PLP and GABA trigger GabR-mediated transcription regulation in via external aldimine formation.

The protein regulator of the operon and its own gene (GabR) is a transcriptional activator that regulates transcription of γ-aminobutyric acid aminotransferase (GABA-AT; GabT) upon interactions with pyridoxal-5'-phosphate (PLP) and GABA, and thereby promotes the biosynthesis of glutamate from GABA. We show here that the external aldimine formed between PLP and GABA is apparently responsible for triggering the GabR-mediated transcription activation. Details of the "active site" in the structure of the GabR effector-binding/oligomerization (Eb/O) domain suggest that binding a monocarboxylic γ-amino acid such as GABA should be preferred over dicarboxylic acid ligands.

Correction to "Chiral Cyclohexane 1,3-Diones as Inhibitors of Mutant SOD1-Dependent Protein Aggregation for the Treatment of ALS".

[This corrects the article DOI: 10.1021/ml3000963.].

My femme friendship.

This autoethnographic study of femme friendship explores the connection and relationship between two femme lesbians-my femme friend Amber and myself. The shared experience of invisibility and the related perils and privileges that come with passing as straight enact a bond unlike any either of us have previously experienced. Meeting within the context of a polyamorous relationship adds a layer of complexity to our friendship that deepens the relationship.

Persistence of HIV drug resistance among South African children given nevirapine to prevent mother-to-child-transmission.

Objectives: We set out to examine the prevalence and persistence of mutations conferring high-level nonnucleoside reverse transcriptase (NNRTI)-resistance in a cohort of HIV-infected children who had failed prophylaxis to prevent mother-to-child-transmission (PMTCT).

Design: A prospective observational cohort study at the Pediatric HIV Clinic at Kalafong Provincial Tertiary Hospital in Pretoria, South Africa.

Methods: Children referred for initiation of antiretroviral therapy (ART) were enrolled from July 2010 through February 2013.

In vivo imaging of ocular blood flow using high-speed ultrasound.

Clinical ophthalmic ultrasound is currently performed with mechanically scanned, single-element probes, but these are unable to provide useful information about blood flow with Doppler techniques. Linear arrays are well-suited for the detection of blood flow, but commercial systems generally exceed FDA ophthalmic safety limits. A high-speed plane-wave ultrasound approach with an 18-MHz linear array was utilized to characterize blood flow in the orbit and choroid.

Multicenter study of cigarette smoking among adults with asthma exacerbations in the emergency department, 2011-2012.

Introduction: Previous studies demonstrated a high prevalence of cigarette smoking in patients presenting to the emergency department (ED) with acute asthma. Despite the clinical and public health importance, there have been no recent multicenter efforts to characterize this patient population. We aimed to update the prevalence of cigarette smoking among ED patients with asthma exacerbations.

Platform-Independent Cirrus and Spectralis Thickness Measurements in Eyes with Diabetic Macular Edema Using Fully Automated Software.

Purpose: We determine whether the automated segmentation software, Duke Optical Coherence Tomography Retinal Analysis Program (DOCTRAP), can measure, in a platform-independent manner, retinal thickness on Cirrus and Spectralis spectral domain optical coherence tomography (SD-OCT) images in eyes with diabetic macular edema (DME) under treatment in a clinical trial.

Methods: Automatic segmentation software was used to segment the internal limiting membrane (ILM), inner retinal pigment epithelium (RPE), and Bruch's membrane (BM) in SD-OCT images acquired by Cirrus and Spectralis commercial systems, from the same eye, on the same day during a clinical interventional DME trial. Mean retinal thickness differences were compared across commercial and DOCTRAP platforms using intraclass correlation (ICC) and Bland-Altman plots.

Sample size re-estimation and other midcourse adjustments with sequential parallel comparison design.

Sequential parallel comparison design (SPCD) was proposed to reduce placebo response in a randomized trial with placebo comparator. Subjects are randomized between placebo and drug in stage 1 of the trial, and then, placebo non-responders are re-randomized in stage 2. Efficacy analysis includes all data from stage 1 and all placebo non-responding subjects from stage 2.

Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication.

Coronaviruses are of veterinary and medical importance and include highly pathogenic zoonotic viruses, such as SARS-CoV and MERS-CoV. They are known to efficiently evade early innate immune responses, manifesting in almost negligible expression of type-I interferons (IFN-I). This evasion strategy suggests an evolutionary conserved viral function that has evolved to prevent RNA-based sensing of infection in vertebrate hosts.

Comparison of the American Joint Committee on Cancer Seventh Edition and Brigham and Women's Hospital Cutaneous Squamous Cell Carcinoma Tumor Staging in Immunosuppressed Patients.

Background: The American Joint Committee on Cancer 7th edition (AJCC-7) and Brigham and Women's Hospital (BWH) staging criteria for cutaneous squamous cell carcinoma (cSCC) have not been validated in immunosuppressed patients.

Objective: To compare the AJCC-7 and BWH staging systems for cSCCs in immunosuppressed patients.

Materials And Methods: A single-institution retrospective cohort study of cSCCs in immunosuppressed patients.

A Novel Strategy for Attenuating Opioid Withdrawal in Neonates.

