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  • Article
    Wang Z, Yang R, Lv W, Zhang W, Meng X, Liu W.
    Microbiol Spectr. 2022 08 31;10(4):e0087222.
    The expression of cellulase genes in lignocellulose-degrading fungus Trichoderma reesei is induced by insoluble cellulose and its soluble derivatives. Membrane-localized transporter/transceptor proteins have been thought to be involved in nutrient uptake and/or sensing to initiate the subsequent signal transduction during cellulase gene induction. Crt1 is a sugar transporter proven to be essential for cellulase gene induction although the detailed mechanism of Crt1-triggered cellulase induction remains elusive. In this study, we focused on the C-terminus region of Crt1 which is predicted to exist as an unstructured cytoplasmic tail in T. reesei. Serial C-terminal truncation of Crt1 revealed that deleting the last half of the C-terminal region of Crt1 hardly affected its transporting activity or ability to mediate the induction of cellulase gene expression. In contrast, removal of the entire C-terminus region eliminated both activities. Of note, Crt1-C5, retaining only the first five amino acids of C-terminus, was found to be capable of transporting lactose but failed to restore cellulase gene induction in the Δcrt1 strain. Analysis of the cellular localization of Crt1 showed that Crt1 existed both at the plasma membrane and at the periphery of the nucleus although the functional relevance is not clear at present. Finally, we showed that the cellulase production defect of Δcrt1 was corrected by overexpressing Xyr1, indicating that Xyr1 is a potential regulatory target of the signaling cascade initiated from Crt1. IMPORTANCE The lignocellulose-degrading fungus T. reesei has been widely used in industrial cellulases production. Understanding the precise cellulase gene regulatory network is critical for its genetic engineering to enhance the mass production of cellulases. As the key membrane protein involved in cellulase expression in T. reesei, the detailed mechanism of Crt1 in mediating cellulase induction remains to be investigated. In this study, the C-terminal region of Crt1 was found to be vital for its transport and signaling receptor functions. These two functions are, however, separable because a C-terminal truncation mutant is capable of sugar transporting but loses the ability to mediate cellulase gene expression. Furthermore, the key transcriptional activator Xyr1 represents a downstream target of the Crt1-initiated signaling cascade. Together, our research provides new insights into the function of Crt1 and further contributes to the unveiling of the intricate signal transduction process leading to efficient cellulase gene expression in T. reesei.
    Digital Access Access Options
  • Article
    Lista MJ, Ficarelli M, Wilson H, Kmiec D, Youle RL, Wanford J, Winstone H, Odendall C, Taylor IA, Neil SJD, Swanson CM.
    J Virol. 2023 01 31;97(1):e0087222.
    The zinc finger antiviral protein (ZAP) inhibits viral replication by directly binding CpG dinucleotides in cytoplasmic viral RNA to inhibit protein synthesis and target the RNA for degradation. ZAP evolved in tetrapods and there are clear orthologs in reptiles, birds, and mammals. When ZAP emerged, other proteins may have evolved to become cofactors for its antiviral activity. KHNYN is a putative endoribonuclease that is required for ZAP to restrict retroviruses. To determine its evolutionary path after ZAP emerged, we compared KHNYN orthologs in mammals and reptiles to those in fish, which do not encode ZAP. This identified residues in KHNYN that are highly conserved in species that encode ZAP, including several in the CUBAN domain. The CUBAN domain interacts with NEDD8 and Cullin-RING E3 ubiquitin ligases. Deletion of the CUBAN domain decreased KHNYN antiviral activity, increased protein expression and increased nuclear localization. However, mutation of residues required for the CUBAN domain-NEDD8 interaction increased KHNYN abundance but did not affect its antiviral activity or cytoplasmic localization, indicating that Cullin-mediated degradation may control its homeostasis and regulation of protein turnover is separable from its antiviral activity. By contrast, the C-terminal residues in the CUBAN domain form a CRM1-dependent nuclear export signal (NES) that is required for its antiviral activity. Deletion or mutation of the NES increased KHNYN nuclear localization and decreased its interaction with ZAP. The final 2 positions of this NES are not present in fish KHNYN orthologs and we hypothesize their evolution allowed KHNYN to act as a ZAP cofactor. IMPORTANCE The interferon system is part of the innate immune response that inhibits viruses and other pathogens. This system emerged approximately 500 million years ago in early vertebrates. Since then, some genes have evolved to become antiviral interferon-stimulated genes (ISGs) while others evolved so their encoded protein could interact with proteins encoded by ISGs and contribute to their activity. However, this remains poorly characterized. ZAP is an ISG that arose during tetrapod evolution and inhibits viral replication. Because KHNYN interacts with ZAP and is required for its antiviral activity against retroviruses, we conducted an evolutionary analysis to determine how specific amino acids in KHNYN evolved after ZAP emerged. This identified a nuclear export signal that evolved in tetrapods and is required for KHNYN to traffic in the cell and interact with ZAP. Overall, specific residues in KHNYN evolved to allow it to act as a cofactor for ZAP antiviral activity.
