A Systematic Review and Meta-analysis of Iowa Oral Performance Instrument Measures in Persons with Parkinson's Disease Compared to Healthy Adults.

Measures of tongue strength and endurance using the Iowa Oral Performance Instrument (IOPI) may have diagnostic utility during clinical swallowing evaluations for persons with Parkinson's disease (PwPD). Thus, the objective was to systematically analyze the existing literature comparing IOPI values of tongue strength and endurance between age- and sex-match pairs of PwPD and healthy adults as well as across disease stages. A systematic review of 12 databases and Google Scholar identified five peer-reviewed articles published in English (1990-2019) that compared tongue strength and/or endurance between PwPD and controls.

The insertion sequence of the N2A region of titin exists in an extended structure with helical characteristics.

The giant sarcomere protein titin is the third filament in muscle and is integral to maintaining sarcomere integrity as well as contributing to both active and passive tension. Titin is a multi-domain protein that contains regions of repeated structural elements. The N2A region sits at the boundary between the proximal Ig region of titin that is extended under low force and the PEVK region that is extended under high force.

The major leukocyte chemotactic and activating factors in the mouse gut lumen are not N-formylpeptide receptor 1 agonists.

Cultured bacteria release N-formylpeptides, which are potent chemoattractants for phagocytic leukocytes acting at G-protein-coupled receptors FPR1 and FPR2. However, the distribution and immunologic activity of these molecules at mucosal surfaces, where large numbers of bacteria are separated from the immune system by epithelium, remain undefined. To investigate this for the gut, we tested leukocyte responses to cell-free gut luminal contents from C57Bl/6 mice fed a chow diet.

Characterization of Fpr-rs8, an atypical member of the mouse formyl peptide receptor gene family.

The formyl peptide receptor gene family encodes G protein-coupled receptors for phagocyte chemoattractants, including bacteria- and mitochondria-derived N-formylpeptides. The human family has 3 functional genes, whereas the mouse family has 7 functional genes and 2 possible pseudogenes (ΨFpr-rs2 and ΨFpr-rs3). Here we characterize ΨFpr-rs2, a duplication of Fpr-rs2.

CXCL12 signaling is independent of Jak2 and Jak3.

Janus kinases (Jaks) are a small family of cytoplasmic tyrosine kinases, critical for signaling by Type I and II cytokine receptors. The importance of Jaks in signaling by these receptors has been firmly established by analysis of mutant cell lines, the generation of Jak knock-out mice, and the identification of patients with Jak3 mutations. While a number of other ligands that do not bind Type I and II cytokine receptors have also been reported to activate Jaks, the requirement for Jaks in signaling by these receptors is less clear.

Redirecting migration of T cells to chemokine secreted from tumors by genetic modification with CXCR2.

T-cell-based immunotherapies provide a promising means of cancer treatment although durable antitumor responses are infrequent. A potential reason for these shortcomings may lie in the observed lack of trafficking of specific T cells to tumor. Our increasing knowledge of the process of trafficking involving adhesion molecules and chemokines affords us the opportunity to intervene and correct deficiencies in this process.

Amyloid-beta induces chemotaxis and oxidant stress by acting at formylpeptide receptor 2, a G protein-coupled receptor expressed in phagocytes and brain.

Amyloid-beta, the pathologic protein in Alzheimer's disease, induces chemotaxis and production of reactive oxygen species in phagocytic cells, but mechanisms have not been fully defined. Here we provide three lines of evidence that the phagocyte G protein-coupled receptor (N-formylpeptide receptor 2 (FPR2)) mediates these amyloid-beta-dependent functions in phagocytic cells. First, transfection of FPR2, but not related receptors, including the other known N-formylpeptide receptor FPR, reconstituted amyloid-beta-dependent chemotaxis and calcium flux in HEK 293 cells.

Amyloid (beta)42 activates a G-protein-coupled chemoattractant receptor, FPR-like-1.

Amyloid beta (Abeta) is a major contributor to the pathogenesis of Alzheimer's disease (AD). Although Abeta has been reported to be directly neurotoxic, it also causes indirect neuronal damage by activating mononuclear phagocytes (microglia) that accumulate in and around senile plaques. In this study, we show that the 42 amino acid form of beta amyloid peptide, Abeta(42), is a chemotactic agonist for a seven-transmembrane, G-protein-coupled receptor named FPR-Like-1 (FPRL1), which is expressed on human mononuclear phagocytes.

Selective CXCR4 antagonism by Tat: implications for in vivo expansion of coreceptor use by HIV-1.

