Liver-specific knockout of arginase-1 leads to a profound phenotype similar to inducible whole body arginase-1 deficiency

Arginase-1 (Arg1) converts arginine to urea and ornithine in the distal step of the urea cycle in liver. We previously generated a tamoxifen-inducible Arg1 deficient mouse model (Arg1-Cre) that disrupts Arg1 expression throughout the whole body and leads to lethality ≈ 2 weeks after gene disruption. Here, we evaluate if liver-selective Arg1 loss is sufficient to recapitulate the phenotype observed in global Arg1 knockout mice, as well as to gauge the effectiveness of gene delivery or hepatocyte transplantation to rescue the phenotype. Liver-selective Arg1 deletion was induced by using an adeno-associated viral (AAV)-thyroxine binding globulin (TBG) promoter-Cre recombinase vector administered to Arg1 "floxed" mice; Arg1(fl/fl) ). An AAV vector expressing an Arg1-enhanced green fluorescent protein (Arg1-eGFP) transgene was used for gene delivery, while intrasplenic injection of wild-type (WT) C57BL/6 hepatocytes after partial hepatectomy was used for cell delivery to "rescue" tamoxifen-treated Arg1-Cre mice. The results indicate that liver-selective loss of Arg1 (> 90% deficient) leads to a phenotype resembling the whole body knockout of Arg1 with lethality ≈ 3 weeks after Cre-induced gene disruption. Delivery of Arg1-eGFP AAV rescues more than half of Arg1 global knockout male mice (survival > 4 months) but a significant proportion still succumb to the enzyme deficiency even though liver expression and enzyme activity of the fusion protein reach levels observed in WT animals. Significant Arg1 enzyme activity from engrafted WT hepatocytes into knockout livers can be achieved but not sufficient for rescuing the lethal phenotype. This raises a conundrum relating to liver-specific expression of Arg1. On the one hand, loss of expression in this organ appears to be both necessary and sufficient to explain the lethal phenotype of the genetic disorder in mice. On the other hand, gene and cell-directed therapies suggest that rescue of extra-hepatic Arg1 expression may also be necessary for disease correction. Further studies are needed in order to illuminate the detailed mechanisms for pathogenesis of Arg1-deficiency

Factors Affecting Malaysian young consumers’ online purchase intention in social media websites

AbstractThe objective of this study was to examine factors that influence Malaysian young consumers’ online purchase intention through social media. The technology acceptance model and the theory of reasoned action were employed to develop the conceptual framework. Three factors, namely perceived ease of use, perceived usefulness and subjective norm were tested. Data were gathered from 297 undergraduate students using the stratified sampling method and multiple regression analysis were conducted to analyse the data. The results revealed that perceived usefulness was the most dominant factors that influence young consumers’ online purchase intention through social media, followed by perceived ease of use and subjective norm. The practical implications of this study were discussed

Bounds on the lightest Higgs boson mass with three and four fermion generations

We present lower bounds on the Higgs boson mass in the Standard Model with three and four fermion generations SM(3,4), as well as upper bounds on the lightest Higgs boson mass in the minimal supersymmetric extension of the SM with three and four generations MSSM(3,4). Our analysis utilizes the SM(3,4) renormalization-group-improved one-loop effective potential of the Higgs boson to find the upper bounds on the Higgs mass in the MSSM(3,4) while the lower bounds in the SM(3,4) are derived from considerations of vacuum stability. All the bounds increase as the degenerate fourth generation mass increases, providing more room in theory space that respects the increasing experimental lower limit of the Higgs mass.Comment: 24 pages, 10 figures, Some additional discussion added. Final version to be published in International Journal of Modern Physics

A Multilab Study of Bilingual Infants: Exploring the Preference for Infant-Directed Speech

