The highly anticipated transition from next generation sequencing (NGS) to third generation sequencing (3GS) has been difficult primarily due to high error rates and excessive sequencing cost. The ...high error rates make the assembly of long erroneous reads of large genomes challenging because existing software solutions are often overwhelmed by error correction tasks. Here we report a hybrid assembly approach that simultaneously utilizes NGS and 3GS data to address both issues. We gain advantages from three general and basic design principles: (i) Compact representation of the long reads leads to efficient alignments. (ii) Base-level errors can be skipped; structural errors need to be detected and corrected. (iii) Structurally correct 3GS reads are assembled and polished. In our implementation, preassembled NGS contigs are used to derive the compact representation of the long reads, motivating an algorithmic conversion from a de Bruijn graph to an overlap graph, the two major assembly paradigms. Moreover, since NGS and 3GS data can compensate for each other, our hybrid assembly approach reduces both of their sequencing requirements. Experiments show that our software is able to assemble mammalian-sized genomes orders of magnitude more quickly than existing methods without consuming a lot of memory, while saving about half of the sequencing cost.
Long-read sequence assembly of the gorilla genome Gordon, David; Huddleston, John; Chaisson, Mark J. P. ...
Science (American Association for the Advancement of Science),
04/2016, Letnik:
352, Številka:
6281
Journal Article
Recenzirano
Odprti dostop
Accurate sequence and assembly of genomes is a critical first step for studies of genetic variation. We generated a high-quality assembly of the gorilla genome using single-molecule, real-time ...sequence technology and a string graph de novo assembly algorithm. The new assembly improves contiguity by two to three orders of magnitude with respect to previously released assemblies, recovering 87% of missing reference exons and incomplete gene models. Although regions of large, high-identity segmental duplications remain largely unresolved, this comprehensive assembly provides new biological insight into genetic diversity, structural variation, gene loss, and representation of repeat structures within the gorilla genome. The approach provides a path forward for the routine assembly of mammalian genomes at a level approaching that of the current quality of the human genome.
•Indigenous and local knowledge systems carry insights for stewardship in the Anthropocene.•Bridging knowledge systems requires attention to actors, institutions, and processes.•Key tasks for ...successful bridging are to mobilise, translate, negotiate, synthesise and apply.•Mobilisation is often overlooked but can strengthen environmental governance by communities.•Engagement of knowledge holders in all five tasks creates useful knowledge for sustainability.
Indigenous peoples and local communities live in, manage and own vast areas often rich in biodiversity and critical for ecosystem services. Bridging indigenous and local knowledge systems with scientific knowledge systems is vital to enhance knowledge, practice, and ethics to move towards sustainability at multiple scales. We focus on international science-policy processes and present a framework for evidence-based guidance on how tasks to mobilise, translate, negotiate, synthesise and apply multiple forms of evidence can bridge knowledge systems. Effective engagement of actors, institutions and knowledge-sharing processes is crucial in each of these tasks. We use examples from the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) and the Convention on Biological Diversity (CBD) to illustrate and discuss our framework.
The gain-of-function MUC5B promoter variant rs35705950 is the dominant risk factor for developing idiopathic pulmonary fibrosis (IPF). Here we show in humans that MUC5B, a mucin thought to be ...restricted to conducting airways, is co-expressed with surfactant protein C (SFTPC) in type 2 alveolar epithelia and in epithelial cells lining honeycomb cysts, indicating that cell types involved in lung fibrosis in distal airspace express MUC5B. In mice, we demonstrate that Muc5b concentration in bronchoalveolar epithelia is related to impaired mucociliary clearance (MCC) and to the extent and persistence of bleomycin-induced lung fibrosis. We also establish the ability of the mucolytic agent P-2119 to restore MCC and to suppress bleomycin-induced lung fibrosis in the setting of Muc5b overexpression. Our findings suggest that mucociliary dysfunction might play a causative role in bleomycin-induced pulmonary fibrosis in mice overexpressing Muc5b, and that MUC5B in distal airspaces is a potential therapeutic target in humans with IPF.
Abstract
Metagenomic samples are snapshots of complex ecosystems at work. They comprise hundreds of known and unknown species, contain multiple strain variants and vary greatly within and across ...environments. Many microbes found in microbial communities are not easily grown in culture making their DNA sequence our only clue into their evolutionary history and biological function. Metagenomic assembly is a computational process aimed at reconstructing genes and genomes from metagenomic mixtures. Current methods have made significant strides in reconstructing DNA segments comprising operons, tandem gene arrays and syntenic blocks. Shorter, higher-throughput sequencing technologies have become the de facto standard in the field. Sequencers are now able to generate billions of short reads in only a few days. Multiple metagenomic assembly strategies, pipelines and assemblers have appeared in recent years. Owing to the inherent complexity of metagenome assembly, regardless of the assembly algorithm and sequencing method, metagenome assemblies contain errors. Recent developments in assembly validation tools have played a pivotal role in improving metagenomics assemblers. Here, we survey recent progress in the field of metagenomic assembly, provide an overview of key approaches for genomic and metagenomic assembly validation and demonstrate the insights that can be derived from assemblies through the use of assembly validation strategies. We also discuss the potential for impact of long-read technologies in metagenomics. We conclude with a discussion of future challenges and opportunities in the field of metagenomic assembly and validation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In a randomized trial, patients with coronary artery disease and an ejection fraction of 35% or less were randomly assigned to undergo either coronary-artery bypass grafting (CABG) or CABG plus ...surgical ventricular reconstruction. At a median of 48 months, there was no significant difference between the two groups in the primary outcome of death or hospitalization for cardiac causes.
