Pathogen-specific DNA sensing with engineered zinc finger proteins immobilized on a polymer chip.

A specific double-stranded DNA sensing system is of great interest for diagnostic and other biomedical applications. Zinc finger domains, which recognize double-stranded DNA, can be engineered to form custom DNA-binding proteins for the recognition of specific DNA sequences. As a proof of concept, a sequence-enabled reassembly of a TEM-1 β-lactamase system (SEER-LAC) was previously demonstrated to develop zinc finger protein (ZFP) arrays for the detection of a double-stranded bacterial DNA sequence.

Therapeutic Effects of a TANK-Binding Kinase 1 Inhibitor in Germinal Center-Driven Collagen-Induced Arthritis.

Objective: The production of class-switched high-affinity autoantibodies derived from organized germinal centers (GCs) is a hallmark of many autoimmune inflammatory diseases, including rheumatoid arthritis (RA). TANK-binding kinase 1 (TBK-1) is a serine/threonine kinase involved in the maturation of GC follicular helper T (Tfh) cells downstream of inducible costimulator signaling. We undertook this study to assess the therapeutic potential of TBK-1 inhibition using the small-molecule inhibitor WEHI-112 in antibody-dependent models of inflammatory arthritis.

Use of Head Computed Tomography (CT) in the Pediatric Emergency Department in Evaluation of Children With New-Onset Afebrile Seizure.

Objective: Cranial computed tomography (CT) is not recommended in the routine evaluation of children with first afebrile seizure due to its low yield. The objective was to assess the current practice in our pediatric emergency department regarding the use of head CT in children with first afebrile seizure and to identify the factors that lead to ordering a head CT.

Methods: Medical records of patients between 1 month and 18 years old evaluated at our emergency department for presentation of first afebrile seizure between 2010 and 2014 were retrospectively reviewed.

Rosmarinic Acid Restores Complete Transparency of Sonicated Human Cataract Ex Vivo and Delays Cataract Formation In Vivo.

Cataract, the leading cause of vision impairment worldwide, arises from abnormal aggregation of crystallin lens proteins. Presently, surgical removal is the only therapeutic approach. Recent findings have triggered renewed interest in development of non-surgical treatment alternatives.

Current fluctuations in quantum absorption refrigerators.

Absorption refrigerators transfer thermal energy from a cold bath to a hot bath without input power by utilizing heat from an additional "work" reservoir. Particularly interesting is a three-level design for a quantum absorption refrigerator, which can be optimized to reach the maximal (Carnot) cooling efficiency. Previous studies of three-level chillers focused on the behavior of the averaged cooling current.

Outpatient and Inpatient Single-level Cervical Total Disc Replacement: A Comparison of 30-day Outcomes.

Study Design: A retrospective cohort study.

Objective: The aim of this study was to compare 30-day postoperative outcomes between patients undergoing outpatient and inpatient single-level cervical total disc replacement (TDR) surgery.

Summary Of Background Data: Cervical TDR is a motion-sparing treatment for cervical radiculopathy and myelopathy.

The impact of prophylactic intraoperative vancomycin powder on microbial profile, antibiotic regimen, length of stay, and reoperation rate in elective spine surgery.

Background Context: There is growing concern that the microbial profile of surgical site infection (SSI) in the setting of prophylactic vancomycin powder may favor more resistant and uncommon organisms.

Purpose: To demonstrate the impact of prophylactic intraoperative vancomycin powder on microbial profile, antibiotic regimen, length of stay (LOS), and reoperation rate in spine surgical site infection.

Study Design And/or Setting: Retrospective cohort study.

Continuity Between DSM-5 Section II and III Personality Disorders in a Dutch Clinical Sample.

The goal of this study was to evaluate the continuity across the Section II personality disorders (PDs) and the proposed Section III model of PDs in the Diagnostic and Statistical Manual of Mental Disorders (5th ed. [DSM-5]; American Psychiatric Association, 2013a ). More specifically, we analyzed association between the DSM-5 Section III pathological trait facets and Section II PDs among 110 Dutch adults (M age = 35.

The impact of work-related stress on medication errors in Eastern Region Saudi Arabia.

Objective: To examine the relationship between overall level and source-specific work-related stressors on medication errors rate.

Design: A cross-sectional study examined the relationship between overall levels of stress, 25 source-specific work-related stressors and medication error rate based on documented incident reports in Saudi Arabia (SA) hospital, using secondary databases.

Setting: King Abdulaziz Hospital in Al-Ahsa, Eastern Region, SA.

The 5-Item Modified Frailty Index Is Predictive of 30-Day Postoperative Complications in Patients Undergoing Kyphoplasty Vertebral Augmentation.

Background: Vertebral compression fractures are the most common spine injury seen in elderly patients. Vertebral augmentation is considered a safe and effective treatment. The ability to predict outcomes based on comorbidities is lacking.

Author Correction: Methods for Scarless, Selection-Free Generation of Human Cells and Allele-Specific Functional Analysis of Disease-Associated SNPs and Variants of Uncertain Significance.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Integrating in vitro and in silico approaches to evaluate the "dual functionality" of palmatine chloride in inhibiting and disassembling Tau-derived VQIVYK peptide fibrils.