From the earliest months of life, infants prefer listening to and learn better from infant-directed speech (IDS) compared with adult-directed speech (ADS). Yet IDS differs within communities, across languages, and across cultures, both in form and in prevalence. This large-scale, multisite study used the diversity of bilingual infant experiences to explore the impact of different types of linguistic experience on infants’ IDS preference. As part of the multilab ManyBabies 1 project, we compared preference for North American English (NAE) IDS in lab-matched samples of 333 bilingual and 384 monolingual infants tested in 17 labs in seven countries. The tested infants were in two age groups: 6 to 9 months and 12 to 15 months. We found that bilingual and monolingual infants both preferred IDS to ADS, and the two groups did not differ in terms of the overall magnitude of this preference. However, among bilingual infants who were acquiring NAE as a native language, greater exposure to NAE was associated with a stronger IDS preference. These findings extend the previous finding from ManyBabies 1 that monolinguals learning NAE as a native language showed a stronger IDS preference than infants unexposed to NAE. Together, our findings indicate that IDS preference likely makes similar contributions to monolingual and bilingual development, and that infants are exquisitely sensitive to the nature and frequency of different types of language input in their early environments

Tetra­kis(2,6-diamino­pyridinium) diphthalate 2,6-diamino­pyridine

In the title compound, 4C5H8N3 +·2C8H4O4 2−·C5H7N3, the asymmetric unit consists of two protonated diamino­pyridine cations, one phthalate anion and one half of a diamino­pyridine mol­ecule, which has twofold rotation symmetry and is disordered over two positions with a site-occupancy ratio of 0.534 (3):0.466 (3). In the disordered structure, both pyridine rings are essentially planar, with maximum deviations of 0.011 (2) and 0.006 (2) Å, and these two rings are inclined to one another at a dihedral angle of 79.86 (10)°. In the crystal structure, inter­molecular N—H⋯O and C—H⋯O hydrogen bonds link the ions and mol­ecules into a three-dimensional network. The structure is further stabilized by C—H⋯π inter­actions

Implications of Blockchain Deployment in Energy Supply Chain Management: Report Integrity

The recent strategic deployment of blockchain technology has demonstrated its capacity to provide a ledger platform that can be utilized to secure and effectively manage large scale of data. However, there is little effort to conceptualise the blockchain to facilitate energy supply chain management for report integrity. This study has conceptulized how blockchain technology can solve the challenges of energy supply chain management and energy reports' integrity. Critical review of past literature indicates that blockchain technology offers transparency of energy production and consumption reports. Blockchain keeps all the transactional records and guarantees security, and decentralization between the blockchain network. We have reviewed 121 relevant papers. Through the literature review, this study found blockchain is a suitable option for the integrity of energy reporting in energy supply chain management. It can be concluded that blockchain can help to alleviate the issues of transparency and cost related to energy reporting. This study recommends taking the lead to track energy use and participate in energy reporting using dependable technologies to increase company integrity and efficiency. Decision and policy makers should offer incentives and include regulations on energy reporting requirements

The third international hackathon for applying insights into large-scale genomic composition to use cases in a wide range of organisms

In October 2021, 59 scientists from 14 countries and 13 U.S. states collaborated virtually in the Third Annual Baylor College of Medicine & DNANexus Structural Variation hackathon. The goal of the hackathon was to advance research on structural variants (SVs) by prototyping and iterating on open-source software. This led to nine hackathon projects focused on diverse genomics research interests, including various SV discovery and genotyping methods, SV sequence reconstruction, and clinically relevant structural variation, including SARS-CoV-2 variants. Repositories for the projects that participated in the hackathon are available at https://github.com/collaborativebioinformatics

Selecting Total Quality Management (TQM) Best Practices in the Hotel Industry Environment : A Hybrid Model based on DEMATEL and ANP

Recently, developing strategies for sustainable development (SD) in the hotel industry has been seen globally as a crucial issue. Numerous management systems can assist the hotel industry in creating sustainable performance, such as Total Quality Management (TQM) which is well-reputed in the industry. As such, selecting TQM under an evolving hotel industry environment is seen as an important decision from a strategic perspective given it constitutes contradictory practices, thereby making it a multi-criteria decision-making (MCDM) issue. In achieving this aim, a Decision-Making Trial and Evaluation Laboratory (DEMATEL) approach was adopted in determining the inter-relationships between the primary practices and sub-practices in addition to applying the Analytic Network Process (ANP) for examining the weights of primary practices and sub-practices. In other words, this study aims to provide innovative insight to researchers and practitioners to examine the TQM optimal practices to be implemented incrementally in phases within the hotel industry environment