craft t cell

Mediterranean diets may be neuroprotective and prevent cognitive decline relative to Western diets, however the underlying biology is poorly understood. We assessed the effects of Western versus Mediterranean-like diets on RNAseq-generated transcriptional profiles in lateral temporal cortex and their relationships with longitudinal changes in neuroanatomy, circulating monocyte gene expression, and observations of social isolation and anxiety in 38 socially-housed, middle-aged female cynomolgus macaques (Macaca fascicularis)...

Naked mole-rats (NMRs) are best known for their extreme longevity and cancer resistance, suggesting that their immune system might have evolved to facilitate these phenotypes. Natural killer (NK) and T cells have evolved to detect and destroy cells infected with pathogens and to provide an early response to malignancies. While it is known that NMRs lack NK cells, likely lost during evolution, little is known about their T-cell subsets in terms of the evolution of the genes that regulate their function, their clonotypic diversity, and the thymus where they mature...

Recent strides in immunotherapy have illuminated the crucial role of CTLA-4 and PD-1/PD-L1 pathways in contemporary oncology, presenting both promises and challenges in response rates and adverse effects. This study employs a computational biology tool (in silico approach) to craft aptamers capable of binding to dual receptors, namely, inhibitory CTLA4 and NKG2A, thereby unleashing both T and NK cells and enhancing CD8+ T and NK cell functions for tumor cell lysis. Computational analysis highlighted AYA22T-R2-13 with HADDOCK scores of -78...

Chimeric antigen receptor (CAR) T cell technology has ushered in a new era of immunotherapy, enabling the targeting of a broad range of surface antigens, surpassing the limitations of traditional T cell epitopes. Despite the wide range of non-protein tumor-associated antigens, the advancement in crafting CAR T cells for these targets has been limited. Owing to an evolutionary defect in the CMP-Neu5Ac hydroxylase (CMAH) that abolishes the synthesis of CMP-Neu5Gc from CMP-Neu5Ac, Neu5Gc is generally absent in human tissues...

The availability of a wide range of flavored e-cigarettes is one of the primary reasons for vaping initiation and persistent use among adolescents and young people. This plethora of flavors available on the market are crafted using different flavoring agents such as cinnamaldehyde, vanillin, benzaldehyde, ethyl maltol, menthol, and dimethylpyrazine. Recent studies have brought to light the potential risks associated with e-cigarette flavoring agents and their effects on various organ systems, both with and without nicotine...

T follicular helper (Tfh) cells specialize in helping B cells and are therefore critical contributors to the generation of humoral immunity. Tfh cells aid immunoglobulin class-switch recombination and support the germinal center response, thereby promoting immunoglobulin affinity maturation and the generation of humoral immune memory. Although their primary function is to promote B cell responses, Tfh cells also display phenotypic and functional diversity determined by the immunological and spatial contexts from which they emerge...

Co-assembling peptides can be crafted into supramolecular biomaterials for use in biotechnological applications, such as cell culture scaffolds, drug delivery, biosensors, and tissue engineering. Peptide co-assembly refers to the spontaneous organization of two different peptides into a supramolecular architecture. Here we use molecular dynamics simulations to quantify the effect of anionic amino acid type on co-assembly dynamics and nanofiber structure in binary CATCH(+/-) peptide systems. CATCH peptide sequences follow a general pattern: CQCFCFCFCQC, where all C's are either a positively charged or a negatively charged amino acid...

INTRODUCTION: Mediterranean diets may be neuroprotective and prevent cognitive decline relative to Western diets, however the underlying biology is poorly understood. METHODS: We assessed the effects of Western vs. Mediterranean-like diets on RNAseq generated transcriptional profiles in temporal cortex and their relationships with changes in MRI neuroimaging phenotypes, circulating monocyte gene expression, and observations of social isolation and anxiety in 38 socially-housed, middle-aged female cynomolgus macaques...

Deleterious germline RUNX1 variants cause the autosomal dominant disease familial platelet disorder with associated myeloid malignancy (FPDMM), characterized by thrombocytopenia, platelet functional defects and predisposition to hematologic malignancies (HMs). We launched a FPDMM natural history study and, from January 2019-December 2021, enrolled 214 participants, including 111 patients with 39 different RUNX1 variants from 45 unrelated families. Of those with available data, 91% (70/77) had thrombocytopenia, 100% (18/18) had abnormal platelet aggregometry, 46% (16/35) had platelets with decreased dense granules, and 51% (28/55) had abnormal bleeding scores...

Studies over the last 100 years have suggested a link between inflammation, infectious disease, and Alzheimer's Disease (AD). Understanding how the immune system changes during the development of AD may facilitate new treatments. Here, we studied an aging cohort who had been assessed for AD pathology with amyloid positron emission tomography and cognitive testing, and conducted high dimensional flow cytometry on peripheral blood mononuclear and cerebrospinal fluid cells. Participants were assigned a classification of being amyloid negative cognitively normal, amyloid positive cognitively normal (APCN), or amyloid positive mild cognitive impairment (APMCI), an early stage of AD...

Lipid-soluble components in late-cutting alfalfa are linked to beneficial immune and microbiota responses in mouse challenge models; therefore, responses in a comparative poultry Eimeria challenge model were investigated. The study objective was to evaluate performance, immunity, and the cecal microbiota in broilers fed ground hay or lipid-soluble extract from late (fifth) cutting alfalfa during Eimeria challenge. At hatch, 432 Ross 708 broilers were placed in 24 floor pens (18 birds/pen) and assigned to 3 isocaloric/isonitrogenous dietary treatments consisting of control, 5% ground hay, or 0...

