Biology subjects

Wahlgren, M.

Publications and source records attributed to Wahlgren, M..

3 recordsLinked to original sources

bioRxiv2024

In vitro disintegration of lozenge in oral cavity

The aim of this study is to develop a new in vitro disintegration method for lozenges in the oral cavity (OC) by mimicking physiologically relevant conditions in the OC including saliva flow rate and suction. Disintegration of solid-state dosage forms in the OC can be employed for local absorption in the OC or for delivering to the succeeding parts of the gastrointestinal tract. Understanding the disintegration is important before gaining insight into dissolution and absorption. Here abrasion force and rate exerted on the lozenge during the disintegration are controlled by a texture analyser. We showed that a higher flow rate and more frequent abrasion can lead to a faster disintegration, while variation of the compression force within a range in this study does not affect the disintegration statistically. The results are relevant to different types of consumers with variation in saliva production, for example, people with salivary dysfunction including elderly people. It is also important to consider these effects when formulating flavor and taste of lozenge that can affect consumer perception and consequently suction force and rate or saliva production. We could also observe disintegrated but not dissolved parts of the lozenge by using this apparatus, demonstrating the importance of the correlation between disintegration and dissolution when considering drug absorption in the OC to overcome the challenges of drug clearance from the OC by swallowing.

biophysics↗

bioRxiv2023

Genomic adaptation underlies nutrient-driven reprogramming in the malaria-causing parasite

Parasites often depend on metabolic adaptation to the host environment. An adaptive feature of malaria-causing parasites is digestion of hemoglobin (HB) to acquire amino acids (AAs). Here we describe a link between nutrient availability and translation elongation-dependent regulation of gene expression as an adaptive strategy. We show that, unexpectedly, tRNA expression in P. falciparum does not match the decoding need as tRNAs decoding AAs that are rare in HB are lowly expressed. This discrepancy renders codons of HB-rare AAs inefficiently decoded and transcripts levels negatively correlated with the requirement of HB-rare AAs for protein synthesis, which are consistent with poor codon optimality causing co-translational mRNA decay. Intriguingly, proliferation-related genes have evolved to require a high level of HB-rare AAs in their encoded proteins, thereby allowing the parasite to control its proliferation by repressing protein synthesis of these genes during nutrient stress. We conclude that the parasite modulates translation elongation by maintaining a discordant tRNA profile as a mechanism to exploit variations in AA-composition among genes as an adaptation strategy.

microbiology↗

bioRxiv2019

Membrane integration and topology of RIFIN and STEVOR proteins of the Plasmodium falciparum parasite

The malarial parasite Plasmodium, infects red blood cells by remodeling them and transporting its own proteins to their cell surface. These proteins trigger adhesion of infected cells to uninfected cells (rosetting), and to the vascular endothelium, obstructing blood flow and contributing to pathogenesis. RIFINs (P. falciparum-encoded repetitive interspersed families of polypeptides) and STEVORs (subtelomeric variable open reading frame), are two classes of proteins that are involved in rosetting. Here we study the membrane insertion and topology of three RIFIN and two STEVOR proteins, employing a well-established assay that uses N-linked glycosylation of sites within the protein as a measure to assess the topology a protein adopts when inserted into the ER membrane. Our results indicate that all the proteins tested assume an overall topology of Ncyt-Ccyt, with predicted transmembrane helices TM1 and TM3 integrated into the ER membrane. We also show that the segments predicted as TM2 do not reside in the membrane. Our conclusions are consistent with other recent topology studies on RIFIN and STEVOR proteins.

biochemistry↗