Patients with coronary artery disease and an ejection fraction of 35% or less were randomly assigned to undergo either coronary-artery bypass grafting (CABG) or CABG plus surgical ventricular reconstruction. At a median of 48 months, there was no significant difference in the primary outcome of death or hospitalization for cardiac causes.
Coronary artery disease is the predominant cause of heart failure, which is a major cause of death and disability throughout the world. Evidence-based medical therapy has been shown to reduce symptoms and increase survival in patients with heart failure and coronary artery disease.
1
In addition, selected patients may benefit from surgical revascularization by means of coronary-artery bypass grafting (CABG), especially if the coronary anatomy is suitable for such surgery and if there is evidence of myocardial viability.
2
,
3
The reduction in left ventricular function that can occur after myocardial infarction is typically accompanied by left ventricular remodeling, a process that . . .
Oligodendrocytes in the mammalian brain are continuously generated from NG2 cells throughout postnatal life. However, it is unclear when the decision is made for NG2 cells to self-renew or ...differentiate into oligodendrocytes after cell division. Using a combination of in vivo and ex vivo imaging and fate analysis of proliferated NG2 cells in fixed tissue, we demonstrate that in the postnatal developing mouse brain, the majority of divided NG2 cells differentiate into oligodendrocytes during a critical age-specific temporal window of 3-8 d. Notably, within this time period, damage to myelin and oligodendrocytes accelerated oligodendrocyte differentiation from divided cells, and whisker removal decreased the survival of divided cells in the deprived somatosensory cortex. These findings indicate that during the critical temporal window of plasticity, the fate of divided NG2 cells is sensitive to modulation by external signals.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
To describe the test construction procedure and evaluate the internal consistency, criterion-referenced validity, and diagnostic accuracy of the Child/Adolescent Self-Report Version of the UCLA PTSD ...Reaction Index for DSM-5 (RI-5) across 2 independent samples.
Study 1 examined the clarity, developmental appropriateness, acceptability of individual RI-5 items, and internal consistency and criterion-referenced validity of the full test. The study 1 sample included 486 youth recruited from 2 major US cities who completed the RI-5 and a measure of depression. Study 2 evaluated the reliability and diagnostic accuracy of the RI-5 in 41 treatment-seeking youth who completed the RI-5 and a "gold standard" structured diagnostic interview, the Clinician-Administered PTSD Scale for DSM-5-Child/Adolescent Version.
RI-5 total scale scores showed excellent internal consistency in the 2 samples. Study 1 provided evidence of criterion-referenced validity, in that total scale scores correlated positively with depressive symptoms. Study 2 provided evidence of diagnostic accuracy (including discriminant-groups validity). RI-5 total scores discriminated youth with from youth without PTSD as benchmarked against the structured diagnostic interview. Further, receiver operating characteristic analyses using a total score of 35 provided excellent diagnostic classification accuracy (area under the curve 0.94).
The developmental appropriateness and diagnostic accuracy of the RI-5 support its utility for clinical assessment, case conceptualization, and treatment planning in different child-serving systems, including schools, juvenile justice, child welfare, and mental health.
Polymers with high permeability and strong size-sieving ability are needed for H2/CO2 separation at temperatures ranging from 100 to 300 °C to enable an energy-efficient precombustion CO2 capture ...process. However, such polymers usually suffer from a permeability/selectivity tradeoff, that is, polymers with high permeability tend to exhibit a weak size-sieving ability and thus low selectivity. Herein, we demonstrate that carbonization of a suitable polymer precursor (i.e., polybenzimidazole or PBI) generates microcavities (leading to high H2 permeability) and ultramicroporous channels (leading to strong size-sieving ability and thus high H2/CO2 selectivity). Specifically, carbonization of PBI at 900 °C (CMS@900) doubles H2 permeability and increases H2/CO2 selectivity from 14 to 80 at 150 °C. When tested with simulated syngas-containing equimolar H2 and CO2 in the presence of water vapor for 120 h, CMS@900 exhibits stable H2 permeability of ≈36 barrer and H2/CO2 selectivity of ≈53 at 150 °C, above Robeson’s 2008 upper bound and demonstrating robustness against physical aging and CO2 plasticization.
Locomotor adaptation is a motor learning process used to alter spatiotemporal elements of walking that are driven by prediction errors, a discrepancy between the expected and actual outcomes of our ...actions. Sensory and reward prediction errors are two different types of prediction errors that can facilitate locomotor adaptation. Reward and punishment feedback generate reward prediction errors but have demonstrated mixed effects on upper extremity motor learning, with punishment enhancing adaptation, and reward supporting motor memory. However, an in-depth behavioral analysis of these distinct forms of feedback is sparse in locomotor tasks.
For this study, three groups of healthy young adults were divided into distinct feedback groups Supervised, Reward, Punishment and performed a novel locomotor adaptation task where each participant adapted their knee flexion to 30 degrees greater than baseline, guided by visual supervised or reinforcement feedback (Adaptation). Participants were then asked to recall the new walking pattern without feedback (Retention) and after a washout period with feedback restored (Savings).
We found that all groups learned the adaptation task with external feedback. However, contrary to our initial hypothesis, enhancing sensory feedback with a visual representation of the knee angle (Supervised) accelerated the rate of learning and short-term retention in comparison to monetary reinforcement feedback. Reward and Punishment displayed similar rates of adaptation, short-term retention, and savings, suggesting both types of reinforcement feedback work similarly in locomotor adaptation. Moreover, all feedback enhanced the aftereffect of locomotor task indicating changes to implicit learning.
These results demonstrate the multi-faceted nature of reinforcement feedback on locomotor adaptation and demonstrate the possible different neural substrates that underly reward and sensory prediction errors during different motor tasks.
PDF
