4 research outputs found
Impaired Functions of Peripheral Blood Monocyte Subpopulations in Aged Humans
Aging is associated with increased susceptibility to microbial infections, and monocytes play an important role in microbial defense. In this study, we have identified and compared four subpopulations of monocytes (CD14++(high)CD16−, CD14+(low)CD16−, CD14++(high)CD16+, and CD14+(low)CD16+) in the peripheral blood of young and aged subjects with regard to their numbers, cytokine production, TLR expression, and phosphorylation of ERK1/2 in response to pam3Cys a TLR-1/2 ligand. Proportions and numbers of CD14++(high)CD16+ and CD14+(low)CD16+ monocytes were significantly increased, whereas proportions of CD14+(low)CD16− monocytes were decreased in aged subjects as compared to young subjects. In aged subjects, IL-6 production by all four subsets of monocytes was significantly decreased, whereas TNF-α production was decreased in monocyte subsets, except the CD14+(low)CD16− subset. A significantly reduced expression of TLR1 was observed in CD14++(high)CD16+ and CD14+(low)CD16+ monocyte subsets in aged subjects. Furthermore, following pam3Cys stimulation, ERK1/2 phosphorylation was significantly lower in CD14+(low)CD16+, CD14++(high)CD16+, and CD14+(low)CD16− subsets of monocytes from aged subjects. This is the first study of four subpopulations of monocytes in aging, which demonstrates that their functions are differentially impaired with regard to the production of cytokines, expression of TLR, and signaling via the ERK–MAPK pathway. Finally, changes in the number of monocyte subsets, and impairment of TLR1 expression, TNF-α production, and EK1/2 phosphorylation was more consistent in CD16+ monocyte subsets regardless of expression of CD14high or CD14+low, therefore highlighting the significance of further subdivision of monocytes into four subpopulations
CD16 Expression on Monocytes in Healthy Individuals but Not Schistosome-Infected Patients Is Positively Associated with Levels of Parasite-Specific IgG and IgG1
Human IgG1 antibody responses are associated with protection against Schistosoma haematobium infection and are now a target for schistosome vaccine development. This study aimed to investigate the relationship between total IgG and the IgG subclasses and the monocyte IgG receptor, known as FcγRIIIa or CD16, in schistosome exposed people. Systemic levels of schistosome-specific anti-adult worm total IgG and IgG subclass titres were measured by ELISA in 100 individuals from an S. haematobium endemic area in Zimbabwe and, using parametric statistical methods and regression analysis, related to the levels of CD16 expression on individuals' circulating monocytes, determined via flow cytometry. Monocyte CD16 expression rose with parasite-specific total IgG and IgG1 in healthy participants, but not in schistosome infected patients. Similar to parasite-specific IgG and IgG1, CD16 expression in healthy individuals is associated with protection against schistosome infection. This relationship indicates a mechanistic link between the innate and adaptive immune responses to helminth infection in protection against infection. Further understanding the elements of a protective immune response in schistosomiasis may aid in efforts to develop a protective vaccine against this disease.This work was supported by the World Health Organisation and the Wellcome Trust grant WT082028MA, the Thrasher Research Fund and the Medical Research Council grant LJA-544
DFT Computed Dielectric Response and THz Spectra of Organic Co-Crystals and Their Constituent Components
Towards Measuring the Representation of Subjective Global Opinions in Language Models
Large language models (LLMs) may not equitably represent diverse global
perspectives on societal issues. In this paper, we develop a quantitative
framework to evaluate whose opinions model-generated responses are more similar
to. We first build a dataset, GlobalOpinionQA, comprised of questions and
answers from cross-national surveys designed to capture diverse opinions on
global issues across different countries. Next, we define a metric that
quantifies the similarity between LLM-generated survey responses and human
responses, conditioned on country. With our framework, we run three experiments
on an LLM trained to be helpful, honest, and harmless with Constitutional AI.
By default, LLM responses tend to be more similar to the opinions of certain
populations, such as those from the USA, and some European and South American
countries, highlighting the potential for biases. When we prompt the model to
consider a particular country's perspective, responses shift to be more similar
to the opinions of the prompted populations, but can reflect harmful cultural
stereotypes. When we translate GlobalOpinionQA questions to a target language,
the model's responses do not necessarily become the most similar to the
opinions of speakers of those languages. We release our dataset for others to
use and build on. Our data is at
https://huggingface.co/datasets/Anthropic/llm_global_opinions. We also provide
an interactive visualization at https://llmglobalvalues.anthropic.com