Chemokines and chemokine receptors play important roles in HIV-1 infection and tropism. CCR5 is the major macrophage-tropic coreceptor for HIV-1 whereas CXC chemokine receptor 4 (CXCR4) serves the counterpart function for T cell-tropic viruses. An outstanding biological mystery is why only R5-HIV-1 is initially detected in new seroconvertors who are exposed to R5 and X4 viruses.

CCR8 on human thymocytes functions as a human immunodeficiency virus type 1 coreceptor.

To determine whether human immunodeficiency virus type 1 (HIV-1) coreceptors besides CXCR4 and CCR5 are involved in HIV-1 infection of the thymus, we focused on CCR8, a receptor for the chemokine I-309, because of its high expression in the thymus. Similar levels of CCR8 mRNA were detected in immature and mature primary human thymocytes. Consistent with this, [(125)I]I-309 was shown to bind specifically and with similar affinity to the surface of immature and mature human thymocytes.

Identification of a gammaherpesvirus selective chemokine binding protein that inhibits chemokine action.

Chemokines are involved in recruitment and activation of hematopoietic cells at sites of infection and inflammation. The M3 gene of gammaHV68, a gamma-2 herpesvirus that infects and establishes a lifelong latent infection and chronic vasculitis in mice, encodes an abundant secreted protein during productive infection. The M3 gene is located in a region of the genome that is transcribed during latency.

Gene cloning, RNA distribution, and functional expression of mCX3CR1, a mouse chemotactic receptor for the CX3C chemokine fractalkine.

Human fractalkine and its apparent murine counterpart neurotactin are the only members identified so far of the CX3C subfamily of chemokines. Recently, a human fractalkine receptor was identified and named CX3CR1. Here we have identified a mouse counterpart of this receptor.

Characterization of the signal transduction pathway activated in human monocytes and dendritic cells by MPIF-1, a specific ligand for CC chemokine receptor 1.

The receptor specificity and signal transduction pathway has been identified and characterized for a truncated form of myeloid progenitor inhibitory factor-1 (MPIF-1(24-99)). MPIF-1 binds specifically to sites, in particular CCR1, shared with macrophage inflammatory protein-1alpha (MIP-1alpha) on the surface of human monocytes and dendritic cells, as inferred by its ability to compete for [125I]MIP-1alpha, but not for [125I]MIP-1beta or [125I]monocyte chemotactic protein-1(MCP-1) binding to intact cells. Based on calcium flux, MPIF-1 is an agonist on CCR1-transfected HEK-293 cells, monocytes, and dendritic cells, but not on CCR5-, CCR8-, or CX3CR1-transfected cells.

CXCR4 and CCR5 on human thymocytes: biological function and role in HIV-1 infection.

Thymocyte infection with HIV-1 is associated with thymic involution and impaired thymopoiesis, particularly in pediatric patients. To define mechanisms of thymocyte infection, we examined human thymocytes for expression and function of CXCR4 and CCR5, the major cell entry coreceptors for T cell line-tropic (T-tropic) and macrophage-tropic (M-tropic) strains of HIV-1, respectively. CXCR4 was detected on the surface of all thymocytes.

Identification of CX3CR1. A chemotactic receptor for the human CX3C chemokine fractalkine and a fusion coreceptor for HIV-1.

Fractalkine is a multimodular human leukocyte chemoattractant protein and a member of the chemokine superfamily. Unlike other human chemokines, the chemokine domain of fractalkine has three amino acids between two conserved cysteines, referred to as the CX3C motif. Both plasma membrane-associated and shed forms of fractalkine have been identified.

CC chemokine receptors 1 and 3 are differentially regulated by IL-5 during maturation of eosinophilic HL-60 cells.

CC chemokine receptors 1 and 3 (CCR1 and CCR3) are expressed by eosinophils; however, factors regulating their expression and function have not previously been defined. Here we analyze chemokine receptor expression and function during eosinophil differentiation, using the eosinophilic cell line HL-60 clone 15 as a model system. RNA for CCR1, -3, -4, and -5 was not detectable in the parental cells, and the cells did not specifically bind CC chemokines.

Gene organization and promoter function for CC chemokine receptor 5 (CCR5).

CC chemokine receptor 5 (CCR5) functions physiologically as a receptor for the leukocyte chemoattractants macrophage inflammatory protein-1alpha, macrophage inflammatory protein-1beta, and RANTES, and functions pathologically as a key cell entry coreceptor for HIV-1. The factors that regulate CCR5 expression may be useful therapeutic targets for HIV-1 infection. To identify nuclear regulatory factors, we have located and functionally characterized the CCR5 gene promoter.

