Relative flux trade-offs and optimization of metabolic network functionalities

Trade-offs between traits are present across different levels of biological systems and ultimately reflect constraints imposed by physicochemical laws and the structure of underlying biochemical networks. Yet, mechanistic explanation of how trade-offs between molecular traits arise and how they relate to optimization of fitness-related traits remains elusive. Here, we introduce the concept of relative flux trade-offs and propose a constraint-based approach, termed FluTOr, to identify metabolic reactions whose fluxes are in relative trade-off with respect to an optimized fitness-related cellular task, like growth. We then employed FluTOr to identify relative flux trade-offs in the genome-scale metabolic networks of Escherichia coli, Saccharomyces cerevisiae, and Arabidopsis thaliana. For the metabolic models of E. coli and S. cerevisiae we showed that: (i) the identified relative flux trade-offs depend on the carbon source used and that (ii) reactions that participated in relative trade-offs in both species were implicated in cofactor biosynthesis. In contrast to the two microorganisms, the relative flux trade-offs for the metabolic model of A. thaliana did not depend on the available nitrogen sources, reflecting the differences in the underlying metabolic network as well as the considered environments. Lastly, the established connection between relative flux trade-offs allowed us to identify overexpression targets that can be used to optimize fitness-related traits. Altogether, our computational approach and findings demonstrate how relative flux trade-offs can shape optimization of metabolic tasks, important in biotechnological applications. (c) 2022 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.Peer reviewe

Acute bone response to whole body vibration in healthy pre-pubertal boys

The skeleton responds to mechanical stimulation. We wished to ascertain the magnitude and speed of the growing skeleton’s response to a standardised form of mechanical stimulation, vibration. 36 prepubertal boys stood for 10 minutes in total on one of two vibrating platforms (high (>2 g) or low (<1 g) magnitude vibration) on either 1, 3 or 5 successive days (n=12 for each duration); 15 control subjects stood on an inactive platform. Blood samples were taken at intervals before and after vibration to measure bone formation (P1NP, osteocalcin) and resorption (CTx) markers as well as osteoprotegerin and sclerostin. There were no significant differences between platform and control groups in bone turnover markers immediately after vibration on days 1, 3 and 5. Combining platform groups, at day 8 P1NP increased by 25.1% (CI 12.3 to 38.0; paired t-test p=0.005) and bone resorption increased by 10.9% (CI 3.6 to 18.2; paired t-test p=0.009) compared to baseline. Osteocalcin, osteoprotogerin and sclerostin did not change significantly. The growing skeleton can respond quickly to vibration of either high or low magnitude. Further work is needed to determine the utility of such “stimulation-testing” in clinical practice

The role of the intensive care unit environment and health-care workers in the transmission of bacteria associated with hospital acquired infections

The goal of this study was to attempt to determine the rate of contamination of health-care workers' (HCWs) hands and environmental surfaces in intensive care units (ICU) by the main bacteria associated with hospital acquired infections (HAIs) in Tehran, Iran. A total of 605 and 762 swab samples were obtained from six ICU environments and HCWs' hands. Identification of the bacterial isolates was performed according to standard biochemical methods, and their antimicrobial susceptibility was determined based on the guidelines recommended by clinical and laboratory standards institute (CLSI). The homology of the resistance patterns was assessed by the NTSYSsp software. The most frequent bacteria on the HCWs' hands and in the environmental samples were Acinetobacter baumannii (1.4 and 16.5, respectively), Staphylococcus aureus (5.9 and 8.1, respectively), S. epidermidis (20.9 and 18.7, respectively), and Enterococcus spp. (1 and 1.3, respectively). Patients' oxygen masks, ventilators, and bed linens were the most contaminated sites. Nurses' aides and housekeepers were the most contaminated staff. Imipenem resistant A. baumannii (94 and 54.5), methicillin-resistant S. aureus (MRSAs, 59.6 and 67.3), and vancomycin resistant Enterococci (VREs, 0 and 25) were detected on the hands of ICU staff and the environmental samples, respectively. Different isolates of S. aureus and Enterococcus spp. showed significant homology in these samples. These results showed contamination of the ICU environments and HCWs with important bacterial pathogens that are the main risk factors for HAIs in the studied hospitals. © 2015 King Saud Bin Abdulaziz University for Health Sciences

Nanopore native RNA sequencing of a human poly(A) transcriptome

High-throughput complementary DNA sequencing technologies have advanced our understanding of transcriptome complexity and regulation. However, these methods lose information contained in biological RNA because the copied reads are often short and modifications are not retained. We address these limitations using a native poly(A) RNA sequencing strategy developed by Oxford Nanopore Technologies. Our study generated 9.9 million aligned sequence reads for the human cell line GM12878, using thirty MinION flow cells at six institutions. These native RNA reads had a median length of 771 bases, and a maximum aligned length of over 21,000 bases. Mitochondrial poly(A) reads provided an internal measure of read-length quality. We combined these long nanopore reads with higher accuracy short-reads and annotated GM12878 promoter regions to identify 33,984 plausible RNA isoforms. We describe strategies for assessing 3′ poly(A) tail length, base modifications and transcript haplotypes

YASS: Yet Another Spike Sorter

submittedVersio

Assessing the Validity and Reliability of the Farsi Version of Inventory Drug-Taking Situations

Objective:Inventory Drug-Taking Situations (IDTS) is a universal instrument used to determine high-risk situations resulting in drug abuse. The aim of this study was to translate this questionnaire to Farsi, and to assess its validity and reliability by applying it to Iranian drug users.Methods:As a psychometric study, 300 drug users participated in a treatment program in National Center of Addiction Studies filled in a version of Inventory of Drug Taking Situations. We assessed face and content validity, internal consistency, and reliability based on the completed questionnaires, using test-retest method and confirmatory factor analysis.Results:Internal consistency analysis confirmed that all subscales of IDTS were reliable (Cronbach alpha was ranging from 0.7 to 0.81). Analyses indicated that each of the subscales was unifactorial; however, unpleasant emotions had a second eigenvalue that was nearly large enough to be a second factor. Confirmatory factor analysis was used to test the fit of the data to the original version of IDTS. Based on goodness of fit indices, we found that all factors were fitted (χ2/df=1.43, GFI=0.98, RMSEA=0.038). The test-retest reliability was satisfactory(r>0.6).Conclusion:The Farsi version of Inventory of Drug Taking Situations was shown to be a valid and reliable instrument to apply in clinical and research settings in Iran