XY-Meta: A High-Efficiency Search Engine for Large-Scale Metabolome Annotation with Accurate FDR Estimation.

FDR control has been a huge challenge for large-scale metabolome annotation. Although recent research indicated that the target-decoy strategy could be implemented to estimate FDR, it is hard to perform FDR control due to the difficulty of getting a reliable decoy database because of the complex fragmentation mechanism of metabolites and ubiquitous isomers. To tackle this problem, we developed a decoy generation method, which generates forged spectra from the reference target database by preserving the original reference signals to simulate the presence of isomers of metabolites. Benchmarks on GNPS data sets in Passatutto showed that the decoy database generated by our method is closer to the actual FDR than other methods, especially in the low FDR range (0-0.05). Large-scale metabolite annotation on 35 data sets showed that strict FDR reduced the number of annotated metabolites but increased the spectral efficiency, indicating the necessity of quality control. We recommended that the FDR threshold should be set to 0.01 in large-scale metabolite annotation. We implemented decoy generation, database search, and FDR control into a search engine called XY-Meta. It facilitates large-scale metabolome annotation applications.

The oyster genome reveals stress adaptation and complexity of shell formation.

The Pacific oyster Crassostrea gigas belongs to one of the most species-rich but genomically poorly explored phyla, the Mollusca. Here we report the sequencing and assembly of the oyster genome using short reads and a fosmid-pooling strategy, along with transcriptomes of development and stress response and the proteome of the shell. The oyster genome is highly polymorphic and rich in repetitive sequences, with some transposable elements still actively shaping variation. Transcriptome studies reveal an extensive set of genes responding to environmental stress. The expansion of genes coding for heat shock protein 70 and inhibitors of apoptosis is probably central to the oyster's adaptation to sessile life in the highly stressful intertidal zone. Our analyses also show that shell formation in molluscs is more complex than currently understood and involves extensive participation of cells and their exosomes. The oyster genome sequence fills a void in our understanding of the Lophotrochozoa.

BASE: a practical de novo assembler for large genomes using long NGS reads.

BACKGROUND: De novo genome assembly using NGS data remains a computation-intensive task especially for large genomes. In practice, efficiency is often a primary concern and favors using a more efficient assembler like SOAPdenovo2. Yet SOAPdenovo2, based on de Bruijn graph, fails to take full advantage of longer NGS reads (say, 150 bp to 250 bp from Illumina HiSeq and MiSeq). Assemblers that are based on string graphs (e.g., SGA), though less popular and also very slow, are more favorable for longer reads. METHODS: This paper shows a new de novo assembler called BASE. It enhances the classic seed-extension approach by indexing the reads efficiently to generate adaptive seeds that have high probability to appear uniquely in the genome. Such seeds form the basis for BASE to build extension trees and then to use reverse validation to remove the branches based on read coverage and paired-end information, resulting in high-quality consensus sequences of reads sharing the seeds. Such consensus sequences are then extended to contigs. RESULTS: Experiments on two bacteria and four human datasets shows the advantage of BASE in both contig quality and speed in dealing with longer reads. In the experiment on bacteria, two datasets with read length of 100 bp and 250 bp were used.. Especially for the 250 bp dataset, BASE gives much better quality than SOAPdenovo2 and SGA and is simlilar to SPAdes. Regarding speed, BASE is consistently a few times faster than SPAdes and SGA, but still slower than SOAPdenovo2. BASE and Soapdenov2 are further compared using human datasets with read length 100 bp, 150 bp and 250 bp. BASE shows a higher N50 for all datasets, while the improvement becomes more significant when read length reaches 250 bp. Besides, BASE is more-meory efficent than SOAPdenovo2 when sequencing data with error rate. CONCLUSIONS: BASE is a practically efficient tool for constructing contig, with significant improvement in quality for long NGS reads. It is relatively easy to extend BASE to include scaffolding.

Insights into salt tolerance from the genome of Thellungiella salsuginea.