Identification of CCR8: a human monocyte and thymus receptor for the CC chemokine I-309.

The human CC chemokine I-309 is a potent monocyte chemoattractant and inhibits apoptosis in thymic cell lines. Here, we identify a specific human I-309 receptor, and name it CCR8 according to an accepted nomenclature system. The receptor has seven predicted transmembrane domains, is expressed constitutively in monocytes and thymus, and is encoded by a previously reported gene of previously unknown function named, alternatively, CY6, TER1, and CKR-L1.

Impaired host defense, hematopoiesis, granulomatous inflammation and type 1-type 2 cytokine balance in mice lacking CC chemokine receptor 1.

CC chemokine receptor 1 (CCR1) is expressed in neutrophils, monocytes, lymphocytes, and eosinophils, and binds the leukocyte chemoattractant and hematopoiesis regulator macrophage inflammatory protein (MIP)-1alpha, as well as several related CC chemokines. Four other CCR subtypes are known; their leukocyte and chemokine specificities overlap with, but are not identical to, CCR1, suggesting that CCR1 has both redundant and specific biologic roles. To test this, we have developed CCR1-deficient mice (-/-) by targeted gene disruption.

C3a and C5a are chemotaxins for human mast cells and act through distinct receptors via a pertussis toxin-sensitive signal transduction pathway.

Mast cells are known to accumulate at sites of inflammation, however, the chemotaxins involved are undefined. Since most natural leukocyte secretagogues also induce cell migration, and since the anaphylatoxins C3a and C5a are mast cell secretagogues, we hypothesized that both C3a and C5a are also mast cell chemotaxins. Here we report that C3a and C5a are, in fact, potent chemotaxins for the human mast cell line HMC-1.

Cloning and functional expression of CC CKR5, a human monocyte CC chemokine receptor selective for MIP-1(alpha), MIP-1(beta), and RANTES.

We have cloned a human cDNA for a novel CC chemokine receptor (CC CKR) designated CC CKR5 that has 48-75% amino acid identity to other CC CKRs. CC CKR5 mRNA was detected constitutively in primary adherent monocytes but not in primary neutrophils or eosinophils. Macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and RANTES were all potent agonists for CC CKR5 (EC50 = 3-30 nM) when calcium flux was measured in transfected HEK 293 cells, yet the apparent binding affinities of the corresponding iodinated chemokines to intact cells expressing the receptor were low (IC50 approximately 100 nM).

Enhanced expression of the eosinophil-derived neurotoxin ribonuclease (RNS2) gene requires interaction between the promoter and intron.

The eosinophil-derived neurotoxin (EDN/RNS2) is a member of the mammalian ribonuclease gene family and is one of four proteins found in the large specific granules of human eosinophilic leukocytes. The gene encoding EDN consists of two exons, including a noncoding exon 1, separated by a single intron from the coding sequence in exon 2. We have identified a functional promoter of the EDN gene and shown that optimal expression depends on interaction between the promoter and one or more sequence elements found in the single intron.

Molecular cloning of human eotaxin, an eosinophil-selective CC chemokine, and identification of a specific eosinophil eotaxin receptor, CC chemokine receptor 3.

The CC chemokine eotaxin is a selective chemoattractant for guinea pig eosinophils, first purified from bronchoalveolar lavage fluid in a guinea pig model of allergic airway inflammation. We have now isolated the gene and cDNA for a human counterpart of eotaxin. The gene maps to chromosome 17 and is expressed constitutively at high levels in small intestine and colon, and at lower levels in various other tissues.

Monocyte chemoattractant protein-3 is a functional ligand for CC chemokine receptors 1 and 2B.

The CC chemokine monocyte chemoattractant protein-3 (MCP-3) activates human monocytes, lymphocytes, basophils, and eosinophils. MCP-3 has been reported to induce [Ca2+]i changes in cells transfected with the monocyte-selective MCP-1 receptor 2B (CC CKR2B) and competes for 125I-MCP-1 binding on CC CKR2B, suggesting that it may mediate monocyte responses to MCP-3. However, we now show that MCP-3 is a ligand and potent agonist for the macrophage inflammatory protein-1 alpha (MIP-1 alpha)/regulated on activation, normal T expressed, and secreted protein (RANTES) receptor CC CKR1 (rank order for [Ca2+]i changes = MIP-1 alpha > MCP-3 > RANTES), which is expressed in monocytes > neutrophils > eosinophils.