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Themed collection 2015 Hot Articles in Molecular BioSystems

59 items
Review Article

Reconstructing and analysing cellular states, space and time from gene expression profiles of many cells and single cells

Gene expression profiling is a fast, cheap and standardised analysis that provides a high dimensional measurement of the state of a biological sample, including of single cells. Computational methods to reconstruct the composition of samples and spatial and temporal information from expression profiles are described, as well as how they can be used to describe the effects of genetic variation.

Graphical abstract: Reconstructing and analysing cellular states, space and time from gene expression profiles of many cells and single cells
From the themed collection: 10th Anniversary of Molecular BioSystems
Review Article

Metabolomics – the complementary field in systems biology: a review on obesity and type 2 diabetes

This paper highlights the metabolomic roles in systems biology towards the elucidation of metabolic mechanisms in obesity and type 2 diabetes.

Graphical abstract: Metabolomics – the complementary field in systems biology: a review on obesity and type 2 diabetes
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Review Article

Systems biology approach to understanding post-traumatic stress disorder

This review paper presents known biological facts about PTSD and the mathematical/systems biology tools used to understand the underpinning molecular principles.

Graphical abstract: Systems biology approach to understanding post-traumatic stress disorder
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Review Article

Applications of mass spectrometry for cellular lipid analysis

We present the principles, advantages, and possible limitations of ESI and MALDI mass spectrometry-based methodologies for the analysis of lipid species.

Graphical abstract: Applications of mass spectrometry for cellular lipid analysis
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Review Article

Cysteine-mediated redox signalling in the mitochondria

This review represents a novel look at the many sources, cysteine targets, and signaling processes of ROS in the mitochondria.

Graphical abstract: Cysteine-mediated redox signalling in the mitochondria
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Review Article

Fatty acid biosynthesis revisited: structure elucidation and metabolic engineering

Fatty acids are primary metabolites synthesized by complex, elegant, and essential biosynthetic machinery.

Graphical abstract: Fatty acid biosynthesis revisited: structure elucidation and metabolic engineering
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Review Article

Evolution of the CRISPR-Cas adaptive immunity systems in prokaryotes: models and observations on virus–host coevolution

Mathematical modeling of the coevolution of CRISPR-Cas, the prokaryotic heritable adaptive immunity system, with viruses yields many non-trivial, testable predictions.

Graphical abstract: Evolution of the CRISPR-Cas adaptive immunity systems in prokaryotes: models and observations on virus–host coevolution
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Communication

A pre-structured helix in the intrinsically disordered 4EBP1

The eIF4E–binding protein 1 (4EBP1) has long been known to be completely unstructured without any secondary structures. We show here that it contains a pre-structured helix that presages the eIF4E-bound helix.

Graphical abstract: A pre-structured helix in the intrinsically disordered 4EBP1
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

Potential of serum metabolites for diagnosing post-stroke cognitive impairment

A panel of serum metabolite markers (glutamine, kynurenine, and LysoPC(18:2)) was identified as candidate diagnostic biomarkers for post-stroke cognitive impairment.

Graphical abstract: Potential of serum metabolites for diagnosing post-stroke cognitive impairment
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Open Access Paper

Characterisation of SEQ0694 (PrsA/PrtM) of Streptococcus equi as a functional peptidyl-prolyl isomerase affecting multiple secreted protein substrates

We present the first direct evidence that a streptococcal parvulin lipoprotein has PPIase activity, which likely affects virulence factor secretion.

Graphical abstract: Characterisation of SEQ0694 (PrsA/PrtM) of Streptococcus equi as a functional peptidyl-prolyl isomerase affecting multiple secreted protein substrates
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

Engineering chemically modified viruses for prostate cancer cell recognition

Viruses wrapped with peptide ligand-functionalized PEG allowed differentiation of biomarker levels on prostate cancer cells distinguishing disease aggressiveness.

Graphical abstract: Engineering chemically modified viruses for prostate cancer cell recognition
From the themed collection: Chemical Biology in Molecular BioSystems
Paper

The effect of sequence context on the activity of cytosine DNA glycosylases

We have examined how sequence context affects the ability of (N204D:L272A) mutants of uracil DNA glycosylase to cleave CX mismatches.

Graphical abstract: The effect of sequence context on the activity of cytosine DNA glycosylases
From the themed collection: Chemical Biology in Molecular BioSystems
Paper

A cross-cancer differential co-expression network reveals microRNA-regulated oncogenic functional modules

MicroRNAs (miRNAs) are small non-coding RNAs that can regulate their target gene expressions at the post-transcriptional level.

