Cooperativity between Cas9 and hyperactive AID establishes broad and diversifying mutational footprints in base editors.

The partnership of DNA deaminase enzymes with CRISPR-Cas nucleases is now a well-established method to enable targeted genomic base editing. However, an understanding of how Cas9 and DNA deaminases collaborate to shape base editor (BE) outcomes has been lacking. Here, we support a novel mechanistic model of base editing by deriving a range of hyperactive activation-induced deaminase (AID) base editors (hBEs) and exploiting their characteristic diversifying activity.

CRISPR tiling screen reveals cancer epigenetic 'Goldilocks' state.

CRISPR tiling screens offer an efficient way to identify gain-of-function mutations in targets of cancer therapy. Recently, by utilizing these screens, Kwok et al. unexpectedly discovered mutations conferring drug addiction in lymphoma, revealing a requirement for a 'just right' window of histone methylation crucial for cancer survival.

Structure-Guided Design of a Potent and Specific Inhibitor against the Genomic Mutator APOBEC3A.

Nucleic acid structure plays a critical role in governing the selectivity of DNA- and RNA-modifying enzymes. In the case of the APOBEC3 family of cytidine deaminases, these enzymes catalyze the conversion of cytosine (C) to uracil (U) in single-stranded DNA, primarily in the context of innate immunity. DNA deamination can also have pathological consequences, accelerating the evolution of viral genomes or, when the host genome is targeted by either APOBEC3A (A3A) or APOBEC3B (A3B), promoting tumor evolution leading to worse patient prognosis and chemotherapeutic resistance.

The Base-Editing Enzyme APOBEC3A Catalyzes Cytosine Deamination in RNA with Low Proficiency and High Selectivity.

Human APOBEC3A (A3A) is a nucleic acid-modifying enzyme that belongs to the cytidine deaminase family. Canonically, A3A catalyzes the deamination of cytosine into uracil in single-stranded DNA, an activity that makes A3A both a critical antiviral defense factor and a useful tool for targeted genome editing. However, mutagenesis by A3A has also been readily detected in both cellular DNA and RNA, activities that have been implicated in cancer.

Controllable genome editing with split-engineered base editors.

DNA deaminase enzymes play key roles in immunity and have recently been harnessed for their biotechnological applications. In base editors (BEs), the combination of DNA deaminase mutator activity with CRISPR-Cas localization confers the powerful ability to directly convert one target DNA base into another. While efforts have been made to improve targeting efficiency and precision, all BEs so far use a constitutively active DNA deaminase.

A unilateral inguinofemoral granulomatous lymphadenitis in a two-year-old girl. A case report.

is an environmental contaminant and is considered as an emerging human pathogen. We report the case of a granulomatous lymphadenitis in a two-year-old girl. A two-year-old, previously healthy, Caucasian girl developed a unilateral inguinofemoral granulomatous lymphadenitis with .

Ultra-Wideband and Wide-Angle Microwave Metamaterial Absorber.

In order to extend the performance of radar absorbing materials, it is necessary to design new structures with wideband properties and large angles of incidence which are also as thin as possible. The objective of this work, realized within the framework of the SAFAS project (self-complementary surface with low signature) is, then, the development of an ultra-wideband microwave absorber of low thickness. The design of such material requires a multilayered structure composed with dielectric layers, metasurfaces, and wide-angle impedance matching layers.

Physicochemical characterization of colored soluble protein fractions extracted from Spirulina ( Spirulina platensis).

The aim of this study was to evaluate the physicochemical properties of Spirulina colored soluble protein fractions extracted from spray-dried Spirulina powder. Three fractions, including the blue soluble Spirulina protein, the green soluble Spirulina protein, and the total soluble Spirulina protein fractions were obtained. Investigations on their behavior at air/water interface were carried out using dynamic methods of drop volume and bubble pressure surface tension measurements.

Yield, Composition and Antioxidant Capacity of the Essential Oil of Sweet Basil and Holy Basil as Influenced by Distillation Methods.

The profile and bioactivity of essential oil (EO) depends on genetic, environmental, and other factors. We hypothesized that the basil EO may be influenced by the distillation methods. Hence, a study was conducted to evaluate the effect of steam distillation (SD) and hydrodistillation (HD) extraction method on the yield, composition, and bioactivity of EO of sweet basil (Ocimum basilicum) and holy basil (Ocimum tenuiflorum).

Coseismic and Postseismic Fault Slip for the 17 August 1999, M = 7.5, Izmit, Turkey Earthquake.

We use Global Positioning System (GPS) observations and elastic half-space models to estimate the distribution of coseismic and postseismic slip along the Izmit earthquake rupture. Our results indicate that large coseismic slip (reaching 5.7 meters) is confined to the upper 10 kilometers of the crust, correlates with structurally distinct fault segments, and is relatively low near the hypocenter.

Heightened odds of large earthquakes near istanbul: An interaction-based probability calculation.

We calculate the probability of strong shaking in Istanbul, an urban center of 10 million people, from the description of earthquakes on the North Anatolian fault system in the Marmara Sea during the past 500 years and test the resulting catalog against the frequency of damage in Istanbul during the preceding millennium. Departing from current practice, we include the time-dependent effect of stress transferred by the 1999 moment magnitude M = 7.4 Izmit earthquake to faults nearer to Istanbul.

Seismic hazard in the Marmara Sea region following the 17 August 1999 Izmit earthquake.

On 17 August 1999, a destructive magnitude 7.4 earthquake occurred 100 km east of Istanbul, near the city of Izmit, on the North Anatolian fault. This 1,600-km-long plate boundary slips at an average rate of 2-3 cm yr(-1), and historically has been the site of many devastating earthquakes.

Radioimmunoassay of cortisone in serum, urine, and saliva to assess the status of the cortisol-cortisone shuttle.

We have developed a new assay for cortisone (E) in serum, saliva, and urine involving Celite chromatography followed by RIA with 125I-labeled E and scintillation proximity assay. The chromatography step separates cortisol (F) from E, and in combination with their RIAs, permits assessment of the status of the F-E shuttle. We report the results of basal, postcorticotropin (ACTH), and postdexamethasone E and F concentrations and their circadian fluctuations in the serum, saliva, and urine of healthy volunteers.

[Pefloxacin as a first-line treatment for nephrotic syndrome in minimal glomerular lesions in the adult. Multicenter study of 32 patients].

Minimal change nephrotic syndrome (MCNS) is the most frequent single cause of nephrotic syndrome occurring both in adults and children. Although it appears to be a self-limiting disorder (10% spontaneous remissions within the fortnight following the initial flare), MCNS displays a high rate of complications during the nephrotic period (10 to 15% cases) and prompts one to treat patients as early as possible. Corticosteroids are currently used as first-line treatment.