Thellungiella salsuginea, a close relative of Arabidopsis, represents an extremophile model for abiotic stress tolerance studies. We present the draft sequence of the T. salsuginea genome, assembled based on ~134-fold coverage to seven chromosomes with a coding capacity of at least 28,457 genes. This genome provides resources and evidence about the nature of defense mechanisms constituting the genetic basis underlying plant abiotic stress tolerance. Comparative genomics and experimental analyses identified genes related to cation transport, abscisic acid signaling, and wax production prominent in T. salsuginea as possible contributors to its success in stressful environments.

Aluminum corrosion-passivation regulation prolongs aqueous batteries life.

Aluminum current collectors are widely used in nonaqueous batteries owing to their cost-effectiveness, lightweightness, and ease of fabrication. However, they are excluded from aqueous batteries due to their severe corrosion in aqueous solutions. Here, we propose hydrolyzation-type anodic additives to form a robust passivation layer to suppress corrosion. These additives dramatically lower the corrosion current density of aluminum by nearly three orders of magnitude to ~10-6 A cm-2. In addition, realizing that electrochemical corrosion accompanies anode prelithiation, we propose a prototype of self-prolonging aqueous Li-ion batteries (Al ||LiMn2O4 ||TiO2), whose capacity retention rises from 49.5% to 70.1% after 200 cycles. A sacrificial aluminum electrode where electrochemical corrosion is utilized is introduced as an electron supplement to prolong the cycling life of aqueous batteries. Our work addresses the short-life issue of aqueous batteries resulting from the corrosion of the current collector and lithium loss from side reactions.

COPE: an accurate k-mer-based pair-end reads connection tool to facilitate genome assembly.

MOTIVATION: The boost of next-generation sequencing technologies provides us with an unprecedented opportunity for elucidating genetic mysteries, yet the short-read length hinders us from better assembling the genome from scratch. New protocols now exist that can generate overlapping pair-end reads. By joining the 3' ends of each read pair, one is able to construct longer reads for assembling. However, effectively joining two overlapped pair-end reads remains a challenging task. RESULT: In this article, we present an efficient tool called Connecting Overlapped Pair-End (COPE) reads, to connect overlapping pair-end reads using k-mer frequencies. We evaluated our tool on 30× simulated pair-end reads from Arabidopsis thaliana with 1% base error. COPE connected over 99% of reads with 98.8% accuracy, which is, respectively, 10 and 2% higher than the recently published tool FLASH. When COPE is applied to real reads for genome assembly, the resulting contigs are found to have fewer errors and give a 14-fold improvement in the N50 measurement when compared with the contigs produced using unconnected reads. AVAILABILITY AND IMPLEMENTATION: COPE is implemented in C++ and is freely available as open-source code at ftp://ftp.genomics.org.cn/pub/cope. CONTACT: twlam@cs.hku.hk or luoruibang@genomics.org.cn

pIRS: Profile-based Illumina pair-end reads simulator.

MOTIVATION: The next-generation high-throughput sequencing technologies, especially from Illumina, have been widely used in re-sequencing and de novo assembly studies. However, there is no existing software that can simulate Illumina reads with real error and quality distributions and coverage bias yet, which is very useful in relevant software development and study designing of sequencing projects. RESULTS: We provide a software package, pIRS (profile-based Illumina pair-end reads simulator), which simulates Illumina reads with empirical Base-Calling and GC%-depth profiles trained from real re-sequencing data. The error and quality distributions as well as coverage bias patterns of simulated reads using pIRS fit the properties of real sequencing data better than existing simulators. In addition, pIRS also comes with a tool to simulate the heterozygous diploid genomes. AVAILABILITY: pIRS is written in C++ and Perl, and is freely available at ftp://ftp.genomics.org.cn/pub/pIRS/.

Recycling and Recovery of Deactivated CsPbBr3 Perovskite after Photocatalytic CO2 Reduction Reaction.