Graphical abstract: A cross-cancer differential co-expression network reveals microRNA-regulated oncogenic functional modules
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

Spatiotemporal-specific lncRNAs in the brain, colon, liver and lung of macaque during development

Identification of spatiotemporal-specific lncRNAs during the development of multiple tissues in rhesus.

Graphical abstract: Spatiotemporal-specific lncRNAs in the brain, colon, liver and lung of macaque during development
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

An integrated network platform for contextual prioritization of drugs and pathways

Network-based analyses facilitate contextual drug repositioning.

Graphical abstract: An integrated network platform for contextual prioritization of drugs and pathways
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

Systems biology-based discovery of a potential Atg4B agonist (Flubendazole) that induces autophagy in breast cancer

The aim of this study was to explore the autophagy-related protein 4B(ATG4B) and its targeted candidate agonist in triple-negative breast cancer (TNBC) therapy.

Graphical abstract: Systems biology-based discovery of a potential Atg4B agonist (Flubendazole) that induces autophagy in breast cancer
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

Integrated in silico and experimental methods revealed that Arctigenin inhibited angiogenesis and HCT116 cell migration and invasion through regulating the H1F4A and Wnt/β-catenin pathway

The proteomic analysis integrated signalling network analysis suggested that the Wnt/β-catenin signalling pathway was a novel target of Arctigenin.

Graphical abstract: Integrated in silico and experimental methods revealed that Arctigenin inhibited angiogenesis and HCT116 cell migration and invasion through regulating the H1F4A and Wnt/β-catenin pathway
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

In silico spatial simulations reveal that MCC formation and excess BubR1 are required for tight inhibition of the anaphase-promoting complex

In response to the activation of the mitotic spindle assembly checkpoint (SAC), distinct inhibitory pathways control the activity of the anaphase-promoting complex (APC/C).

Graphical abstract: In silico spatial simulations reveal that MCC formation and excess BubR1 are required for tight inhibition of the anaphase-promoting complex
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

Protein–protein interactions generate hidden feedback and feed-forward loops to trigger bistable switches, oscillations and biphasic dose–responses

Our work reveals that simple reversible protein–protein interactions, when embedded into signalling cascades, give rise to extremely rich and complex regulatory dynamics in the absence of explicit positive and negative feedbacks.

Graphical abstract: Protein–protein interactions generate hidden feedback and feed-forward loops to trigger bistable switches, oscillations and biphasic dose–responses
From the themed collection: 10th Anniversary of Molecular BioSystems
Open Access Paper

Exploration of the HIF-1α/p300 interface using peptide and Adhiron phage display technologies

A range of experimental approaches are used to understand the HIF-1α/p300 interface – an important anticancer drug development target – in greater detail.

Graphical abstract: Exploration of the HIF-1α/p300 interface using peptide and Adhiron phage display technologies
From the themed collection: Chemical Biology in Molecular BioSystems
Paper

A genetically amenable platensimycin- and platencin-overproducer as a platform for biosynthetic explorations: a showcase of PtmO4, a long-chain acyl-CoA dehydrogenase

Platensimycin and platencin congeners from overproducing strains support PtmO4 as a long-chain acyl-CoA dehydrogenase catalyzing β-oxidation of the diterpenoid intermediates.

Graphical abstract: A genetically amenable platensimycin- and platencin-overproducer as a platform for biosynthetic explorations: a showcase of PtmO4, a long-chain acyl-CoA dehydrogenase
From the themed collection: 10th Anniversary of Molecular BioSystems
Paper

Synthetic small molecules that induce neuronal differentiation in neuroblastoma and fibroblast cells

Imidazole-based synthetic small molecules promote neurogenesis in readily available and simply manageable neuroblastoma and fibroblast cells.

Graphical abstract: Synthetic small molecules that induce neuronal differentiation in neuroblastoma and fibroblast cells
From the themed collection: Chemical Biology in Molecular BioSystems
Paper

Probing the effect of an inhibitor of an ATPase domain of Hsc70 on clathrin-mediated endocytosis

Az blocks the association of Hsc70 with clathrin and consequently suppresses the disassembly of CCVs during clathrin-mediated endocytosis.

Graphical abstract: Probing the effect of an inhibitor of an ATPase domain of Hsc70 on clathrin-mediated endocytosis
From the themed collection: Chemical Biology in Molecular BioSystems
Paper

Division time-based amplifiers for stochastic gene expression

While cell-to-cell variability is a phenotypic consequence of gene expression noise, sources of this noise may be complex – apart from intrinsic sources such as the random birth/death of mRNA and stochastic switching between promoter states, there are also extrinsic sources of noise such as cell division where division times are either constant or random.

