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Human hyaluronidase 1 (HYAL1) and PH20 play vital roles in degrading hyaluronic acids through the substrate-assisted double displacement mechanism. While HYAL1, a lysosomal enzyme, functions optimally under acidic conditions, PH20, a sperm surface hyaluronidase, displays a broader pH range, from acidic to neutral. Our objective was to extend HYAL1's pH range towards neutral pH by introducing repulsive charge-charge interactions involving the catalytic Glu131, increasing its pKa as the proton donor. Substituting individual acidic residues in the β3-loop (S77D), β3'-β3″ hairpin (T86D and P87E), and at Ala132 (A132D and A132E) enabled HYAL1 to demonstrate enzyme activity at pH 7, with the mutants S77D, P87E, and A132E showing the highest activity in the substrate gel assay. However, double and triple substitutions, including S77D/T86D/A132E as found in the PH20 configuration, did not result in enhanced activity compared to single substitutions. Conversely, PH20 mutants with non-acidic substitutions, such as D94S in the β3-loop and D103T in the β3'-β3″ hairpin, significantly reduced activity within the pH range of 4 to 7. However, the PH20 mutant E149A, reciprocally substituted compared to A132E in HYAL1, exhibited activity similar to PH20 wild-type (WT) at pH 7. In a turbidimetric assay, HYAL1 mutants with single acidic substitutions exhibited activity similar to that of PH20 WT at pH 7. These results suggest that substituting acidic residues near Glu131 results in HYAL1 activity at neutral pH through electrostatic repulsion. This study highlights the significance of charge-charge interactions in both HYAL1 and PH20 in regulating the pH-dependent activity of hyaluronidases.

AbstractWe introduce dGSLM, the first “textless” model able to generate audio samples of naturalistic spoken dialogues. It uses recent work on unsupervised spoken unit discovery coupled with a dual-tower transformer architecture with cross-attention trained on 2000 hours of two-channel raw conversational audio (Fisher dataset) without any text or labels. We show that our model is able to generate speech, laughter, and other paralinguistic signals in the two channels simultaneously and reproduces more naturalistic and fluid turn taking compared to a text-based cascaded model.1,2

In this study, ZnO/g-C3N4 nanocomposites were prepared via a physical mixing-calcination process for improved degradation of dyes under visible light irradiation. The BET surface area, pore volume, crystal size, and pHpzc of the ZnO/g-C3N4 composite were 3.9 m2/g, 0.034 cm3/g, 18.1 nm, and 7.7, respectively. Although the morphology of the ZnO/g-C3N4 composite was very different from that of pure g-C3N4, their average pore sizes were similar. The Eg of the ZnO/g-C3N4 composite (3.195 eV) was slightly lower than that of ZnO (3.195) but much higher than that of g-C3N4 (2.875). The interface interaction of ZnO and g-C3N4, which was revealed by oscillations of Zn-C, benefited the transport of photoinduced charge carriers and reduced the recombination of electron-hole. As the result, the ZnO/g-C3N4 composite had higher photocatalytic activity than ZnO and g-C3N4. Its degradation efficiency (DE) value for methylene blue (MB) in 90 min and rate constant were 93.2 % and 0.025 min‑1, respectively. In addition, the effects of ZnO/urea molar ratio, catalyst dosage, solution pH, and concentration of dye on photocatalytic degradation of MB were completely investigated. The photocatalytic performance of the ZnO/g-C3N4 composite was evaluated by the degradation of other persistent organic compounds, also compared to other catalysts in the literatures. Copyright © 2022 by Authors, Published by BCREC Group. This is an open access article under the CC BY-SA License (https://creativecommons.org/licenses/by-sa/4.0).

The Spitzenkörper (SPK) is a polarized accumulation of proteins and secretory vesicles associated with tip growth of fungal hyphae. Here, Zheng et al. study SPK assembly and dynamics, identify SPK protein scaffolds and associated proteins, and reveal similarities with other scaffolds from metazoans.

The fungal Ascomycota provide a model phylum to investigate the evolution of complex multicellularity. Here, the authors combine genome sequencing with comparative and functional genomics to identify diverse endomembrane related machineries associated with the gain and loss of fungal complexity.

Horizontal gene transfer (HGT) can promote evolutionary adaptation by transforming a species' relationship to the environment. In most well-understood cases of HGT, acquired and donor functions appear to remain closely related. Thus, the degree to which HGT can lead to evolutionary novelties remains unclear. Mucorales fungi sense gravity through the sedimentation of vacuolar protein crystals. Here, we identify the octahedral crystal matrix protein (OCTIN). Phylogenetic analysis strongly supports acquisition of octin by HGT from bacteria. A bacterial OCTIN forms high-order periplasmic oligomers, and inter-molecular disulphide bonds are formed by both fungal and bacterial OCTINs, suggesting that they share elements of a conserved assembly mechanism. However, estimated sedimentation velocities preclude a gravity-sensing function for the bacterial structures. Together, our data suggest that HGT from bacteria into the Mucorales allowed a dramatic increase in assembly scale and emergence of the gravity-sensing function. We conclude that HGT can lead to evolutionary novelties that emerge depending on the physiological and cellular context of protein assembly.

Restructuring in Vietnam has become a critical necessity to ensure efficiency and stability, especially in the context of long-lasting recession in the economy as a whole. This paper reviews Vietnam’s economic growth model to point out the demand for restructuring the key blocks of the economy. The paper also discusses the road map for Vietnam’s restructuring process and synthesizes the initial achievements of the process so far.

Nowadays, the implementation and application of the BIM process in construction project management is a pressing need. This aligns with the global development trends in the construction sector and project information management in general. Numerous scholars and companies are actively engaged in learning, understanding, and investigating various aspects of BIM to stay up-to-date and meet the inevitable developmental requirements. This study focuses on the role and application of BIM, intending to identify limitations that hinder its fulfillment of expectations in project schedule management. In addition, it explores studies that show how other countries have effectively employed BIM in project management and progress tracking throughout the project lifecycle. The study aims to address three main objectives: (a) comprehensively examine and provide evidence related to the concept of BIM in project schedule management, (b) present the benefits of applying BIM in comparison to traditional methods in project management and operation, and (c) identify limitations stemming from various factors that may pose challenges in the application of BIM in project schedule management. [ABSTRACT FROM AUTHOR]