Genetic screens with barcoded PlasmoGEM vectors have identified thousands of Plasmodium berghei gene functions in haploid blood stages, gametocytes and liver stages. However, the formation of diploid cells by fertilisation has hindered similar research on the parasites' mosquito stages. In this study, we develop a scalable genetic system that uses barcoded gene targeting vectors equipped with a CRISPR-mediated homing mechanism to generate homozygous loss-of-function mutants after one parent introduces a modified allele into the zygote.
View Article and Find Full Text PDFThe elastic properties of nanoscale extracellular vesicles (EVs) are believed to influence their cellular interactions, thus having a profound implication in intercellular communication. However, accurate quantification of their elastic modulus is challenging due to their nanoscale dimensions and their fluid-like lipid bilayer. We show that the previous attempts to develop atomic force microscopy-based protocol are flawed as they lack theoretical underpinning as well as ignore important contributions arising from the surface adhesion forces and membrane fluctuations.
View Article and Find Full Text PDFAim: The occurrence of setup errors in external beam radiation is an inevitable aspect. As a result of technological progress in image verification, it became feasible to decrease its occurrence; however, complete eradication remained unattainable. Various methodologies have been implemented in clinical settings to measure and evaluate the extent of setup mistakes.
View Article and Find Full Text PDFMotivation: Modeling genome-scale metabolic networks (GEMs) helps understand metabolic fluxes in cells at a specific state under defined environmental conditions or perturbations. Elementary flux modes (EFMs) are powerful tools for simplifying complex metabolic networks into smaller, more manageable pathways. However, the enumeration of all EFMs, especially within GEMs, poses significant challenges due to computational complexity.
View Article and Find Full Text PDFAim: The aim of the present study was to examine various factors that may contribute to early crestal bone loss around submerged implants, prior to restoration.
Methods: The research included a collective of 100 implants, procured from 60 participants. We allocated a total of 60 patients into two distinct groups: 20 individuals in the healthy group and 40 individuals in the ECBL group.
Arch Pharm (Weinheim)
April 2024
A series of 1,1'-biphenyl-3-carboxamide and furan-phenyl-carboxamide analogs were synthesized using an optimized scheme and confirmed by H and C nuclear magnetic resonance and high-resolution mass spectrometry techniques. The synthesized peptidomimetics analogs were screened in vitro to understand the inhibitory potential of pancreatic lipase (PL). Analogs were assessed for the PL inhibitory activity based on interactions, geometric complementarity, and docking score.
View Article and Find Full Text PDFWe study the buckling of pressurized spherical shells by Monte Carlo simulations in which the detailed balance is explicitly broken-thereby driving the shell to be active, out of thermal equilibrium. Such a shell typically has either higher (active) or lower (sedate) fluctuations compared to one in thermal equilibrium depending on how the detailed balance is broken. We show that, for the same set of elastic parameters, a shell that is not buckled in thermal equilibrium can be buckled if turned active.
View Article and Find Full Text PDFPhys Rev Lett
September 2023
We investigate the spectral properties of buoyancy-driven bubbly flows. Using high-resolution numerical simulations and phenomenology of homogeneous turbulence, we identify the relevant energy transfer mechanisms. We find (a) at a high enough Galilei number (ratio of the buoyancy to viscous forces) the velocity power spectrum shows the Kolmogorov scaling with a power-law exponent -5/3 for the range of scales between the bubble diameter and the dissipation scale (η).
View Article and Find Full Text PDFMost materials exhibit creep memory under the action of a constant load. The memory behavior is governed by Andrade's creep law, which also has an inherent connection with the Omori-Utsu law of earthquake aftershocks. Both empirical laws lack a deterministic interpretation.
View Article and Find Full Text PDFCell Host Microbe
February 2023
Malaria transmission to mosquitoes requires a developmental switch in asexually dividing blood-stage parasites to sexual reproduction. In Plasmodium berghei, the transcription factor AP2-G is required and sufficient for this switch, but how a particular sex is determined in a haploid parasite remains unknown. Using a global screen of barcoded mutants, we here identify genes essential for the formation of either male or female sexual forms and validate their importance for transmission.
View Article and Find Full Text PDFPhilos Trans A Math Phys Eng Sci
March 2022
The rate of collision and the relative velocities of the colliding particles in turbulent flows are a crucial part of several natural phenomena, e.g. rain formation in warm clouds and planetesimal formation in protoplanetary discs.