Graphical abstract: Division time-based amplifiers for stochastic gene expression
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

Metabolomics identifies the intersection of phosphoethanolamine with menaquinone-triggered apoptosis in an in vitro model of leukemia

We characterize the anti-proliferative activity of menaquinone in a leukemia cell line and use metabolomics to link it to phosphoethanolamine.

Graphical abstract: Metabolomics identifies the intersection of phosphoethanolamine with menaquinone-triggered apoptosis in an in vitro model of leukemia
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

In silico study of VP35 inhibitors: from computational alanine scanning to essential dynamics

Ligands binding significantly affect protein flexibility and dynamics.

Graphical abstract: In silico study of VP35 inhibitors: from computational alanine scanning to essential dynamics
From the themed collection: Chemical Biology in Molecular BioSystems
Paper

Structural D/E-rich repeats play multiple roles especially in gene regulation through DNA/RNA mimicry

D/E-rich proteins might be involved in DNA mimicry, mRNA processing and regulation of the transcription complex.

Graphical abstract: Structural D/E-rich repeats play multiple roles especially in gene regulation through DNA/RNA mimicry
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

Sequential myosin phosphorylation activates tarantula thick filament via a disorder–order transition

Tarantula thick filament activation is triggered by disorder-to-order transition in myosin regulatory light chain N-terminal extension controlled by sequential phosphorylation.

Graphical abstract: Sequential myosin phosphorylation activates tarantula thick filament via a disorder–order transition
From the themed collection: Chemical Biology in Molecular BioSystems
Paper

Multiscale characterization of ageing and cancer progression by a novel network entropy measure

We characterize cancer and ageing cell states with a multiscale network entropy approach, measuring “parameter space” available to the cell.

Graphical abstract: Multiscale characterization of ageing and cancer progression by a novel network entropy measure
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

Effects of culture media on metabolic profiling of the human gastric cancer cell line SGC7901

Culture media significantly affect cellular metabolic profiling.

Graphical abstract: Effects of culture media on metabolic profiling of the human gastric cancer cell line SGC7901
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

High-resolution structural characterization of Noxa, an intrinsically disordered protein, by microsecond molecular dynamics simulations

Microsecond molecular dynamics simulations reveal structural and functional features of Noxa, an intrinsically disordered protein, at atomic-level resolution.

Graphical abstract: High-resolution structural characterization of Noxa, an intrinsically disordered protein, by microsecond molecular dynamics simulations
From the themed collection: Chemical Biology in Molecular BioSystems
Paper

Design principles of a conditional futile cycle exploited for regulation

Activation of a regulatory protein by interruption of a futile cycle involves a trade-off between response time and energy expenditure.

Graphical abstract: Design principles of a conditional futile cycle exploited for regulation
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

Variability assessment of 15N metabolic labeling-based proteomics workflow in mouse plasma and brain

Repeatability of the 15N metabolic labeling workflow for quantitative proteomics in mouse plasma and brain specimens.

Graphical abstract: Variability assessment of 15N metabolic labeling-based proteomics workflow in mouse plasma and brain
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

Early markers of Fabry disease revealed by proteomics

Discovery of early urinary biomarkers for Fabry disease in male and female adult patients revealed by proteomics.

Graphical abstract: Early markers of Fabry disease revealed by proteomics
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Open Access Paper

Probing the effect of minor groove interactions on the catalytic efficiency of DNAzymes 8–17 and 10–23

An adenosine analog devoid of the N3-nitrogen of the purine ring was incorporated into the catalytic cores of the well-known DNA enzymes 8–17 and 10–23. The results show that minor groove interactions are important for the catalytic activity and thus constitute an important feature of DNA enzymes.

Graphical abstract: Probing the effect of minor groove interactions on the catalytic efficiency of DNAzymes 8–17 and 10–23
From the themed collection: Chemical Biology in Molecular BioSystems
Open Access Paper

Production of indole antibiotics induced by exogenous gene derived from sponge metagenomes

Sponge metagenomes are accessible genetic sources containing genes and gene clusters responsible for the biosynthesis of sponge-derived bioactive natural products.

Graphical abstract: Production of indole antibiotics induced by exogenous gene derived from sponge metagenomes
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Open Access Paper

The distribution pattern of genetic variation in the transcript isoforms of the alternatively spliced protein-coding genes in the human genome

The relationships among the types of transcripts, the classes of coding SNPs and the population frequencies in the human genome.

