Publications by authors named "Stefan Weidt"

Liposomal amphotericin B is an important frontline drug for the treatment of visceral leishmaniasis, a neglected disease of poverty. The mechanism of action of amphotericin B (AmB) is thought to involve interaction with ergosterol and other ergostane sterols, resulting in disruption of the integrity and key functions of the plasma membrane. Emergence of clinically refractory isolates of Leishmania donovani and L.

View Article and Find Full Text PDF

Fermentation monitoring is a powerful tool for bioprocess development and optimization. On-line metabolomics is a technology that is starting to gain attention as a bioprocess monitoring tool, allowing the direct measurement of many compounds in the fermentation broth at a very high time resolution. In this work, targeted on-line metabolomics was used to monitor 40 metabolites of interest during three Escherichia coli succinate production fermentation experiments every 5 min with a triple quadrupole mass spectrometer.

View Article and Find Full Text PDF
Article Synopsis
  • Dilated cardiomyopathy (iDCM) is a significant disease affecting both dogs and humans, being the second leading cause of heart failure in dogs and can lead to sudden cardiac death.
  • This study compared the plasma metabolome of 12 dogs with iDCM to 8 healthy dogs, utilizing advanced mass-spectrometry techniques to identify 272 metabolites.
  • Findings revealed notable changes in metabolite concentrations (like amino acids and lipids) associated with iDCM, paving the way for better understanding and monitoring of this condition in the future.
View Article and Find Full Text PDF

Motivation: Liquid Chromatography Tandem Mass Spectrometry experiments aim to produce high-quality fragmentation spectra, which can be used to annotate metabolites. However, current Data-Dependent Acquisition approaches may fail to collect spectra of sufficient quality and quantity for experimental outcomes, and extend poorly across multiple samples by failing to share information across samples or by requiring manual expert input.

Results: We present TopNEXt, a real-time scan prioritization framework that improves data acquisition in multi-sample Liquid Chromatography Tandem Mass Spectrometry metabolomics experiments.

View Article and Find Full Text PDF

Data-Dependent and Data-Independent Acquisition modes (DDA and DIA, respectively) are both widely used to acquire MS2 spectra in untargeted liquid chromatography tandem mass spectrometry (LC-MS/MS) metabolomics analyses. Despite their wide use, little work has been attempted to systematically compare their MS/MS spectral annotation performance in untargeted settings due to the lack of ground truth and the costs involved in running a large number of acquisitions. Here, we present a systematic comparison of these two acquisition methods in untargeted metabolomics by extending our Virtual Metabolomics Mass Spectrometer (ViMMS) framework with a DIA module.

View Article and Find Full Text PDF

This study examines whether maternal low ω6:ω3 ratio diet and offspring SW supplementation can improve offspring immunity and performance by elucidating the effects on piglet serum proteome. A total of 16 sows were given either a standard (CR, 13:1) or low ω6:ω3 ratio diet (LR, 4:1) during pregnancy and lactation and their male weaned piglets were supplemented with SW powder (4 g/kg, SW) or not (CT) in a 21-day post-weaning (PW) diet. Four PW piglet groups were then identified based on dam and piglet treatment, namely CRCT, CRSW, LRCT, and LRSW (n = 10 each).

View Article and Find Full Text PDF
Article Synopsis
  • The study investigates how a long-term low ω6:ω3 dietary ratio in sows, along with seaweed supplementation in their offspring, affects the intestinal health and growth of piglets by analyzing the proteins in their ileum.
  • Sows were divided into two diet groups: a control group with a high ω6:ω3 ratio and a treatment group with a low ratio, while piglets were further divided based on their seaweed supplementation.
  • Results revealed that the low ω6:ω3 diet positively impacted protein synthesis and cell growth in the piglets, while seaweed improved gut development and reduced inflammation but affected fat absorption differently depending on the maternal diet.
View Article and Find Full Text PDF
Article Synopsis
  • Amphotericin B is increasingly used to treat leishmaniasis; researchers studied 14 Leishmania mexicana lines and one L. infantum line for resistance to this drug and nystatin.
  • Resistance correlated with changes in sterols, notably a switch from the wild-type sterol ergosta-5,7,24-trienol to other intermediates, due to mutations in specific genes related to sterol biosynthesis.
  • Some resistant lines displayed altered virulence, with a few showing increased virulence despite their resistance to Amphotericin B, highlighting potential risks in clinical treatment.
View Article and Find Full Text PDF

