BONCAT-iTRAQ Labelling Reveals Molecular Markers of Adaptive Responses in to Pyrimethamine Treatment.

We employed a BONCAT-iTRAQ labelling approach to investigate newly synthesised proteins (NSPs) in subjected to varying concentrations of the antifolate drug pyrimethamine. Our results reveal that numerous NSPs exhibited altered expression levels in response to the drug, with significant upregulation observed at higher concentrations. Key proteins involved in protein synthesis, stress responses, energy metabolism, and cytoskeletal dynamics were identified, indicating that undergoes complex adaptive responses to pyrimethamine treatment.

Optimizing Camera Exposure Time for Automotive Applications.

Camera-based object detection is integral to advanced driver assistance systems (ADAS) and autonomous vehicle research, and RGB cameras remain indispensable for their spatial resolution and color information. This study investigates exposure time optimization for such cameras, considering image quality in dynamic ADAS scenarios. Exposure time, the period during which the camera sensor is exposed to light, directly influences the amount of information captured.

A Study on Data Selection for Object Detection in Various Lighting Conditions for Autonomous Vehicles.

In recent years, significant advances have been made in the development of Advanced Driver Assistance Systems (ADAS) and other technology for autonomous vehicles. Automated object detection is a crucial component of autonomous driving; however, there are still known issues that affect its performance. For automotive applications, object detection algorithms are required to perform at a high standard in all lighting conditions; however, a major problem for object detection is poor performance in low-light conditions due to objects being less visible.

Beyond Discharge Disposition: A Scoping Review on Sociodemographic Disparities in Rehabilitation Use After Hip and Knee Arthroplasty.

Objective: The aims of this scoping review were to summarize the evidence regarding sex, racial, ethnic, geographic, and socioeconomic disparities in post-acute rehabilitation following total hip arthroplasty (THA) and knee arthroplasty (TKA).

Methods: Literature searches were conducted in Ovid MEDLINE, EMBASE, CINAHL, Web of Science, and PEDro. Studies were included if they were original research articles published 1993 or later; used data from the US; included patients after THA and/or TKA; presented results according to relevant sociodemographic variables, including sex, race, ethnicity, geography, or socioeconomic status; and studied the utilization of post-acute rehabilitation as an outcome.

Rapid genotyping of Toxoplasma gondii isolates via Nanopore-based multi-locus sequencing.

Toxoplasma gondii is an obligate intracellular parasite associated with severe disease, especially in the immunosuppressed. It is also a cause of congenital malformation and abortion in both animals and humans and is considered one of the most important foodborne pathogens worldwide with different strains showing variable distribution and differing pathogenicity. Thus, strain-level differentiation of T.

Clemastine/tamoxifen hybrids as easily accessible antileishmanial drug leads.

A library of hybrid molecules is developed based on the common chemical features shared by clemastine and tamoxifen both of which are well known for their antileishmanial activities. In the initial screening against major and promastigotes, as well as cytotoxicity assays using HepG2 cells, several hybrids showed submicromolar activity against the parasite and no toxicity against human cells. The compounds with an EC < 2 μM against promastigotes of both species and a selectivity index >10 were further characterized against intracellular amastigotes as well as promastigotes of species that cause both visceral and cutaneous leishmaniasis, such as and , respectively.

Impact of ISP Tuning on Object Detection.

In advanced driver assistance systems (ADAS) or autonomous vehicle research, acquiring semantic information about the surrounding environment generally relies heavily on camera-based object detection. Image signal processors (ISPs) in cameras are generally tuned for human perception. In most cases, ISP parameters are selected subjectively and the resulting image differs depending on the individual who tuned it.

Inhibition of HSP90 distinctively modulates the global phosphoproteome of developmental stages.

In the unicellular parasites spp., the etiological agents of leishmaniasis, a complex infectious disease that affects 98 countries in 5 continents, chemical inhibition of HSP90 protein leads to differentiation from promastigote to amastigote stage. Recent studies indicate potential role for protein phosphorylation in the life cycle control of .

Toxoplasma ceramide synthases: Gene duplication, functional divergence, and roles in parasite fitness.

Toxoplasma gondii is an obligate, intracellular apicomplexan protozoan parasite of both humans and animals that can cause fetal damage and abortion and severe disease in the immunosuppressed. Sphingolipids have indispensable functions as signaling molecules and are essential and ubiquitous components of eukaryotic membranes that are both synthesized and scavenged by the Apicomplexa. Ceramide is the precursor for all sphingolipids, and here we report the identification, localization and analyses of the Toxoplasma ceramide synthases TgCerS1 and TgCerS2.

Evaluating a large language model's ability to solve programming exercises from an introductory bioinformatics course.

Computer programming is a fundamental tool for life scientists, allowing them to carry out essential research tasks. However, despite various educational efforts, learning to write code can be a challenging endeavor for students and researchers in life-sciences disciplines. Recent advances in artificial intelligence have made it possible to translate human-language prompts to functional code, raising questions about whether these technologies can aid (or replace) life scientists' efforts to write code.

Disruption of the inositol phosphorylceramide synthase gene affects Trypanosoma cruzi differentiation and infection capacity.