Graphical abstract: The distribution pattern of genetic variation in the transcript isoforms of the alternatively spliced protein-coding genes in the human genome
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

Synthetic artificial microRNAs targeting UCA1-MALAT1 or c-Myc inhibit malignant phenotypes of bladder cancer cells T24 and 5637

We provided a platform for constructing artificial microRNAs that can silence both protein-coding genes and non-coding genes.

Graphical abstract: Synthetic artificial microRNAs targeting UCA1-MALAT1 or c-Myc inhibit malignant phenotypes of bladder cancer cells T24 and 5637
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

Integrative analysis of lung development–cancer expression associations reveals the roles of signatures with inverse expression patterns

Integrative analysis of lung development–cancer expression patterns reveals that proliferation and immunity were involved in the inverse expression patterns.

Graphical abstract: Integrative analysis of lung development–cancer expression associations reveals the roles of signatures with inverse expression patterns
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Open Access Paper

Selection of LNA-containing DNA aptamers against recombinant human CD73

Aptamers containing LNA nucleotides were selected against recombinant human CD73 using SELEX and next generation sequencing (NGS) with custom NGS bioinformatics software (BION-apta).

Graphical abstract: Selection of LNA-containing DNA aptamers against recombinant human CD73
From the themed collection: Chemical Biology in Molecular BioSystems
Paper

Hierarchical control of coherent gene clusters defines the molecular mechanisms of glioblastoma

We report an integrative networks-based analysis to identify a system of coherent gene modules in primary and secondary glioblastoma.

Graphical abstract: Hierarchical control of coherent gene clusters defines the molecular mechanisms of glioblastoma
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

Cancer-associated fibroblasts induce trastuzumab resistance in HER2 positive breast cancer cells

CAFs isolated from HER2+ patients secreted higher levels of IL6 which expanded cancer stem cells and activated multiple pathways, then induced trastuzumab resistance in HER2 positive breast cancer cells.

Graphical abstract: Cancer-associated fibroblasts induce trastuzumab resistance in HER2 positive breast cancer cells
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

Mathematical modeling of the apo and holo transcriptional regulation in Escherichia coli

Transcription factors can bind to DNA either with their effector bound (holo conformation), or as free proteins (apo conformation).

Graphical abstract: Mathematical modeling of the apo and holo transcriptional regulation in Escherichia coli
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

An integrated analysis of differential miRNA and mRNA expressions in human gallstones

An integrated analysis of differential miRNA and mRNA expressions firstly revealed that miR-210 and its target ATP11A may involve in the ABC-transporters pathway, which contribute to gallstone formation.

Graphical abstract: An integrated analysis of differential miRNA and mRNA expressions in human gallstones
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

Insights into the binding modes of CC chemokine receptor 4 (CCR4) inhibitors: a combined approach involving homology modelling, docking, and molecular dynamics simulation studies

CC chemokine receptor 4 (CCR4), a G protein-coupled receptor (GPCR), plays a vital role in the progression of asthma, T-cell lymphoma, inflammation, and Alzheimer's disease.

Graphical abstract: Insights into the binding modes of CC chemokine receptor 4 (CCR4) inhibitors: a combined approach involving homology modelling, docking, and molecular dynamics simulation studies
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

Investigating correlations in the altered metabolic profiles of obese and diabetic subjects in a South Indian Asian population using an NMR-based metabolomic approach

It is well known that obesity/high body mass index (BMI) plays a key role in the evolution of insulin resistance and type-2 diabetes mellitus (T2DM).

Graphical abstract: Investigating correlations in the altered metabolic profiles of obese and diabetic subjects in a South Indian Asian population using an NMR-based metabolomic approach
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

Prediction of advanced ovarian cancer recurrence by plasma metabolic profiling

Plasma metabolic profiling yielded a panel of prognostic biomarkers, which strongly predicted ovarian cancer recurrence and could potentially shape individualized treatments in the future.

Graphical abstract: Prediction of advanced ovarian cancer recurrence by plasma metabolic profiling
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

Modeling the mitotic regulatory network identifies highly efficient anti-cancer drug combinations

A mammalian cell mitotic network model was built and two effective anti-cancer drug combinations, Aurora B/PLK1 and microtubule formation/PLK1, were identified.

Graphical abstract: Modeling the mitotic regulatory network identifies highly efficient anti-cancer drug combinations
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

A metabolomic and pharmacokinetic study on the mechanism underlying the lipid-lowering effect of orally administered berberine

The turnover of bile acids was involved in the lipid lowering effect of orally administered berberine.

