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Developmentally cascading structures do not lose evolutionary potential, but compound developmental instability in rat molars.
bioRxiv
January 2025
Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
Increasing variability down serially segmented structures, such as mammalian molar teeth and vertebrate limb segments, is a much-replicated pattern. The same phenotypic pattern has conflicting interpretations at different evolutionary scales. Macroevolutionary patterns are thought to reflect greater evolutionary potential in later-forming segments, but microevolutionary patterns are thought to reflect less evolutionary potential and greater phenotypic plasticity.
View Article and Find Full Text PDFInitiation of primary T cell-B cell interactions and extrafollicular antibody responses in an organized microphysiological model of the human lymph node.
bioRxiv
January 2025
Department of Chemistry, 409 McCormick Road, University of Virginia, Charlottesville, VA 22904.
Antibody production is central to protection against new pathogens and cancers, as well as to certain forms of autoimmunity. Antibodies often originate in the lymph node (LN), specifically at the extrafollicular border of B cell follicles, where T and B lymphocytes physically interact to drive B cell maturation into antibody-secreting plasmablasts. In vitro models of this process are sorely needed to predict aspects of the human immune response.
View Article and Find Full Text PDFThe role of spatial location in irrelevant speech revisited: A preregistered replication study.
J Exp Psychol Learn Mem Cogn
December 2024
Technical University of Darmstadt, Institute of Psychology.
The goal of the present investigation was to perform a registered replication of Jones and Macken's (1995b) study, which showed that the segregation of a sequence of sounds to distinct locations reduced the disruptive effect on serial recall. Thereby, it postulated an intriguing connection between auditory stream segregation and the cognitive mechanisms underlying the irrelevant speech effect. Specifically, it was found that a sequence of changing utterances was less disruptive in stereophonic presentation, allowing each auditory object (letters) to be allocated to a unique location (right ear, left ear, center), compared to when the same sounds were played monophonically.
View Article and Find Full Text PDFPET/CT guided tuberculosis treatment shortening: a randomized trial.
medRxiv
October 2024
Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA.
Six months of chemotherapy using current agents is standard of care for pulmonary, drug-sensitive tuberculosis (TB), even though some are believed to be cured more rapidly and others require longer therapy. Understanding what factors determine the length of treatment required for durable cure in individual patients would allow individualization of treatment durations, provide better clinical tools to determine the of appropriate duration of new regimens, as well as reduce the cost of large Phase III studies to determine the optimal combinations to use in TB control programs. We conducted a randomized clinical trial in South Africa and China that recruited 704 participants with newly diagnosed, drug-sensitive pulmonary tuberculosis and stratified them based on radiographic disease characteristics as assessed by FDG PET/CT scan readers.
View Article and Find Full Text PDFDynamic PK/PD Infection Models for the Development and Optimisation of Antimicrobial Regimens: A Narrative Review.
Antibiotics (Basel)
December 2024
Centre for Clinical Research (UQCCR), Faculty of Medicine, The University of Queensland, Brisbane, QLD 4029, Australia.
The antimicrobial concentration-time profile in humans affects antimicrobial activity, and as such, it is critical for preclinical infection models to simulate human-like dynamic concentration-time profiles for maximal translatability. This review discusses the setup, principle, and application of various dynamic PK/PD infection models commonly used in the development and optimisation of antimicrobial treatment regimens. It covers the commonly used dynamic infection models, including the one-compartment model, hollow fibre infection model, biofilm model, bladder infection model, and aspergillus infection model.
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