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Gene Expression of Caenorhabditis elegans Neurons Carries Information on Their Synaptic Connectivity
The claim that genetic properties of neurons significantly influence their synaptic network structure is a common notion in neuroscience. The nematode Caenorhabditis elegans provides an exciting opportunity to approach this question in a large-scale quantitative manner. Its synaptic connectivity…
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Mammalian Small Nucleolar RNAs Are Mobile Genetic Elements
Small nucleolar RNAs (snoRNAs) of the H/ACA box and C/D box categories guide the pseudouridylation and the 2′-O-ribose methylation of ribosomal RNAs by forming short duplexes with their target. Similarly, small Cajal body–specific RNAs (scaRNAs) guide modifications of spliceosomal RNAs. The vast…
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Drosophila SPF45: A Bifunctional Protein with Roles in Both Splicing and DNA Repair
The sequence of the SPF45 protein is significantly conserved, yet functional studies have identified it as a splicing factor in animal cells and as a DNA-repair protein in plants. Using a combined genetic and biochemical approach to investigate this apparent functional discrepancy, we unify and…
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Three Drug Combinations for Late-Stage Trypanosoma brucei gambiense Sleeping Sickness: A Randomized Clinical Trial in Uganda
Objectives: Our objective was to compare the efficacy and safety of three drug combinations for the treatment of late-stage human African trypanosomiasis caused by Trypanosoma brucei gambiense. Design: This trial was a randomized, open-label, active control, parallel clinical trial comparing three…
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On Side-Chain Conformational Entropy of Proteins
The role of side-chain entropy (SCE) in protein folding has long been speculated about but is still not fully understood. Utilizing a newly developed Monte Carlo method, we conducted a systematic investigation of how the SCE relates to the size of the protein and how it differs among a protein's…
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Cross-Talk with Myeloid Accessory Cells Regulates Human Natural Killer Cell Interferon-γ Responses to Malaria
Data from a variety of experimental models suggest that natural killer (NK) cells require signals from accessory cells in order to respond optimally to pathogens, but the precise identity of the cells able to provide such signals depends upon the nature of the infectious organism. Here we show that…
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Palladin Mutation Causes Familial Pancreatic Cancer and Suggests a New Cancer Mechanism
Background: Pancreatic cancer is a deadly disease. Discovery of the mutated genes that cause the inherited form(s) of the disease may shed light on the mechanism(s) of oncogenesis. Previously we isolated a susceptibility locus for familial pancreatic cancer to chromosome location 4q32–34. In this…
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Balancing Robustness and Evolvability
Can a single unifying mathematical framework help to explain robustness - the ability of organisms to persist in the face of changing conditions - at all biological scales, from biochemical to ecological?
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How Bacterial Communities Expand Functional Repertoires
Probiotics, live microorganisms administered to improve health, interact in as yet poorly understood ways with the complex microbial communities that inhabit the human host.
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Correction: A Signaling Network for Patterning of Neuronal Connectivity in the Drosophila Brain
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What Is the Hobbit?
The tiny hominid bones, which a joint Australian-Indonesian team unearthed in 2003 on the Indonesian island of Flores, have quickly become as celebrated (and derided) as any find in the tempestuous history of human paleontology.
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Impaired Genome Maintenance Suppresses the Growth Hormone–Insulin-Like Growth Factor 1 Axis in Mice with Cockayne Syndrome
Cockayne syndrome (CS) is a photosensitive, DNA repair disorder associated with progeria that is caused by a defect in the transcription-coupled repair subpathway of nucleotide excision repair (NER). Here, complete inactivation of NER in Csbm/m/Xpa−/− mutants causes a phenotype that reliably mimics…
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Impact of Extended-Duration Shifts on Medical Errors, Adverse Events, and Attentional Failures
Background: A recent randomized controlled trial in critical-care units revealed that the elimination of extended-duration work shifts (≥24 h) reduces the rates of significant medical errors and polysomnographically recorded attentional failures. This raised the concern that the extended-duration…
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TV Viewing and Physical Activity Are Independently Associated with Metabolic Risk in Children: The European Youth Heart Study
Background: TV viewing has been linked to metabolic-risk factors in youth. However, it is unclear whether this association is independent of physical activity (PA) and obesity. Methods and Findings: We did a population-based, cross-sectional study in 9- to 10-y-old and 15- to 16-y-old boys and…
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Impaired Hepatitis C Virus-Specific T Cell Responses and Recurrent Hepatitis C Virus in HIV Coinfection
Background: Hepatitis C virus (HCV)-specific T cell responses are critical for spontaneous resolution of HCV viremia. Here we examined the effect of a lymphotropic virus, HIV-1, on the ability of coinfected patients to maintain spontaneous control of HCV infection. Methods and Findings: We measured…
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Are Residents' Extended Shifts Associated With Adverse Events?
Szklo-Coxe discusses a new prospective study in PLoS Medicine that examined the relationship between residents' work patterns and adverse clinical events.
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TV and Inactivity Are Separate Contributors to Metabolic Risk Factors in Children
Interventions against childhood obesity will need to target both excess TV viewing and physical inactivity "separately, yet together," say Prentice and Jebb.
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Computational Reconstruction of Iron- and Manganese-Responsive Transcriptional Networks in α-Proteobacteria
We used comparative genomics to investigate the distribution of conserved DNA-binding motifs in the regulatory regions of genes involved in iron and manganese homeostasis in alpha-proteobacteria. Combined with other computational approaches, this allowed us to reconstruct the metal regulatory…
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Soft Sweeps III: The Signature of Positive Selection from Recurrent Mutation
Polymorphism data can be used to identify loci at which a beneficial allele has recently gone to fixation, given that an accurate description of the signature of selection is available. In the classical model that is used, a favored allele derives from a single mutational origin. This ignores the…
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