Edital

Kinetoplastid pathogens including Trypanosoma brucei , T. cruzi , and Leishmania species, are early diverged, eukaryotic, unicellular parasites. Functional understanding of many proteins from these pathogens has been hampered by limited sequence homology to proteins from other model organisms. Here we describe the development of a high-throughput deep mutational scanning approach in T. brucei that facilitates rapid and unbiased assessment of the impacts of many possible amino acid substitutions within a protein on cell fitness, as measured by relative cell growth...

STUDY QUESTION: Is the Tcte1 mutation causative for male infertility? SUMMARY ANSWER: Our collected data underline the complex and devastating effect of the single-gene mutation on the testicular molecular network, leading to male reproductive failure. WHAT IS KNOWN ALREADY: Recent data have revealed mutations in genes related to axonemal dynein arms as causative for morphology and motility abnormalities in spermatozoa of infertile males, including dysplasia of fibrous sheath (DFS) and multiple morphological abnormalities in the sperm flagella (MMAF)...

During organ regeneration, after the initial responses to injury, gene expression patterns similar to those in normal development are reestablished during subsequent morphogenesis phases. This supports the idea that regeneration recapitulates development and predicts the existence of genes that reboot the developmental program after the initial responses. However, such rebooting mechanisms are largely unknown. Here, we explore core rebooting factors that operate during Xenopus limb regeneration. Transcriptomic analysis of larval limb blastema reveals that hoxc12/c13 show the highest regeneration specificity in expression...

Reactivation of the fetal hemoglobin (HbF) in adult erythroid cells via genome editing is a strategy for the treatment of β-thalassemia and sickle cell disease. In related reports, the reactivation of HbF is regularly examined in erythroblasts which are generated from the adult CD34+ hematopoietic stem and progenitor cells (HSPCs). However, the procurement of adult HSPCs, either from the bone-marrow (BM) or from mobilized peripheral-blood (mPB), is difficult. Cord-blood (CB) is a readily available source of HSPCs...

The Onychostoma macrolepis have a unique survival strategy, overwintering in caves and returning to the river for reproduction in summer. The current knowledge on the developmental status of its testes during winter and summer is still undiscovered. We performed RNA-seq analysis on O. macrolepis testes between January and June, using the published genome (NCBI, ASM1243209v1). Through KEGG and GO enrichment analysis, we were able to identify 2111 differentially expressed genes (DEGs) and demonstrate their functions in signaling networks associated with the development of organism...

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RNA viruses, like SARS-CoV-2, depend on their RNA-dependent RNA polymerases (RdRp) for replication, which is error prone. Monitoring replication errors is crucial for understanding the virus's evolution. Current methods lack the precision to detect rare de novo RNA mutations, particularly in low-input samples such as those from patients. Here we introduce a targeted accurate RNA consensus sequencing method (tARC-seq) to accurately determine the mutation frequency and types in SARS-CoV-2, both in cell culture and clinical samples...

OBJECTIVE: Caffeine is widely used in preterm infants to prevent or treat apnoea of prematurity. Adverse gastrointestinal effects of caffeine have not been thoroughly researched in preterm infants. With this systematic review and meta-analysis, we aim to summarise the results of trials on the gastrointestinal effects of caffeine in preterm infants. DESIGN: We searched MEDLINE, Web of Science, Scopus and ClinicalTrials.gov up to 21 April 2023. We included randomised controlled trials assessing caffeine versus placebo in preterm neonates and reporting gastrointestinal side effects...

All cancer cells reprogram metabolism to support aberrant growth. Here, we report that cancer cells employ and depend on imbalanced and dynamic heme metabolic pathways, to accumulate heme intermediates, that is, porphyrins. We coined this essential metabolic rewiring "porphyrin overdrive" and determined that it is cancer-essential and cancer-specific. Among the major drivers are genes encoding mid-step enzymes governing the production of heme intermediates. CRISPR/Cas9 editing to engineer leukemia cell lines with impaired heme biosynthetic steps confirmed our whole-genome data analyses that porphyrin overdrive is linked to oncogenic states and cellular differentiation...

PURPOSE: Using a longitudinal design, this study aimed to describe inferential comprehension abilities of neglected French-speaking preschool children from 42 to 66 months of age in comparison to non-neglected peers, to examine the association with receptive vocabulary, and to determine whether rates of change in inferential abilities over time was stable between the two group conditions. METHOD: An inferential comprehension task and the French version of the Peabody Picture Vocabulary Test-Fourth Edition were administered to a group of neglected children ( n = 37-40) and to a group of same-age non-neglected children ( n = 71-91) at 42, 54, and 66 months old, as part of the Early Longitudinal Language and Neglect study...