CsPbBr3 perovskite nanocrystals have emerged as promising candidates for photocatalysis. However, their conversion efficiency is hampered by material instability, and the accumulation of deactivated perovskites produced after photocatalytic reactions raises significant environmental concerns. To address this issue, we developed a mechanochemical grinding approach assisted by oleylamine as an additive to restore the optical properties and photocatalytic activity of deactivated CsPbBr3, which was due to aggregation in the photocatalytic CO2 reduction reaction. Upon regeneration, the CsPbBr3 nanocrystals exhibited an average length of 34.21 nm and an average width of 20.86 nm, demonstrating optical properties comparable to those of the pristine CsPbBr3 nanocrystals. Moreover, they achieved a conversion efficiency of 88.7% compared with pristine CsPbBr3 nanocrystals in the photocatalytic CO2 reduction reaction. This method effectively enhanced the utilization of CsPbBr3, offering a novel approach for the recycling and recovery of perovskite materials and thereby minimizing material waste and environmental pollution.

An investigation of long-term outcome of rabbit anti-thymocyte globulin and cyclosporine therapy for pediatric severe aplastic anemia.

Children with severe aplastic anemia (SAA) face heterogeneous prognoses after immunosuppressive therapy (IST). There are few models that can predict the long-term outcomes of IST for these patients. The objective of this paper is to develop a more effective prediction model for SAA prognosis based on clinical electronic medical records from 203 children with newly diagnosed SAA. In the early stage, a novel model for long-term outcomes of SAA patients with IST was developed using machine-learning techniques. Among the indicators related to long-term efficacy, white blood cell count, lymphocyte count, absolute reticulocyte count, lymphocyte ratio in bone-marrow smears, C-reactive protein, and the level of IL-6, IL-8 and vitamin B12 in the early stage are strongly correlated with long-term efficacy (P < .05). Taken together, we analyzed the long-term outcomes of rabbit anti-thymocyte globulin and cyclosporine therapy for children with SAA through machine-learning techniques, which may shorten the observation period of therapeutic effects and reduce treatment costs and time.

An Electric-Field-Reinforced Hydrophobic Cationic Sieve Lowers the Concentration Threshold of Water-In-Salt Electrolytes.

High-concentration water-in-salt (WIS) electrolytes expand the stable electrochemical window of aqueous electrolytes, leading to the advent of high-voltage (above 2 V) aqueous Li-ion batteries (ALIBs). However, the high lithium salt concentration electrolytes of ALIBs result in their high cost and deteriorate kinetic performance. Therefore, it is challenging for ALIBs to explore aqueous electrolytes with appropriate concentration to balance the electrochemical window and kinetic performance as well as the cost. In contrast to maintaining high concentrations of aqueous electrolytes (>20 m), a small number of hydrophobic cations are introduced to a much lower electrolyte concentration (13.8 m), and it is found that, compared with WIS electrolytes, ALIBs with these concentration-lowered electrolytes possess a compatible stable electrochemical window (3.23 V) and achieve better kinetic performance. These findings originate from the added cations, which form an electric-field-reinforced hydrophobic cationic sieve (HCS) that blocks water away from the anode and suppresses the hydrogen evolution reaction. Meanwhile, the lower electrolyte concentration provides significant benefits to ALIBs, including lower cost, better rate capability (lower viscosity of 18 cP and higher ionic conductivity of 22 mS cm-1 at 25 °C), and improved low-temperature performance (liquidus temperature of -10.18 °C).

Acetylcholine inhibits hypoxia-induced tumor necrosis factor-α production via regulation of MAPKs phosphorylation in cardiomyocytes.