    Digital Access Access Options
  • Article
    Castro IRR, Farias DR, Berti TL, Andrade PG, Anjos LAD, Alves-Santos NH, Lacerda EMA, Freitas MB, Kac G, Brazilian Consortium on Child Nutrition.
    Cad Saude Publica. 2023;39(Suppl 2):e00087222.
    This study compared the distribution of stunting and height-for-age (HAZ) Z-scores among age groups in data from the Brazilian National Survey on Demography and Health of Women and Children (PNDS 2006) and the Brazilian National Survey on Child Nutrition (ENANI-2019). The final sample comprised 4,408 and 14,553 children < 59 months of age in the PNDS 2006 and ENANI-2019, respectively. Children with HAZ scores < -2 according to the World Health Organization (WHO) growth standard were classified as stunted. Prevalence, 95% confidence intervals (95%CI), means, and standard deviations were estimated for Brazil and according to age. The distribution of HAZ scores at each age (in months) was estimated using the svysmooth function of the R survey package. Analyses considered the complex sampling design of the studies. Statistical differences were determined by analyzing the 95%CI of the overlap of point estimates. From 2006 to 2019, the prevalence of stunting for children < 12 months of age increased from 4.7% to 9%. As expected, the smoothed curves showed a higher mean HAZ score for children < 24 months of age in 2006 than in 2019 with no overlap of 95%CI among children aged 6-12 months. For children ≥ 24 months of age, we observed a higher mean HAZ score in 2019. Although the prevalence of stunting among children < 59 months of age was similar between 2006 and 2019, mean HAZ scores among children ≥ 24 months of age increased, whereas the mean HAZ score among children < 24 months of age decreased. Considering the deterioration in living conditions and the potential impact of the COVID-19 pandemic, we expect a greater prevalence of stunting in Brazil in the near future.
    Digital Access Access Options
  • Article
    Hu Z, Zhou J, Li Z, Xiang J, Qian Z, Wu J, Zhang M, Zheng S.
    PLoS One. 2014;9(1):e87222.
    BACKGROUND: Salvage liver transplantation (SLT) has recently been proposed for recurrent hepatocellular carcinoma after liver resection; however, criteria for candidate assessment in SLT have not been thoroughly evaluated.
    METHODS AND FINDINGS: We retrospectively analyzed outcomes and factors affecting survival of 53 recipients who received SLT in the Liver Transplantation Center, The First Affiliated Hospital of Zhejiang University between 2004 and 2012. Thirty recipients fulfilled the Hangzhou criteria, of which 16 also fulfilled the Milan criteria, while the remaining 23 exceeded both criteria. The 1-year, 3-year and 5-year overall survival rates and tumor-free survival rates were both superior in patients fulfilling Milan or Hangzhou criteria compared with those exceeding the criteria. For recipients outside Milan criteria but within Hangzhou criteria, the 1-year, 3-year overall survival rates were 70.1%, 70.1%, similar to recipients within Milan criteria, with the 1-year, 3-year and 5-year overall survival of 93.8%%, 62.1% and 62.1% (P = 0.586). The tumor-free survival rates were also similar between these two subgroups, with 51.9% and 51.9% vs. 85.6%, 85.6% and 64.2% during the same time interval, respectively (P = 0.054). Cox regression analysis identified Hangzhou criteria (within vs. outside, hazard ratio (HR) 0.376) and diameter of the largest tumor (HR 3.523) to be independent predictors for overall survival. The only predictor for tumor-free survival was diameter of the largest tumor (HR 22.289).
    CONCLUSIONS: Hangzhou criteria safely expanded the candidate pool and are feasible in assessment of candidates for SLT. This is helpful in donor liver allocation in transplant practice.
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  • Book
    edited by Hooman Keshavarzi, Fahad Khan, Bilal Ali, Rania Awaad.
    Summary: "This text outlines for the first time a structured articulation of an emerging Islamic orientation to psychotherapy, a framework presented and known as Traditional Islamically Integrated Psychotherapy (TIIP). TIIP is an integrative model of mental health care that is grounded in the core principles of Islam while drawing upon empirical truths in psychology. The book introduces the basic foundations of TIIP, then delves into the writings of early Islamic scholars to provide a richer understanding of the Islamic intellectual heritage as it pertains to human psychology and mental health. Beyond theory, the book provides readers with practical interventional skills illustrated with case studies as well as techniques drawn inherently from the Islamic tradition. A methodology of case formulation is provided that allows for effective treatment planning and translation into therapeutic application. Throughout its chapters, the book situates TIIP within an Islamic epistemological and ontological framework, providing a discussion of the nature and composition of the human psyche, its drives, health, pathology, mechanisms of psychological change, and principles of healing. Mental health practitioners who treat Muslim patients, Muslim clinicians, students of the behavioral sciences and related disciplines, and anyone with an interest in spiritually oriented psychotherapies will greatly benefit from this illustrative and practical text"-- Provided by publisher.
    Digital Access TandFonline 2020