Conformational switching of Arp5 subunit regulates INO80 chromatin remodeling.

The INO80 chromatin remodeler is a versatile enzyme capable of several functions, including spacing nucleosomes equal distances apart, precise positioning of nucleosomes based on DNA shape/sequence and exchanging histone dimers. Within INO80, the Arp5 subunit plays a central role in INO80 remodeling, evidenced by its interactions with the histone octamer, nucleosomal and extranucleosomal DNA, and its necessity in linking INO80's ATPase activity to nucleosome movement. We find two distinct regions of Arp5 binding near the acidic pocket of nucleosomes.

Cas9/Nickase-induced allelic conversion by homologous chromosome-templated repair in somatic cells.

Repair of double-strand breaks (DSBs) in somatic cells is primarily accomplished by error-prone nonhomologous end joining and less frequently by precise homology-directed repair preferentially using the sister chromatid as a template. Here, a system performs efficient somatic repair of both DSBs and single-strand breaks (SSBs) using intact sequences from the homologous chromosome in a process we refer to as homologous chromosome-templated repair (HTR). Unexpectedly, HTR-mediated allelic conversion at the locus was more efficient (40 to 65%) in response to SSBs induced by Cas9-derived nickases D10A or H840A than to DSBs induced by fully active Cas9 (20 to 30%).

A nickase Cas9 gene-drive system promotes super-Mendelian inheritance in Drosophila.

CRISPR-based gene-drives have been proposed for managing insect populations, including disease-transmitting mosquitoes, due to their ability to bias their inheritance toward super-Mendelian rates (>50%). Current technologies use a Cas9 that introduces DNA double-strand breaks into the opposing wild-type allele to replace it with a copy of the gene-drive allele via DNA homology-directed repair. However, the use of different Cas9 versions is unexplored, and alternative approaches could increase the available toolkit for gene-drive designs.

Oral immunotherapy in severe cow's milk allergic patients treated with omalizumab: Real life survey from a Spanish registry.

Background: Oral immunotherapy is a frequent treatment for the management of food allergies, but adverse events (AE) are common. This study assessed the outcome of cow's milk oral immunotherapy (MOIT) in severe cow`s milk-allergic patients treated with omalizumab in a real-life setting.

Methods: OmaBASE was a national, multicenter, open, and observational registry that collected clinical, immunologic, and treatment from patients with food allergy receiving omalizumab.

Active Genetic Neutralizing Elements for Halting or Deleting Gene Drives.

CRISPR-Cas9-based gene drive systems possess the inherent capacity to spread progressively throughout target populations. Here we describe two self-copying (or active) guide RNA-only genetic elements, called e-CHACRs and ERACRs. These elements use Cas9 produced in trans by a gene drive either to inactivate the cas9 transgene (e-CHACRs) or to delete and replace the gene drive (ERACRs).

Gal d 6 is the second allergen characterized from egg yolk.

Only one allergen from the egg yolk, alpha-livetin (Gal d 5) has been described thus far. A new egg yolk allergen was detected studying 27 egg allergic patients. The study was performed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and IgE-immunoblotting and IgE-immunoblotting-inhibition assays.

Selective allergy to lobster in a case of primary sensitization to house dust mites.

Allergy to only 1 kind of seafood is uncommon. We report a case of selective allergy to lobster. We studied a 30-year-old man who suffered generalized urticaria, facial erythema, and pharyngeal pruritus after eating lobster.

Lettuce-induced anaphylaxis. Identification of the allergen involved.

Background: Only 2 allergenic proteins have been described in lettuce allergy: a 16-kDa protein (putative profilin) and a lipid transfer protein (LTP) named Lac s 1.

Objective: Our aim was to identify the allergens involved in the anaphylactic reactions of 2 patients who had eaten lettuce.

Methods: The study was performed by Ig (immunoglobulin)-E immunodetection and immunodetection-inhibition assays.

Comparative cytotoxicity of C-1311 in colon cancer in vitro and in vivo using the hollow fiber assay.

The aim of this study was to investigate the antiproliferative effects of C-1311 (Symadex), a member of the imidazoacridinone family, in human colorectal cancer cells. In the in vitro screen, C-1311 led to the most prominent growth inhibition in HT29, HCT116, and COLO205 cell lines when compared to oxaliplatin, CPT-11, DFUR, 5-FU and capecitabine. The GI(50)values for C-1311 ranged from 0.

Sensitization to serum albumins in children allergic to cow's milk and epithelia.

Patients with persistent milk allergy and specific immunoglobulin E (IgE) to bovine serum albumin (BSA) have a greater risk of rhinoconjunctivitis and asthma because of animal dander. To prove the cross-reactivity between serum albumin (SA) of different mammals in milk, meat, and epithelia and determine if heat treatment of meats decrease the allergenicity of albumins. The study was performed using SDS-PAGE and IgE-immunoblotting using sera from eight patients sensitized to milk, BSA, and animal danders.

Comparative analysis of xanafide cytotoxicity in breast cancer cell lines.

Xanafide, a DNA-intercalating agent and topoisomerase II inhibitor, has previously demonstrated comparable cytotoxicity to the parent drug amonafide (NSC 308847). The current study was conducted to investigate further the anti-proliferative effects of xanafide in human breast cancer cell lines, in vitro and in vivo. The in vitro activity of xanafide against MCF-7, MDA-MB-231, SKBR-3 and T47D cell lines was compared to that of paclitaxel, docetaxel, gemcitabine, vinorelbine and doxorubicin.

Effect of poly-L-lysine coating on macrophage activation by alginate-based microcapsules: assessment using a new in vitro method.

The characteristics of the microcapsule surface, which interacts directly with the host macrophages, may have a role in the biocompatibility of alginate-poly-L-lysine (PLL)-alginate (APA) microcapsule. The objectives of the study were: 1) to develop and validate a simple, rapid, and sensitive in vitro method for assessing microcapsule biocompatibility, based on microcapsule coincubation with macrophages and measurement, by reverse transcriptase-polymerase chain reaction, of cytokine mRNA expression, and 2) to evaluate the effect of alginate purification and PLL coating on macrophage activation. The mRNA expression of tumor necrosis factor-alpha and interleukin-1beta was significantly higher when macrophages were coincubated with beads made with nonpurified compared with purified alginate (p<0.

Freezing protects against allergy to Anisakis simplex.

Background: Allergic reactions to Anisakis simplex have been described following ingestion of fish and were thought to be possible even if seafood is frozen or well-cooked.

Objective: This study aimed to confirm, by challenge test, that dead A. simplex larvae are not able to trigger allergic reactions in patients with proven hypersensitivity to this parasite.

Allergy to Anacardiaceae: description of cashew and pistachio nut allergens.

Some members of the Anacardiaceae family, such as cashew nut, pistachio nut and mango, have been reported to cause immediate allergic reactions. We report three cases of anaphylaxis to cashew nuts. With the aim of describing the allergens existing in cashew and pistachio nuts, patients were prick tested with cashew and pistachio extracts.