Recent findings have reported that up-regulation of tumor necrosis factor-alpha (TNF-α) induced by myocardial hypoxia aggravates cardiomyocyte injury. Acetylcholine (ACh), the principle vagal neurotransmitter, protects cardiomyocytes against hypoxia by inhibiting apoptosis. However, it is still unclear whether ACh regulates TNF-α production in cardiomyocytes after hypoxia. The concentration of extracellular TNF-α was increased in a time-dependent manner during hypoxia. Furthermore, ACh treatment also inhibited hypoxia-induced TNF-α mRNA and protein expression, caspase-3 activation, cell death and the production of reactive oxygen species (ROS) in cardiomyocytes. ACh treatment prevented the hypoxia-induced increase in p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) phosphorylation, and increased extracellular signal-regulated kinase (ERK) phosphorylation. Co-treatment with atropine, a non-selective muscarinic acetylcholine receptor antagonist, or methoctramine, a selective type-2 muscarinic acetylcholine (M(2) ) receptor antagonist, abrogated the effects of ACh treatment in hypoxic cardiomyocytes. Co-treatment with hexamethonium, a non-selective nicotinic receptor antagonist, and methyllycaconitine, a selective alpha7-nicotinic acetylcholine receptor antagonist, had no effect on ACh-treated hypoxic cardiomyocytes. In conclusion, these results demonstrate that ACh activates the M(2) receptor, leading to regulation of MAPKs phosphorylation and, subsequently, down-regulation of TNF-α production. We have identified a novel pathway by which ACh mediates cardioprotection against hypoxic injury in cardiomyocytes.

Alterations of muscarinic acetylcholine receptors-2, 4 and α7-nicotinic acetylcholine receptor expression after ischaemia / reperfusion in the rat isolated heart.

1. Cardiac acetylcholine receptors are involved in the negative inotropic effect of the vagus and the protection of the stimulated vagal nerve against myocardial ischaemic injury. Acetylcholine receptors consist of five types of muscarinic acetylcholine receptors (M AChR) and several nicotinic acetylcholine receptors (nAChR). Notably, ischaemic heart disease is accompanied by substantial withdrawal of vagal activity. However, it is not entirely clear what the changes of M(2,4) AChR and α7-nAChR expression are after cardiac ischaemia/reperfusion (I/R) injury. 2. Cardiac functions were continuously recorded in Langendorff mode during 30 min of ischaemia and 60 min of reperfusion. Lactate dehydrogenase (LDH) leakage was measured. M(2,4) AChRs and α7-nAChR expression were measured by reverse transcription polymerase chain reaction and western blot. 3. In hearts exposed to I/R injury, left ventricular development pressure, heart rate and ± dP/dt decreased significantly compared with the controls. LDH leakage increased with respect to the controls during reperfusion. 4. In normal hearts, expression of M(2,4) AChR in the left ventricle were lower than in atria and the right ventricle, whereas expression of α7-nAChR was dramatically higher in the left ventricle and right ventricle than the atria. After reperfusion, the mRNA and protein expression of M(2) AChR increased notably in the left and right ventricle, and α7-nAChR was enhanced significantly in the left ventricle. M(4) AChR mRNA expression reduced notably after ischaemia and recovered to the control level after reperfusion in the atria, but the protein level did not change. 5. In conclusion, the increase in M(2) AChR and α7-nAChR after reperfusion might be the compensatory response to myocardial I/R injury, providing new information for treatment of myocardial I/R injury.

Involvement of volume-sensitive Cl- channels in the proliferation of human subcutaneous pre-adipocytes.

1. Obesity is a significant challenge in terms of public health and preventive medicine. Inhibition of pre-adipocyte proliferation is believed to be important in the proposed anti-obesity mechanism. The aim of the present study was to examine the interplay between Cl(-) channels and their possible involvement in the proliferation of undifferentiated human pre-adipocytes. 2. Pre-adipocytes were isolated from human abdominal subcutaneous adipose tissue. Membrane ion currents were recorded using the whole-cell patch-clamp technique. Expression of the Cl(-) channel ClC-3 gene and protein was determined by reverse transcription-polymerase chain reaction (RT-PCR) and western blot, respectively. Cell proliferation was evaluated using the [(3)H]-thymidine incorporation assay. 3. Electrophysiological recordings revealed a volume-sensitive Cl(-) current (I(Cl.vol)) expressed in pre-adipocytes that was activated under hyposmotic conditions (external osmolarity decreased by 80%) and inhibited by the Cl(-) channel blocker tamoxifen. 4. Expression of the ClC-3 channel gene and protein was confirmed by RT-PCR and western blot analysis. Blocking I(Cl.vol) with tamoxifen supressed the proliferation of pre-adipocytes in a concentration-dependent manner. 5. Collectively, the results of the present study indicate that the volume-sensitive Cl(-) channel participates in regulation of the proliferation of human subcutaneous pre-adipocytes.