OBJECTIVE: This review describes the comprehensive portrait of tumor microenvironment (TME). Additionally, we provided a panoramic perspective on the transformation and functions of the diverse constituents in TME, and the underlying mechanisms of drug resistance, beginning with the immune cells and metabolic dynamics within TME. Lastly, we summarized the most auspicious potential therapeutic strategies. RESULTS: TME is a unique realm crafted by malignant cells to withstand the onslaught of endogenous and exogenous therapies...

Cutaneous lupus erythematosus (CLE) is a disfiguring autoimmune skin disease characterized by an inflammatory infiltrate rich in T cells, which are strongly implicated in tissue damage. How these cells adapt to the skin environment and promote tissue inflammation and damage is not known. In lupus nephritis, we have previously identified an inflammatory gene program in kidney-infiltrating T cells that is dependent on hypoxia-inducible factor-1 (HIF-1), a transcription factor critical for the cellular and developmental response to hypoxia as well as inflammation-associated signals...

The stereochemical properties of N -acyl-5 H -dibenzo[ b , d ]azepin-7(6 H )-ones ( 2a - c ), which inhibit potassium channels in T cells, were examined by freezing their conformational change due to 4-methyl substitution. N -Acyl-5 H -dibenzo[ b , d ]azepin-7(6 H )-ones exist as pairs of enantiomers [(a1 R , a2 R ), (a1 S , a2 S )], and each atropisomer is separable at room temperature. An alternate procedure for preparing 5 H -dibenzo[ b , d ]azepin-7(6 H )-ones involves the intramolecular Friedel-Crafts cyclization of N -benzyloxycarbonylated biaryl amino acids...

Macrophages employ an array of pattern recognition receptors to detect and eliminate intracellular pathogens that access the cytosol. The cytosolic carbohydrate sensors Galectin-3, -8, and -9 (Gal-3, Gal-8, and Gal-9) recognize damaged pathogen-containing phagosomes, and Gal-3 and Gal-8 are reported to restrict bacterial growth via autophagy in cultured cells. However, the contribution of these galectins to host resistance during bacterial infection in vivo remains unclear. We found that Gal-9 binds directly to Mycobacterium tuberculosis (Mtb) and Salmonella enterica serovar Typhimurium (Stm) and localizes to Mtb in macrophages...

With the emergence and success of checkpoint blockade immunotherapy, immuno-oncology has primarily focused on CD8 T cells, whose cytotoxic programs directly target tumor cells. However, the limited response rate of current immunotherapy regimens has prompted investigation into other types of tumor-infiltrating immune cells, such as CD4 T cells and B cells, and how they interact with CD8 T cells in a coordinated network. Recent studies have demonstrated the potential therapeutic benefits of CD4 T follicular helper (TFH) cells and B cells in cancer, highlighting the important role of their crosstalk and interactions with other immune cell components in the tumor microenvironment...

BACKGROUND: Modeling of single cell RNA-sequencing (scRNA-seq) data remains challenging due to a high percentage of zeros and data heterogeneity, so improved modeling has strong potential to benefit many downstream data analyses. The existing zero-inflated or over-dispersed models are based on aggregations at either the gene or the cell level. However, they typically lose accuracy due to a too crude aggregation at those two levels. RESULTS: We avoid the crude approximations entailed by such aggregation through proposing an independent Poisson distribution (IPD) particularly at each individual entry in the scRNA-seq data matrix...

BACKGROUND Anti-melanoma differentiation-associated protein 5-positive dermatomyositis (MDA5⁺ DM) is characterized by a life-threatening complication of rapidly progressive interstitial lung disease (RP-ILD). Early prediction of RP-ILD can enhance diagnostic accuracy and therapeutic efficacy. This study was conducted to develop a nomogram model for predicting RP-ILD in patients with MDA5⁺ DM. MATERIAL AND METHODS We retrospectively analyzed 53 patients with MDA5⁺ DM, of whom 21 patients were diagnosed with RP-ILD between January 2018 and January 2021...

Cellular senescence has been identified as a pathological mechanism linked to tau and amyloid beta (Aβ) accumulation in mouse models of Alzheimer's disease (AD). Clearance of senescent cells using the senolytic compounds dasatinib (D) and quercetin (Q) reduced neuropathological burden and improved clinically relevant outcomes in the mice. Herein, we conducted a vanguard open-label clinical trial of senolytic therapy for AD with the primary aim of evaluating central nervous system (CNS) penetrance, as well as exploratory data collection relevant to safety, feasibility, and efficacy...

INTRODUCTION: Evaluating differences in immune responses to Eimeria spp . between poultry genetic lines could be valuable for understanding favorable traits to address coccidiosis, a costly poultry disease. The objective was to compare peripheral blood mononuclear cell (PBMC) immunometabolism and composition during Eimeria challenge in three distinct and highly inbred genetic lines; Leghorn Ghs6, Leghorn Ghs13, and Fayoumi M5.1. METHODS: At hatch, 180 chicks (60/ line) were placed in wire-floor cages (10 chicks/cage) and fed a commercial diet...