Background: Alzheimer's disease (AD) is the most common neurodegenerative disorder which is characterized by the deposits of intra-cellular tau protein and extra-cellular amyloid-β (Aβ) peptides in the human brain. Understanding the mechanism of protein aggregation and finding compounds that are capable of inhibiting its aggregation is considered to be highly important for disease therapy.

Methods: We used an in vitro High-Throughput Screening for the identification of potent inhibitors of tau aggregation using a proxy model; a highly aggregation-prone hexapeptide fragment VQIVYK derived from tau.

Low dose naltrexone for induction of remission in Crohn's disease.

Background: Crohn's disease is a transmural, relapsing inflammatory condition afflicting the digestive tract. Opioid signalling, long known to affect secretion and motility in the gut, has been implicated in the inflammatory cascade of Crohn's disease. Low dose naltrexone, an opioid antagonist, has garnered interest as a potential therapy.

Unexpected binding behaviors of bacterial Argonautes in human cells cast doubts on their use as targetable gene regulators.

Prokaryotic Argonaute proteins (pAgos) have been proposed as an alternative to the CRISPR/Cas9 platform for gene editing. Although Argonaute from Natronobacterium gregoryi (NgAgo) was recently shown unable to cleave genomic DNA in mammalian cells, the utility of NgAgo or other pAgos as a targetable DNA-binding platform for epigenetic editing has not been explored. In this report, we evaluated the utility of two prokaryotic Argonautes (NgAgo and TtAgo) as DNA-guided DNA-binding proteins.

Purified Protein Delivery to Activate an Epigenetically Silenced Allele in Mouse Brain.

The ability to activate or repress specific genes in the brain could have a tremendous impact for understanding and treating neurological disorders. Artificial transcription factors based on zinc finger, TALE, and CRISPR/Cas9 programmable DNA-binding platforms have been widely used to regulate the expression of specific genes in cultured cells, but their delivery into the brain represents a critical challenge to apply such tools in live animals. In previous work, we developed a purified, zinc finger-based artificial transcription factor that could be injected systemically, cross the blood-brain barrier, and alter expression of a specific gene in the brain of an adult mouse model of Angelman syndrome.

Targeted DNA demethylation of the genome using the human TET1 catalytic domain.

DNA methylation is an important epigenetic modification involved in gene regulation and transposable element silencing. Changes in DNA methylation can be heritable and, thus, can lead to the formation of stable epialleles. A well-characterized example of a stable epiallele in plants is , which consists of the loss of DNA cytosine methylation (5mC) in the promoter of the () gene, causing up-regulation of and a heritable late-flowering phenotype.

Mechanistic insights into remodeled Tau-derived PHF6 peptide fibrils by Naphthoquinone-Tryptophan hybrids.

Intra-cellular tau protein tangles and extra-cellular β-amyloid plaques are hallmarks of Alzheimer's disease (AD), characterized by the conversion of natively unfolded monomeric protein/peptide into misfolded β-sheet rich aggregates. Therefore, inhibiting the aggregation cascade or disassembling the pre-formed aggregates becomes a pivotal event in disease treatment. In the present study, we show that Naphthoquinone-Tryptophan hybrids, i.

Assessment of anaerobic biodegradation of bis(2-chloroethyl) ether in groundwater using carbon and chlorine compound-specific isotope analysis.

Carbon and chlorine compound specific isotope analysis (CSIA) of bis(2-chloroethyl) ether (BCEE) was performed to distinguish the primary processes contributing to observed concentration reductions in an anaerobic groundwater plume. Laboratory microcosms were constructed to demonstrate and obtain isotopic enrichment factors and dual-element CSIA trends from two potential transformation processes (1) anaerobic biodegradation using saturated sediment samples from the field site (ε=-14.8 and ε=-5.

Design, Synthesis, and Biological Activity of 1,2,3-Triazolobenzodiazepine BET Bromodomain Inhibitors.

A number of diazepines are known to inhibit bromo- and extra-terminal domain (BET) proteins. Their BET inhibitory activity derives from the fusion of an acetyl-lysine mimetic heterocycle onto the diazepine framework. Herein we describe a straightforward, modular synthesis of novel 1,2,3-triazolobenzodiazepines and show that the 1,2,3-triazole acts as an effective acetyl-lysine mimetic heterocycle.

Methods for Scarless, Selection-Free Generation of Human Cells and Allele-Specific Functional Analysis of Disease-Associated SNPs and Variants of Uncertain Significance.

With the continued emergence of risk loci from Genome-Wide Association studies and variants of uncertain significance identified from patient sequencing, better methods are required to translate these human genetic findings into improvements in public health. Here we combine CRISPR/Cas9 gene editing with an innovative high-throughput genotyping pipeline utilizing KASP (Kompetitive Allele-Specific PCR) genotyping technology to create scarless isogenic cell models of cancer variants in ~1 month. We successfully modeled two novel variants previously identified by our lab in the PALB2 gene in HEK239 cells, resulting in isogenic cells representing all three genotypes for both variants.