Sphingolipids (SLs) are essential components of all eukaryotic cellular membranes. In fungi, plants and many protozoa, the primary SL is inositol-phosphorylceramide (IPC). Trypanosoma cruzi is a protozoan parasite that causes Chagas disease (CD), a chronic illness for which no vaccines or effective treatments are available.

Assessment of lytic cycle and the impact of a gene deletion using 3D label-free optical diffraction holotomography.

is a widespread single-celled intracellular eukaryotic apicomplexan protozoan parasite primarily associated with mammalian foetal impairment and miscarriage, including in humans. Is estimated that approximately one third of the human population worldwide is infected by this parasite. Here we used cutting-edge, label-free 3D quantitative optical diffraction holotomography to capture and evaluate the lytic cycle (invasion, proliferation and egress) in real-time based on the refractive index distribution.

Pedestrian Crossing Intention Forecasting at Unsignalized Intersections Using Naturalistic Trajectories.

Interacting with other roads users is a challenge for an autonomous vehicle, particularly in urban areas. Existing vehicle systems behave in a reactive manner, warning the driver or applying the brakes when the pedestrian is already in front of the vehicle. The ability to anticipate a pedestrian's crossing intention ahead of time will result in safer roads and smoother vehicle maneuvers.

The Gene Ontology knowledgebase in 2023.

The Gene Ontology (GO) knowledgebase (http://geneontology.org) is a comprehensive resource concerning the functions of genes and gene products (proteins and noncoding RNAs). GO annotations cover genes from organisms across the tree of life as well as viruses, though most gene function knowledge currently derives from experiments carried out in a relatively small number of model organisms.

Genome deletions to overcome the directed loss of gene function in .

With the global reach of the Neglected Tropical Disease leishmaniasis increasing, coupled with a tiny armory of therapeutics which all have problems with resistance, cost, toxicity and/or administration, the validation of new drug targets in the causative insect vector borne protozoa spp is more important than ever. Before the introduction of CRISPR Cas9 technology in 2015 genetic validation of new targets was carried out largely by targeted gene knockout through homologous recombination, with the majority of genes targeted (~70%) deemed non-essential. In this study we exploit the ready availability of whole genome sequencing technology to reanalyze one of these historic cell lines, a knockout in the catalytic subunit of serine palmitoyltransferase (LCB2), which causes a complete loss of sphingolipid biosynthesis but remains viable and infective.

A standardized nomenclature for mammalian histone genes.

Histones have a long history of research in a wide range of species, leaving a legacy of complex nomenclature in the literature. Community-led discussions at the EMBO Workshop on Histone Variants in 2011 resulted in agreement amongst experts on a revised systematic protein nomenclature for histones, which is based on a combination of phylogenetic classification and historical symbol usage. Human and mouse histone gene symbols previously followed a genome-centric system that was not applicable across all vertebrate species and did not reflect the systematic histone protein nomenclature.

Illuminating Host-Parasite Interaction at the Cellular and Subcellular Levels with Infrared Microspectroscopy.

() is an opportunistic protozoan that can cause brain infection and other serious health consequences in immuno-compromised individuals. This parasite has a remarkable ability to cross biological barriers and exploit the host cell microenvironment to support its own survival and growth. Recent advances in label-free spectroscopic imaging techniques have made it possible to study biological systems at a high spatial resolution.

Transcriptome-Wide Identification of Coding and Noncoding RNA-Binding Proteins Defines the Comprehensive RNA Interactome of Leishmania mexicana.

Proteomic profiling of RNA-binding proteins in is currently limited to polyadenylated mRNA-binding proteins, leaving proteins that interact with nonadenylated RNAs, including noncoding RNAs and pre-mRNAs, unidentified. Using a combination of unbiased orthogonal organic phase separation methodology and tandem mass tag-labeling-based high resolution quantitative proteomic mass spectrometry, we robustly identified 2,417 RNA-binding proteins, including 1289 putative novel non-poly(A)-RNA-binding proteins across the two main life cycle stages. Eight out of 20 deubiquitinases, including the recently characterized L.

Chalcones identify cTXNPx as a potential antileishmanial drug target.

With current drug treatments failing due to toxicity, low efficacy and resistance; leishmaniasis is a major global health challenge that desperately needs new validated drug targets. Inspired by activity of the natural chalcone 2',6'-dihydroxy-4'-methoxychalcone (DMC), the nitro-analogue, 3-nitro-2',4',6'- trimethoxychalcone (NAT22, 1c) was identified as potent broad spectrum antileishmanial drug lead. Structural modification provided an alkyne containing chemical probe that labelled a protein within the parasite that was confirmed as cytosolic tryparedoxin peroxidase (cTXNPx).

The Histidine Ammonia Lyase of Trypanosoma cruzi Is Involved in Acidocalcisome Alkalinization and Is Essential for Survival under Starvation Conditions.

Trypanosoma cruzi, the agent of Chagas disease, accumulates polyphosphate (polyP) and Ca inside acidocalcisomes. The alkalinization of this organelle stimulates polyP hydrolysis and Ca release. Here, we report that histidine ammonia lyase (HAL), an enzyme that catalyzes histidine deamination with production of ammonia (NH) and urocanate, is responsible for acidocalcisome alkalinization.