A tool for precise, target-specific, efficient and affordable genome editing, it is a dream for many researchers, from those who do basic research to those who use it for applied research. Since 2012, we have the tool that almost fulfils such requirements; it is based on CRISPR/Cas systems. However, even CRISPR/Cas has limitations and obstacles that might surprise its users. In this review, we focus on the most frequently used variant, CRISPR/Cas9 from Streptococcus pyogenes, and highlight the key factors affecting its mutagenesis outcomes...

IMPORTANCE: Restrictions related to the COVID-19 pandemic disrupted the lives of young children, but the association between the pandemic and any changes in early childhood developmental milestone achievement in the US remains unclear. OBJECTIVES: To determine the association between the COVID-19 pandemic and changes in developmental screening scores among US children aged 0 to 5 years and to investigate whether caregivers self-reported more worries about their children or concerns about children's behavior during the pandemic, regardless of milestone achievement...

Chitooligosaccharides (COS) find numerous applications due to their exceptional properties. Enzymatic hydrolysis of chitosan by chitosanase is considered an advantageous route for COS production. Heterologous expression of chitosanase holds significant promise, yet studies using commonly employed Escherichia coli and Pichia pastoris strains encounter challenges in subsequent handling and industrial scalability. In this investigation, we opted for using the safe yeast strain Saccharomyces cerevisiae (GRAS), obviating the need for methanol induction, resulting in successful expression...

Because of its potent antioxidant effects, lycopene has been used in various industries including, but not limited to, food, medical, and cosmetic industries. Yarrowia lipolytica, a non-conventional yeast species, is a promising chassis due to its natural mevalonate (MVA) pathway, abundant precursor acetyl coenzyme A content, and oleaginous properties. Several gene editing tools have been developed for Y. lipolytica along with engineering strategies for tetraterpenoid production. In this study, we engineered Y...

High-performance electrical Joule heaters with high mechanical properties, low driving voltage, rapid response, and flexibility are highly desirable for portable thermal management. Herein, by using aligned bacterial cellulose (BC) and silver nanowire (AgNW), we fabricated a novel film heater based on Joule heating phenomena. The aligned BC film prepared by stretching BC hydrogel and hot-pressing drying technology showed outstanding mechanical properties and flexibility. The ultrahigh strength of up to 1018 MPa and the toughness of 20 MJ/m3 were obtained for the aligned BC film with 40% wet-stretching (BC-40)...

BACKGROUND: APC and MUTYH are both well-known colorectal polyposis causative genes. However, 30-50% of colorectal adenomatous polyposis cases are classified as colonic adenomatous polyposis of unknown etiology and lack identifiable pathogenic variants. Although guidelines recommend total proctocolectomy for colonic adenomatous polyposis of unknown etiology with over 100 adenomas, evidence is lacking. This study presents a unique case of localized colonic adenomatous polyposis of unknown etiology with multiple adenocarcinomas, treated with hemicolectomy and regional lymph node dissection...

Ansamycins, represented by the antituberculosis drug rifamycin, are an important family of natural products. To obtain new ansamycins, Streptomyces rapamycinicus IMET 43975 harboring an ansamycin biosynthetic gene cluster was fermented in a 50 L scale, and subsequent purification work led to the isolation of five known and four new analogues, where hygrocin W ( 2 ) belongs to benzoquinonoid ansamycins, and the other three hygrocins, hygrocins X-Z ( 6 - 8 ), are new seco-hygrocins. The structures of ansamycins ( 1 - 8 ) were determined by the analysis of spectroscopic (1D/2D NMR and ECD) and MS spectrometric data...

Reviews the book, Handbook of Positive Youth Development: Advancing Research, Policy, and Practice in Global Contexts edited by Radosveta Dimitrova and Nora Wiium (2021). This volume deals with both the applications and interventions of positive youth development (PYD) in the context of families and other systems in global contexts. Additionally, it advances empirical and theoretical knowledge in PYD, refinement of methodological issues, and measurement and integration of PYD-related knowledge with policy, research, and practice...

PRECIS: In recent years, ChatGPT has been widely used as a source of information. In our study, it was revealed that ChatGPT gives accurate information about glaucoma. PURPOSE: We examined the knowledge of ChatGPT about glaucoma. PATIENTS AND METHODS: Frequently asked questions about glaucoma found on websites of ophthalmology associations and hospitals, and social media applications were assessed. Evidence-Based Recommendations in the European Glaucoma Society Terminology and Guidelines for Glaucoma 5th Edition were evaluated...

The CRISPR-Cas9 technology has the potential to revolutionize the treatment of various diseases, including Rett syndrome, by enabling the correction of genes or mutations in human patient cells. However, several challenges need to be addressed before its widespread clinical application. These challenges include the low delivery efficiencies to target cells, the actual efficiency of the genome-editing process, and the precision with which the CRISPR-Cas system operates. Herein, the study presents a Magnetic Nanoparticle-Assisted Genome Editing (MAGE) platform, which significantly improves the transfection efficiency, biocompatibility, and genome-editing accuracy of CRISPR-Cas9 technology...