The rate of Neonatal Abstinence Syndrome (NAS) has drastically increased over the past decade. The average hospital expense per NAS patient has tripled, while the number of babies born to opioid-dependent mothers has increased to 5 in 1000 births. Current treatment options are limited to opioid replacement and tapering.

Lineage A Betacoronavirus NS2 Proteins and the Homologous Torovirus Berne pp1a Carboxy-Terminal Domain Are Phosphodiesterases That Antagonize Activation of RNase L.

Viruses in the family , within the order , are etiologic agents of a range of human and animal diseases, including both mild and severe respiratory diseases in humans. These viruses encode conserved replicase and structural proteins as well as more diverse accessory proteins, encoded in the 3' ends of their genomes, that often act as host cell antagonists. We previously showed that 2',5'-phosphodiesterases (2',5'-PDEs) encoded by the prototypical , mouse hepatitis virus (MHV), and by Middle East respiratory syndrome-associated coronavirus antagonize the oligoadenylate-RNase L (OAS-RNase L) pathway.

How to Get Cost-Effectiveness Analysis Right? The Case of Vaccine Economics in Latin America.

Background: In middle-income countries, vaccines against pneumococcal disease, rotavirus, and human papilloma virus are in general more costly, not necessarily cost saving, and less consistently cost-effective than earlier generation vaccines against measles, diphtheria, tetanus, and pertussis. Budget impact is also substantial; public spending on vaccines in countries adopting new vaccines is, on average, double the amount of countries that have not adopted. Policymakers must weigh the costs and benefits of the adoption decision carefully, given the low coverage of other kinds of cost-effective health and nonhealth interventions in these same settings and relatively flat overall public spending on health as a share of gross domestic product (GDP) over time.

A Case Series of Complex Recalcitrant Wounds Treated with Epidermal Grafts Harvested from an Automated Device.

Introduction: Epidermal grafting has several advantages over full-thickness or split-thickness grafts in the treatment of complex non-healing wounds. These include the low risk of donor site complications, minimal patient discomfort, and abstention from the operating room. Traditionally, the lack of reliable epidermal harvesting techniques has limited its clinical utilization.

Combined tomography and epithelial thickness mapping for diagnosis of keratoconus.

Purpose: Scanning Scheimpflug provides information regarding corneal thickness and 2-surface topography while arc-scanned high-frequency ultrasound allows depiction of the epithelial and stromal thickness distributions. Both techniques are useful in detection of keratoconus. Our aim was to develop and test a keratoconus classifier combining information from both methods.

Focused ultrasound in ophthalmology.

The use of focused ultrasound to obtain diagnostically significant information about the eye goes back to the 1950s. This review describes the historical and technological development of ophthalmic ultrasound and its clinical application and impact. Ultrasound, like light, can be focused, which is crucial for formation of high-resolution, diagnostically useful images.

Use of negative pressure wound therapy on malignant wounds - a case report and review of literature.

The presence of malignancy is considered a contraindication to the use of negative pressure wound therapy (NPWT) because of concerns that it may promote tumourigenesis and expedite metastasis. This notion is extrapolated from studies evaluating NPWT in normal tissues. Despite the absence of direct evidence, the use of this technology in malignant wounds is widely considered a contraindication.

Word Adjacency Graph Modeling: Separating Signal From Noise in Big Data.

There is a need to develop methods to analyze Big Data to inform patient-centered interventions for better health outcomes. The purpose of this study was to develop and test a method to explore Big Data to describe salient health concerns of people with epilepsy. Specifically, we used Word Adjacency Graph modeling to explore a data set containing 1.

Targeting Bacterial Nitric Oxide Synthase with Aminoquinoline-Based Inhibitors.

Nitric oxide is produced in Gram-positive pathogens Bacillus anthracis and Staphylococcus aureus by the bacterial isoform of nitric oxide synthase (NOS). Inhibition of bacterial nitric oxide synthase (bNOS) has been identified as a promising antibacterial strategy for targeting methicillin-resistant S. aureus [Holden, J.

Design and Synthesis of Potent Quinazolines as Selective β-Glucocerebrosidase Modulators.

Gaucher's disease is a common genetic disease caused by mutations in the β-glucocerebrosidase (GBA1) gene that have been also linked to increased risk of Parkinson's disease and Lewy body dementia. Stabilization of misfolded mutant β-glucocerebrosidase (GCase) represents an important therapeutic strategy in synucleinopathies. Here we report a novel class of GCase quinazoline inhibitors, obtained in a high throughput screening, with moderate potency against wild-type GCase.

Acellular dermal matrix reduces capsule formation in two-stage breast reconstruction.

Acellular dermal matrix (ADM) is commonly employed to create an inferior pocket for the tissue expander in two-stage breast reconstruction. The authors sought to determine whether placement of ADM during the first stage of reconstruction decreases the amount of capsule formation at implant exchange. Patients who underwent mastectomy and tissue expander reconstruction were included in this study.

Ultrafast Ultrasound Imaging of Ocular Anatomy and Blood Flow.

Purpose: Ophthalmic ultrasound imaging is currently performed with mechanically scanned single-element probes. These probes have limited capabilities overall and lack the ability to image blood flow. Linear-array systems are able to detect blood flow, but these systems exceed ophthalmic acoustic intensity safety guidelines.