Author Correction: Discovery of stimulation-responsive immune enhancers with CRISPR activation.

In this Letter, analysis of steady-state regulatory T (Treg) cell percentages from Il2ra enhancer deletion (EDEL) and wild-type (WT) mice revealed no differences between them (Extended Data Fig. 9d). This analysis included two mice whose genotypes were incorrectly assigned.

Measuring behavioral thermal tolerance to address hot topics in ecology, evolution, and conservation.

Understanding the impacts of anthropogenic climate change requires knowing how animals avoid heat stress, and the consequences of failing to do so. Animals primarily use behavior to avoid overheating, but biologists' means for measuring and interpreting behavioral signs of stress require more development. Herein, we develop the measurement of behavioral thermal tolerance using four species of lizards.

Discovery of stimulation-responsive immune enhancers with CRISPR activation.

The majority of genetic variants associated with common human diseases map to enhancers, non-coding elements that shape cell-type-specific transcriptional programs and responses to extracellular cues. Systematic mapping of functional enhancers and their biological contexts is required to understand the mechanisms by which variation in non-coding genetic sequences contributes to disease. Functional enhancers can be mapped by genomic sequence disruption, but this approach is limited to the subset of enhancers that are necessary in the particular cellular context being studied.

Enhancing homology-directed genome editing by catalytically active and inactive CRISPR-Cas9 using asymmetric donor DNA.

Targeted genomic manipulation by Cas9 can efficiently generate knockout cells and organisms via error-prone nonhomologous end joining (NHEJ), but the efficiency of precise sequence replacement by homology-directed repair (HDR) is substantially lower. Here we investigate the interaction of Cas9 with target DNA and use our findings to improve HDR efficiency. We show that dissociation of Cas9 from double-stranded DNA (dsDNA) substrates is slow (lifetime ∼6 h) but that, before complete dissociation, Cas9 asymmetrically releases the 3' end of the cleaved DNA strand that is not complementary to the sgRNA (nontarget strand).

Daclatasvir plus Sofosbuvir for HCV in Patients Coinfected with HIV-1.

Background: The combination of daclatasvir, a hepatitis C virus (HCV) NS5A inhibitor, and the NS5B inhibitor sofosbuvir has shown efficacy in patients with HCV monoinfection. Data are lacking on the efficacy and safety of this combination in patients coinfected with human immunodeficiency virus type 1 (HIV-1).

Methods: This was an open-label study involving 151 patients who had not received HCV treatment and 52 previously treated patients, all of whom were coinfected with HIV-1.

Priapism induced by boceprevir-CYP3A4 inhibition and α-adrenergic blockade: case report.

A 44-year-old white man presented to the emergency department with a 3-day history of priapism requiring a surgically performed distal penile shunt. A drug-drug interaction is the suspected cause whereby CYP3A4 inhibition by boceprevir led to increased exposures of doxazosin, tamsulosin, and/or quetiapine, resulting in additional α-adrenergic blockade.

A year to remember. Interview by Lynne Pearce.

Since being named Nursing Standard's 2009 nurse of the year, Lin Graham-Ray has worked hard to raise the profile of looked-after children.

Viscous contact lens system for vitrectomy.

The authors describe a recently developed system for use in vitreoretinal surgery. The system is compatible with a variety of lens choices, including wide-field, equatorial, and high-magnification direct viewing lenses, allowing for visualization of the far peripheral retina and detailed imaging of the macula. Used with autoclavable lenses, the system achieves high-resolution image quality at a cost-effective price.

Phenotypic and functional characterization of HIV-1-specific CD4+CD8+ double-positive T cells in early and chronic HIV-1 infection.

Objective: CD4+CD8+ double-positive (DP) T cells represent a poorly characterized population of effector T cells found at low frequencies in the peripheral blood. Virus-specific DP T cells have been identified in HIV-1-infected patients but their origin, relationship to conventional CD4+ and CD8+ single-positive (SP) T cells, and role in disease pathogenesis are unclear.

Methods: In this study, peripheral blood T cells were analyzed for cytokine production, maturation, and cytolytic marker expression by polychromatic flow cytometry in subjects with both early (n = 27) and chronic (n = 21) HIV-1 infection.

CTL fail to accumulate at sites of HIV-1 replication in lymphoid tissue.

The inability of HIV-1-specific CTL to fully suppress virus replication as well as the failure of administration of exogenous CTL to lower viral loads are not understood. To evaluate the hypothesis that these phenomena are due to a failure of CTL to localize at sites of HIV-1 replication, we assessed the distribution of HIV-1 RNA and HIV-1-specific CTL identified by HIV-1 peptide/HLA class I tetrameric complexes (tetramers) within lymph nodes of 14 HIV-1-infected individuals who were not receiving antiretroviral therapy. A median of 0.

Regimen simplification to atazanavir-ritonavir alone as maintenance antiretroviral therapy after sustained virologic suppression.

Context: The long-term adverse effects, expense, and difficulty of adherence to antiretroviral regimens have led to studies of simpler maintenance therapies. Maintenance therapy with ritonavir-boosted atazanavir alone is a possible option because of low pill burden, once-daily dosing, safety, and unique resistance profile.

Objective: To assess whether simplified maintenance therapy with atazanavir-ritonavir alone after virologic suppression increases the risk of virologic failure (2 consecutive human immunodeficiency virus type 1 [HIV-1] RNA measurements of > or =200 copies/mL).