Exercise benefits cardiovascular health in hyperlipidemia rats correlating with changes of the cardiac vagus nerve.

The role of exercise training on hemodynamic parameters, blood lipid profiles, inflammatory cytokines, cholinesterase-positive nerves and muscarinic cholinergic (M(2)) receptors expression in the heart was investigated in Sprague-Dawley male rats with hyperlipidemia (HL). The rats were subjected to a high-fat diet and exercise training for 8 weeks, and then the hemodynamic parameters, the profiles of blood lipid and inflammatory cytokines, and the expression of cholinesterase-positive nerves and M(2) receptors were measured. HL rats displayed cardiac dysfunction, dysregulation of inflammatory cytokines, and decreased cholinesterase-positive nerves and M(2) receptors expression. The combination of hyperlipidemia with exercise training (AT) restored the profiles of blood lipids and the levels of inflammatory cytokines. In addition, AT and HL + AT improved cardiac function with increasing cholinesterase-positive nerves and M(2) receptors expression. Overall, these data show that the increased expression of cholinesterase-positive nerves and M(2) receptors in the heart is partially responsible for the benefits of exercise training on cardiac function in hyperlipidemia rats.

Water-in-Salt Electrolyte Promotes High-Capacity FeFe(CN)6 Cathode for Aqueous Al-Ion Battery.

Prussian blue analogues (PBAs) are considered to be ideal multivalent cation host materials due to their unique open-framework structure. In aqueous solution, however, the PBAs' cathodes have a low reversible capacity limited by the single electrochemical group Fe(CN)63- and high crystal water content. They also suffer from fast cycle fading, resulting from significant oxygen/hydrogen evolution and cathode dissolution. In this work, a high-capacity PBA-type FeFe(CN)6 cathode with double transition metal redox sites is successfully demonstrated in 5 m Al(CF3SO3)3 Water-in-Salt electrolyte (Al-WISE). Due to Al-WISE having a wide electrochemical window (2.65 V) and low dissolution of the cathode, our PBA cathode exhibits a high discharge capacity of 116 mAh/g and the superior cycle stability >100 cycles with capacity fading of 0.39% per cycle.

[Vagal control of cardiac functions and vagal protection of ischemic myocardium].

The physiological activities of the cardiovascular system are under the control of autonomic nervous system (ANS). Recent researches have found that autonomic dysfunction, especially the withdrawal of vagal activity, was closely related to the etiology, course and prognosis of cardiovascular disease (CVD). Based on the current status and our achievements in this area, we discuss vagal regulation of different parts of the heart and the mechanism of vagal protection of myocardium. Using a force transducer and standard microelectrodes recording technology, we found that the vagus nerve transmitter--acetylcholine (ACh) had direct effects on ventricular myocytes in mammals: It inhibited the contractility and shortened the action potential duration of cardiac myocytes. We proved the existence of muscarinic receptors and vagal nerves innervation in ventricle with histochemical staining and molecular biological methods. Furthermore, ACh-activated potassium channel (KACh) was found in the ventricles of some animals by patch-clamp. Fade of the current (IK.ACh) to ACh in atrium was found in previous research, which was related to the muscarinic receptors and phosphorylation of G protein or potassium channel. However, the mechanism of the fade in ventricle needs to be further investigated. Combined with autonomic nervous evaluation methods (heart rate variability analysis) and relevant animal models, we studied the regulation of ANS during normal and morbid state, and proved the age-associated changes and compensatory effects of vagal control of hemodynamics after unilateral vagotomy. By increasing the vagal tension (ACh induced-preconditioning/postconditioning, aerobic exercise, beta receptor antagonist), we demonstrated protective effects of the vagus nerve on the ischemic myocardium and mechanism of the cholinergic anti-inflammatory effects on the inflammatory reaction induced by reperfusion injury. Evaluating cardiac autonomic nervous regulation and improving balance between sympathetic and vagal nerve will provide an important basis for the prevention and treatment of CVD.