Graphical abstract: A metabolomic and pharmacokinetic study on the mechanism underlying the lipid-lowering effect of orally administered berberine
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

UHPLC-LTQ-Orbitrap MS combined with spike-in method for plasma metabonomics analysis of acute myocardial ischemia rats and pretreatment effect of Danqi Tongmai tablet

Metabonomics analysis revealed the presumable pathological processes in the early stages of AMI and provided useful information on the pretreatment efficacy of DQTM.

Graphical abstract: UHPLC-LTQ-Orbitrap MS combined with spike-in method for plasma metabonomics analysis of acute myocardial ischemia rats and pretreatment effect of Danqi Tongmai tablet
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

Temporal-logic analysis of microglial phenotypic conversion with exposure to amyloid-β

Computational analysis using temporal logic shows how brain microglia could switch between phenotypes in response to amyloid-β or cytokines.

Graphical abstract: Temporal-logic analysis of microglial phenotypic conversion with exposure to amyloid-β
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

Studies of N9-arenthenyl purines as novel DFG-in and DFG-out dual Src/Abl inhibitors using 3D-QSAR, docking and molecular dynamics simulations

Recently, the development of Src/Abl (c-Src/Bcr–Abl tyrosine kinases) dual inhibitors has attracted considerable attention from the research community for the treatment of malignancies.

Graphical abstract: Studies of N9-arenthenyl purines as novel DFG-in and DFG-out dual Src/Abl inhibitors using 3D-QSAR, docking and molecular dynamics simulations
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

Identification of cancer-related lncRNAs through integrating genome, regulome and transcriptome features

A computational method for identifying cancer-related lncRNAs by integrating data from the genome, regulome and transcriptome.

Graphical abstract: Identification of cancer-related lncRNAs through integrating genome, regulome and transcriptome features
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

CIP2A regulates cancer metabolism and CREB phosphorylation in non-small cell lung cancer

Overexpression of CIP2A in lung cancer increased lactate production and CREB phosphorylation but decreased H2O2 production.

Graphical abstract: CIP2A regulates cancer metabolism and CREB phosphorylation in non-small cell lung cancer
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

Molecular dynamics-based discovery of novel phosphodiesterase-9A inhibitors with non-pyrazolopyrimidinone scaffolds

Via molecular dynamics-based virtual screening, 15 novel phosphodiesterase-9A inhibitors with five non-pyrazolopyrimidinone scaffolds were discovered.

Graphical abstract: Molecular dynamics-based discovery of novel phosphodiesterase-9A inhibitors with non-pyrazolopyrimidinone scaffolds
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Paper

Systems biosynthesis of secondary metabolic pathways within the oral human microbiome member Streptococcus mutans

Metabolomic profiling, systems exploration of the biosynthesis and immunomodulatory activities of hybrid human microbiome-derived nonribosomal peptide–polyketides, mutanobactins, from Streptococcus mutans.

Graphical abstract: Systems biosynthesis of secondary metabolic pathways within the oral human microbiome member Streptococcus mutans
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Method

iSBatch: a batch-processing platform for data analysis and exploration of live-cell single-molecule microscopy images and other hierarchical datasets

iSBatch: an ImageJ plugin for fast evaluation of analysis pipelines and visual exploration of datasets.

Graphical abstract: iSBatch: a batch-processing platform for data analysis and exploration of live-cell single-molecule microscopy images and other hierarchical datasets
From the themed collection: 10th Anniversary of Molecular BioSystems
Method

Improved metabolite profile smoothing for flux estimation

We develop several methods to improve the estimation of metabolite concentrations and accumulation fluxes from noisy time-course data, including use of a sigmoidal impulse function and a resampling-based approach.

Graphical abstract: Improved metabolite profile smoothing for flux estimation
From the themed collection: 2015 Hot Articles in Molecular BioSystems
Method

Computational characterization of parallel dimeric and trimeric coiled-coils using effective amino acid indices

RFCoil is a novel predictor for parallel coiled-coil dimer and trimer.

Graphical abstract: Computational characterization of parallel dimeric and trimeric coiled-coils using effective amino acid indices
From the themed collection: 2015 Hot Articles in Molecular BioSystems
59 items

About this collection

This on-going collection features all the articles published in Molecular BioSystems in 2015 highlighted by the reviewers of the articles as being particularly interesting or particularly significant research. Congratulations to all the authors whose articles are featured!

When articles are added to this collection they will be free to access for 4 weeks.

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