View Article and Find Full Text PDFCurr Opin Microbiol
October 2021
Genome scale metabolic models (GEMs) offer a powerful means of integrating genome and biochemical information on an organism to make testable predictions of metabolic functions at different conditions and to systematically predict essential genes that may be targeted by drugs. This review describes how Plasmodium GEMs have become increasingly more accurate through the integration of omics and experimental genetic data. We also discuss how GEMs contribute to our increasing understanding of how Plasmodium metabolism is reprogrammed between life cycle stages.
View Article and Find Full Text PDFEur Phys J E Soft Matter
November 2020
We present a direct numerical simulation (DNS) study of buoyancy-driven bubbly flows in two dimensions. We employ the volume of fluid (VOF) method to track the bubble interface. To investigate the spectral properties of the flow, we derive the scale-by-scale energy budget equation.
View Article and Find Full Text PDFUnderstanding the adaptive responses of individual bacterial strains is crucial for microbiome engineering approaches that introduce new functionalities into complex microbiomes, such as xenobiotic compound metabolism for soil bioremediation. Adaptation requires metabolic reprogramming of the cell, which can be captured by multi-omics, but this data remains formidably challenging to interpret and predict. Here we present a new approach that combines genome-scale metabolic modeling with transcriptomics and exometabolomics, both of which are common tools for studying dynamic population behavior.
View Article and Find Full Text PDFAn amendment to this paper has been published and can be accessed via a link at the top of the paper.
View Article and Find Full Text PDFPlasmodium gene functions in mosquito and liver stages remain poorly characterized due to limitations in the throughput of phenotyping at these stages. To fill this gap, we followed more than 1,300 barcoded P. berghei mutants through the life cycle.
View Article and Find Full Text PDFWe present direct numerical simulation of heavy inertial particles (dust) immersed in two-dimensional turbulent flow (gas). The dust particles are modeled as monodispersed heavy particles capable of modifying the flow through two-way coupling. By varying the Stokes number (St) and the mass-loading parameter (ϕ_{m}), we study the clustering phenomenon and the gas phase kinetic energy spectra.
View Article and Find Full Text PDFMost of the current applications of acoustic cavitation use bubble clusters that exhibit multibubble dynamics. This necessitates a complete understanding of the mutual nonlinear coupling between individual bubbles. In this study, strong nonlinear coupling is investigated in bubble pairs which is the simplest case of a bubble-cluster.
View Article and Find Full Text PDFThe ever-increasing availability of transcriptomic and metabolomic data can be used to deeply analyze and make ever-expanding predictions about biological processes, as changes in the reaction fluxes through genome-wide pathways can now be tracked. Currently, constraint-based metabolic modeling approaches, such as flux balance analysis (FBA), can quantify metabolic fluxes and make steady-state flux predictions on a genome-wide scale using optimization principles. However, relating the differential gene expression or differential metabolite abundances in different physiological states to the differential flux profiles remains a challenge.
View Article and Find Full Text PDFNonalcoholic fatty liver disease (NAFLD) is associated with metabolic syndromes spanning a wide spectrum of diseases, from simple steatosis to the more complex nonalcoholic steatohepatitis. To identify the deregulation that occurs in metabolic processes at the molecular level that give rise to these various NAFLD phenotypes, algorithms such as pathway enrichment analysis (PEA) can be used. These analyses require the use of predefined pathway maps, which are composed of reactions describing metabolic processes/subsystems.
View Article and Find Full Text PDFThe characteristic time-dependent viscosity of the intergranular pore-fluid in Buckingham's grain-shearing (GS) model [Buckingham, J. Acoust. Soc.
View Article and Find Full Text PDFMany of the most interesting complex media are non-Newtonian and exhibit time-dependent behavior of thixotropy and rheopecty. They may also have temporal responses described by power laws. The material behavior is represented by the relaxation modulus and the creep compliance.
View Article and Find Full Text PDFNon-alcoholic fatty liver disease (NAFLD) is a consequence of sedentary life style and high fat diets with an estimated prevalence of about 30% in western countries. It is associated with insulin resistance, obesity, glucose intolerance and drug toxicity. Additionally, polymorphisms within, e.
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