The chloroquine resistance transporter, PfCRT, is an essential factor during intraerythrocytic development of the human malaria parasite Plasmodium falciparum. PfCRT resides at the digestive vacuole of the parasite, where hemoglobin taken up by the parasite from its host cell is degraded. PfCRT can acquire several mutations that render PfCRT a drug transporting system expelling compounds targeting hemoglobin degradation from the digestive vacuole.

View Article and Find Full Text PDF
Article Synopsis
  • - This study explored how a low dietary ω6:ω3 fatty acids (FAs) ratio affects the protein profile in the plasma of sows during gestation and lactation, comparing a control group to a low ratio group.
  • - High-resolution mass spectrometry identified 379 proteins, with 4 showing significant differences between the two dietary treatments during gestation, and others indicating changes related to lipoproteins and stress responses by the end of lactation.
  • - Findings suggest that a lower ω6:ω3 FAs ratio enhances the cellular defense against stressors in sows, particularly oxidative stress, by modifying proteins associated with protective mechanisms during critical reproductive phases.
View Article and Find Full Text PDF

The formation of a protein layer "corona" on the nanoparticle surface upon entry into a biological environment was shown to strongly influence the interactions with cells, especially affecting the uptake of nanomedicines. In this work, we present the impact of the protein corona on the uptake of PEGylated zein micelles by cancer cells, macrophages, and dendritic cells. Zein was successfully conjugated with poly(ethylene glycol) (PEG) of varying chain lengths (5K and 10K) and assembled into micelles.

View Article and Find Full Text PDF
Article Synopsis
  • * The research aimed to analyze the serum metabolome of 12 dogs infected with babesiosis compared to 12 healthy dogs, using advanced chromatography techniques, leading to the identification of 295 metabolites.
  • * Findings revealed various metabolic pathways involved in the disease, highlighting the potential for using metabolomics to better understand host-pathogen interactions and the mechanisms behind babesiosis in dogs.
View Article and Find Full Text PDF

Tandem mass spectrometry (LC-MS/MS) is widely used to identify unknown ions in untargeted metabolomics. Data-dependent acquisition (DDA) chooses which ions to fragment based upon intensities observed in MS1 survey scans and typically only fragments a small subset of the ions present. Despite this inefficiency, relatively little work has addressed the development of new DDA methods, partly due to the high overhead associated with running the many extracts necessary to optimize approaches in busy MS facilities.

View Article and Find Full Text PDF

Owing to the importance and clinical diversity of Leishmania infantum, studying its virulence factors is promising for understanding the relationship between parasites and hosts. In the present study, differentially abundant proteins from strains with different degrees of virulence in promastigote and amastigote forms were compared using two quantitative proteomics techniques, differential gel electrophoresis and isobaric mass tag labeling, followed by identification by mass spectrometry. A total of 142 proteins were identified: 96 upregulated and 46 downregulated proteins in the most virulent strain compared to less virulent.

View Article and Find Full Text PDF

The success of forensic investigations involving fatalities very often depends on the establishment of the correct timeline of events. Currently used methods for estimating the postmortem interval (PMI) are mostly dependent on the professional and tacit experience of the investigator, and often with poor reliability in the absence of robust biological markers. The aim of this study was to investigate the potential of metabolomic approaches to highlight molecular markers for PMI.

View Article and Find Full Text PDF

Coloration has been associated with multiple biologically relevant traits that drive adaptation and diversification in many taxa. However, despite the great diversity of colour patterns present in amphibians the underlying molecular basis is largely unknown. Here, we use insight from a highly colour-variable lineage of the European fire salamander (Salamandra salamandra bernardezi) to identify functional associations with striking variation in colour morph and pattern.