Erratum: SOAPdenovo2: an empirically improved memory-efficient short-read de novo assembler.

[This corrects the article DOI: 10.1186/2047-217X-1-18.].

De novo assembly of a haplotype-resolved human genome.

The human genome is diploid, and knowledge of the variants on each chromosome is important for the interpretation of genomic information. Here we report the assembly of a haplotype-resolved diploid genome without using a reference genome. Our pipeline relies on fosmid pooling together with whole-genome shotgun strategies, based solely on next-generation sequencing and hierarchical assembly methods. We applied our sequencing method to the genome of an Asian individual and generated a 5.15-Gb assembled genome with a haplotype N50 of 484 kb. Our analysis identified previously undetected indels and 7.49 Mb of novel coding sequences that could not be aligned to the human reference genome, which include at least six predicted genes. This haplotype-resolved genome represents the most complete de novo human genome assembly to date. Application of our approach to identify individual haplotype differences should aid in translating genotypes to phenotypes for the development of personalized medicine.

Two Antarctic penguin genomes reveal insights into their evolutionary history and molecular changes related to the Antarctic environment.

BACKGROUND: Penguins are flightless aquatic birds widely distributed in the Southern Hemisphere. The distinctive morphological and physiological features of penguins allow them to live an aquatic life, and some of them have successfully adapted to the hostile environments in Antarctica. To study the phylogenetic and population history of penguins and the molecular basis of their adaptations to Antarctica, we sequenced the genomes of the two Antarctic dwelling penguin species, the Adélie penguin [Pygoscelis adeliae] and emperor penguin [Aptenodytes forsteri]. RESULTS: Phylogenetic dating suggests that early penguins arose ~60 million years ago, coinciding with a period of global warming. Analysis of effective population sizes reveals that the two penguin species experienced population expansions from ~1 million years ago to ~100 thousand years ago, but responded differently to the climatic cooling of the last glacial period. Comparative genomic analyses with other available avian genomes identified molecular changes in genes related to epidermal structure, phototransduction, lipid metabolism, and forelimb morphology. CONCLUSIONS: Our sequencing and initial analyses of the first two penguin genomes provide insights into the timing of penguin origin, fluctuations in effective population sizes of the two penguin species over the past 10 million years, and the potential associations between these biological patterns and global climate change. The molecular changes compared with other avian genomes reflect both shared and diverse adaptations of the two penguin species to the Antarctic environment.

Whole-genome sequencing of Oryza brachyantha reveals mechanisms underlying Oryza genome evolution.

The wild species of the genus Oryza contain a largely untapped reservoir of agronomically important genes for rice improvement. Here we report the 261-Mb de novo assembled genome sequence of Oryza brachyantha. Low activity of long-terminal repeat retrotransposons and massive internal deletions of ancient long-terminal repeat elements lead to the compact genome of Oryza brachyantha. We model 32,038 protein-coding genes in the Oryza brachyantha genome, of which only 70% are located in collinear positions in comparison with the rice genome. Analysing breakpoints of non-collinear genes suggests that double-strand break repair through non-homologous end joining has an important role in gene movement and erosion of collinearity in the Oryza genomes. Transition of euchromatin to heterochromatin in the rice genome is accompanied by segmental and tandem duplications, further expanded by transposable element insertions. The high-quality reference genome sequence of Oryza brachyantha provides an important resource for functional and evolutionary studies in the genus Oryza.