A Systematic Review and Meta-Analysis of Vocabulary Interventions for Deaf/Hard of Hearing Children and Adolescents.

PURPOSE: The development of vocabulary size in deaf/hard of hearing (DHH) children and adolescents can be delayed compared to their peers due to lack of access to early language input. Complementary vocabulary interventions are reported in the literature. Our aim is to evaluate the effectiveness of intervention methods for their vocabulary improvement. METHOD: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched five databases for peer-reviewed journal articles in English, published between 2000 and 2022 (inclusive), reporting vocabulary interventions for 2- to 18-year-old DHH children and adolescents without comorbidities. We conducted separate meta-analyses using a random-effects model on receptive oral vocabulary, expressive oral vocabulary, and signed vocabulary. We assessed the methodological quality of each paper. This review is preregistered in PROSPERO (International Prospective Register of Systematic Reviews) with ID CRD42021243479. RESULTS: We included 25 group studies in this review out of 1,724 identified records. The quality assessment of the studies revealed risk of bias ranging from some concerns to high risk. Experimental vocabulary instruction produced improvement in receptive oral vocabulary (Hedges's g = 1.08, 95% CI [0.25, 1.90], I2 = 93.46, p = .01), expressive oral vocabulary (Hedges's g = 1.00, 95% CI [0.18, 1.83], I2 = 96.37, p = .02), and signed vocabulary (Hedges's g = 1.88, 95% CI [1.09, 2.66], I2 = 96.01, p < .001) in the experimental groups. Written vocabulary and general vocabulary skills are also reported as a synthesis of results. CONCLUSIONS: Multisensory and multimodal explicit vocabulary instruction for DHH children and adolescents is helpful in improving vocabulary acquisition with respect to baseline levels. However, its effectiveness must be carefully interpreted due to the lack of proper control groups and details on treatment as usual reported in the studies. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.23646357.

Carrier Protein-Free Enzymatic Biaryl Coupling in Arylomycin A2 Assembly and Structure of the Cytochrome P450 AryC.

Invited for the cover of this issue are Sabine Schneider, Tobias A. M. Gulder and co-workers at Technical University of Dresden, Technical University of Munich and Ludwig-Maximillians-University Munich. The image depicts the crystal structure of the cytochrome P450 AryC from arylomycin biosynthesis. Read the full text of the article at 10.1002/chem.202103389.

Carrier Protein-Free Enzymatic Biaryl Coupling in Arylomycin A2 Assembly and Structure of the Cytochrome P450 AryC.

The arylomycin antibiotics are potent inhibitors of bacterial type I signal peptidase. These lipohexapeptides contain a biaryl structural motif reminiscent of glycopeptide antibiotics. We herein describe the functional and structural evaluation of AryC, the cytochrome P450 performing biaryl coupling in biosynthetic arylomycin assembly. Unlike its enzymatic counterparts in glycopeptide biosynthesis, AryC converts free substrates without the requirement of any protein interaction partner, likely enabled by a strongly hydrophobic cavity at the surface of AryC pointing to the substrate tunnel. This activity enables chemo-enzymatic assembly of arylomycin A2 that combines the advantages of liquid- and solid-phase peptide synthesis with late-stage enzymatic cross-coupling. The reactivity of AryC is unprecedented in cytochrome P450-mediated biaryl construction in non-ribosomal peptides, in which peptidyl carrier protein (PCP)-tethering so far was shown crucial both in vivo and in vitro.

Bypassing Biocatalytic Substrate Limitations in Oxidative Dearomatization Reactions by Transient Substrate Mimicking.

Enzymatic oxidative dearomatization is an efficient way to generate chiral molecules from simple arenes. One example is the flavin-dependent monooxygenase SorbC involved in sorbicillinoid biosynthesis. However, SorbC requires a long-chain keto substituent at its phenolic substrate, thus preventing its application beyond the synthesis of natural sorbicillinoids or close structural analogues. This work describes an approach to broaden the accessible product spectrum of SorbC by employing an ester functionality mimicking the natural substrate structure during enzymatic oxidation.

Expanding the Structural Space of Ribosomal Peptides: Autocatalytic N-Methylation in Omphalotin Biosynthesis.

Tail-Me: The N-methylation of backbone amide bonds in peptide natural products was thought to be exclusive to non-ribosomal peptides. A newly discovered methylation mechanism now brings this structural feature into the world of ribosomal peptides, thereby significantly expanding the structural diversity of ribosomally synthesized and post-translationally modified peptides (RiPPs).

Asperentin B, a New Inhibitor of the Protein Tyrosine Phosphatase 1B.

In the frame of studies on secondary metabolites produced by fungi from deep-sea environments we have investigated inhibitors of enzymes playing key roles in signaling cascades of biochemical pathways relevant for the treatment of diseases. Here we report on a new inhibitor of the human protein tyrosine phosphatase 1B (PTP1B), a target in the signaling pathway of insulin. A new asperentin analog is produced by an Aspergillussydowii strain isolated from the sediment of the deep Mediterranean Sea. Asperentin B (1) contains an additional phenolic hydroxy function at C-6 and exhibits an IC50 value against PTP1B of 2 µM in vitro, which is six times stronger than the positive control, suramin. Interestingly, asperentin (2) did not show any inhibition of this enzymatic activity. Asperentin B (1) is discussed as possible therapeutic agents for type 2 diabetes and sleeping sickness.

Structure of a putative fluorinated natural product from Streptomyces sp. TC1.

Fluorine-containing natural products are extremely rare. The recent report on the isolation and biological activity of the bacterial secondary metabolite 3-(3,5-di-tert-butyl-4-fluorophenyl)propionic acid was thus highly remarkable. The compound contained the first aromatic fluorine substituent known to date in any natural product. The promise to discover an enzyme capable of aromatic fluorination in the producing strain Streptomyces sp. TC1 prompted our immediate interest. A close inspection of the originally reported analytical data of the fluoro metabolite revealed inconsistencies that triggered us to validate the reported structure. The results of these efforts are presented in this communication.

The biocatalytic repertoire of natural biaryl formation.

The catalytic and selective construction of carbon-carbon bonds for the generation of complex molecules is one of the most important tasks in organic chemistry. This was clearly highlighted by the 2010 Nobel Prize in Chemistry, which was awarded for the development of Pd-catalyzed cross-coupling reactions. The underlying concept of cross-linking building blocks to generate molecular complexity can also be widely found in natural product biosynthesis. Impressive examples for such natural cross-coupling reactions are biosynthetic processes for the assembly of biaryl moieties in natural products--highly efficient enzymatic reactions that often achieve synthetically yet unmatched selectivities. This Minireview highlights selected examples that showcase these fascinating biotransformations.