View Article and Find Full Text PDF

Liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) is widely used in identifying small molecules in untargeted metabolomics. Various strategies exist to acquire MS/MS fragmentation spectra; however, the development of new acquisition strategies is hampered by the lack of simulators that let researchers prototype, compare, and optimize strategies before validations on real machines. We introduce Virtual Metabolomics Mass Spectrometer (ViMMS), a metabolomics LC-MS/MS simulator framework that allows for scan-level control of the MS2 acquisition process in silico.

View Article and Find Full Text PDF

Background: Carboxymethyl lysine is an advanced glycation end product of interest as a potential biomarker of cardiovascular and other diseases. Available methods involve ELISA, with potential interference, or isotope dilution mass spectrometry (IDMS), with low-throughput sample preparation.

Methods: A high-throughput sample preparation method based on 96-well plates was developed.

View Article and Find Full Text PDF

Amphotericin B is an increasingly important tool in efforts to reduce the global disease burden posed by Leishmania parasites. With few other chemotherapeutic options available for the treatment of leishmaniasis, the potential for emergent resistance to this drug is a considerable threat. Here we characterised four novel amphotericin B-resistant Leishmania mexicana lines.

View Article and Find Full Text PDF
Article Synopsis
  • Transketolase (TKT) is an enzyme in the pentose phosphate pathway, and its removal in Leishmania mexicana led to non-virulent strains in mice, despite no impact on its growth in lab cultures.
  • The Δtkt cells showed increased susceptibility to oxidative stress and drugs, alongside significant metabolic changes, such as reduced central carbon metabolism and glycolysis, even with only minor gene expression changes.
  • The study also explored how TKT's location in the cell affects its function; modifying the enzyme's location did not alter glucose processing, indicating that its function is more complex than just where it is found within the cell.
View Article and Find Full Text PDF

Amphotericin B has emerged as the therapy of choice for use against the leishmaniases. Administration of the drug in its liposomal formulation as a single injection is being promoted in a campaign to bring the leishmaniases under control. Understanding the risks and mechanisms of resistance is therefore of great importance.

View Article and Find Full Text PDF

Unlabelled: Leishmania parasites multiply and develop in the gut of a sand fly vector in order to be transmitted to a vertebrate host. During this process they encounter and exploit various nutrients, including sugars, and amino and fatty acids. We have previously generated a mutant Leishmania line that is deficient in glucose transport and which displays some biologically important phenotypic changes such as reduced growth in axenic culture, reduced biosynthesis of hexose-containing virulence factors, increased sensitivity to oxidative stress, and dramatically reduced parasite burden in both insect vector and macrophage host cells.

View Article and Find Full Text PDF

Introduction: Combined infections from and are a leading cause of death in the developed world. Evidence suggests that enhances the virulence of -hyphae penetrate through tissue barriers, while tightly associates with the hyphae to obtain entry to the host organism. Indeed, in a biofilm state, enhances the antimicrobial resistance characteristics of .

View Article and Find Full Text PDF

Mastitis, inflammation of the mammary gland, is the most common and costly disease of dairy cattle in the western world. It is primarily caused by bacteria, with Streptococcus uberis as one of the most prevalent causative agents. To characterize the proteome during Streptococcus uberis mastitis, an experimentally induced model of intramammary infection was used.

View Article and Find Full Text PDF
Article Synopsis
  • Lesch-Nyhan disease (LND) results from mutations in the HPRT gene, which is vital for recycling purine nucleotides, leading to neurological issues.
  • Researchers created HPRT knock-out rats to explore the effects of this mutation on brain function, finding them viable and fertile but with notable metabolic changes in brain biochemistry.
  • Analysis showed decreased dopamine levels in these rats, reflecting similar deficits in humans with LND, suggesting this model could help further understand the disease's impact on neural function and behavior.
View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_session2u85rflklp8qot802i5sk3ump2fung97): Failed to open stream: No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 177

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)

Filename: Session/Session.php

Line Number: 137

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once