypticollected from Cairns in 2015. We observed a significant barrier effect of Cairns highways onAe. aegyptidispersal using distance-based redundancy analysis and patch-based simulation analysis. We detected putative full-siblings in ovitraps 1312m apart, suggesting long-distance female movement likely mediated by human transport. Finally, we found a pair of full-siblings of different infection status, suggesting loss ofWolbachiain the field. While the long-distance movement andWolbachialoss currently represent single observations, these findings together with the identified dispersal barriers can contribute to the slow spread ofWolbachiathrough theAe. aegyptipopulation in Cairns. Our landscape genomics approach can be extended to other host/symbiont systems that are being considered for biocontrol.
Experimental support that natural selection has shaped the latitudinal distribution of mitochondrial haplotypes in AustralianDrosophila melanogaster
Authors: Camus M. Florencia , Wolff Jonci N. , Sgrò Carla M. , Dowling Damian K. 
Published: January 2017

AbstractCellular metabolism is regulated by enzyme complexes within the mitochondrion, the function of which are sensitive to the prevailing temperature. Such thermal sensitivity, coupled with the observation that population frequencies of mitochondrial haplotypes tend to associate with latitude, altitude or climatic regions across species distributions, led to the hypothesis that thermal selection has played a role in shaping standing variation in the mitochondrial DNA (mtDNA) sequence. This hypothesis, however, remains controversial, and requires evidence that the distribution of haplotypes observed in nature corresponds with the capacity of these haplotypes to confer differences in thermal tolerance. Specifically, haplotypes predominating in tropical climates are predicted to encode increased tolerance to heat stress, but decreased tolerance to cold stress. We present direct evidence for these predictions, using mtDNA haplotypes sampled from the Australian distribution ofDrosophila melanogaster. We show that the ability of flies to tolerate extreme thermal challenges is affected by sequence variation across mtDNA haplotypes, and that the thermal performance associated with each haplotype corresponds with its latitudinal prevalence. The haplotype that predominates at low (subtropical) latitudes confers greater resilience to heat stress, but lower resilience to cold stress, than haplotypes predominating at higher (temperate) latitudes. We explore molecular mechanisms that might underlie these responses, presenting evidence that the effects are in part regulated by SNPs that do not change the protein sequence. Our findings suggest that standing variation in the mitochondrial genome can be shaped by thermal selection, and could therefore contribute to evolutionary adaptation under climatic stress.