Cell Adhesion System Research Articles

Degenerate Cahn–Hilliard systems: From nonlocal to local

We provide a rigorous mathematical framework to establish the limit of a nonlocal model of cell–cell adhesion system to a local model. When the parameter of the nonlocality goes to 0, the system tends to a Cahn–Hilliard system with degenerate mobility and cross-interaction forces. Our analysis relies on a-priori estimates and compactness properties.

Molecular pathological approach to cancer epigenomics and its clinical application.

Careful microscopic observation of histopathological specimens, accumulation of large numbers of high-quality tissue specimens, and analysis of molecular pathology in relation to morphological features are considered to yield realistic data on the nature of multistage carcinogenesis. Since the morphological hallmark of cancer is disruption of the normal histological structure maintained through cell-cell adhesiveness and cellular polarity, attempts have been made to investigate abnormalities of the cadherin-catenin cell adhesion system in human cancer cells. It has been shown that the CDH1 tumor suppressor gene encoding E-cadherin is silenced by DNA methylation, suggesting that a "double hit" involving DNA methylation and loss of heterozygosity leads to carcinogenesis. Therefore, in the 1990s, we focused on epigenomic mechanisms, which until then had not received much attention. In chronic hepatitis and liver cirrhosis associated with hepatitis virus infection, DNA methylation abnormalities were found to occur frequently, being one of the earliest indications that such abnormalities are present even in precancerous tissue. Aberrant expression and splicing of DNA methyltransferases, such as DNMT1 and DNMT3B, was found to underlie the mechanism of DNA methylation alterations in various organs. The CpG island methylator phenotype in renal cell carcinomawas identified for the first time, and its therapeutic targets were identified by multilayer omics analysis. Furthermore, the DNA methylation profile of nonalcoholic steatohepatitis (NASH)-related hepatocellular carcinomawas clarified in groundbreaking studies. Since then, we have developed diagnostic markers for carcinogenesis risk in NASH patients and noninvasive diagnostic markers for upper urinary tract cancer, as well as developing a new high-performance liquid chromatography-based diagnostic system for DNA methylation diagnosis. Research on the cancer epigenome has revealed that DNA methylation alterations occur from the precancerous stage as a result of exposure to carcinogenic factors such as inflammation, smoking, and viral infections, and continuously contribute to multistage carcinogenesis through aberrant expression of cancer-related genes and genomic instability. DNA methylation alterations at the precancerous stages are inherited by or strengthened in cancers themselves and determine the clinicopathological aggressiveness of cancers as well as patient outcome. DNA methylation alterations have applications as biomarkers, and are expected to contribute to diagnosis, as well as preventive and preemptive medicine.

Proteins in urine – Possible biomarkers of endometriosis

In the pathogenesis of endometriosis, a number of pathological reactions occur. Proteins secreted in the urine are thought to interact with each other and stimulate the pathological processes in endometriosis. Identifying one or more proteins that are specific enough and could serve as biomarkers for endometriosis is both a challenge and a necessity that would facilitate diagnosis. The urine of patients treated in a tertiary university hospital between July 1, 2020 and June 30, 2021 was analyzed. The studied group consists of patients who were treated surgically for endometriosis and in whom the diagnosis was confirmed by pathohistological analysis. The control group consists of patients who were operated for functional ovarian cysts. Urinary proteins were analyzed by chromatography and mass spectrometry (LC-MS/MS). We identified 17 proteins in urine whose concentrations were statistically significantly different in the group with endometriosis (N = 16) compared with the control groups (N = 16). The detected proteins were classified into groups according to their function in invasion, migration and proliferation, proteolysis, immune system, cell adhesion and vascular system. For all mentioned proteins the difference in concentration is statistically significant p < 0.005. Proteins are secreted in the urine of patients with endometriosis that may be involved in the pathogenesis of the disease and are possible biomarkers for endometriosis.

Proteomics profiling of vitreous humor reveals complement and coagulation components, adhesion factors, and neurodegeneration markers as discriminatory biomarkers of vitreoretinal eye diseases.

Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are leading causes of visual impairment and blindness in people aged 50 years or older in middle-income and industrialized countries. Anti-VEGF therapies have improved the management of neovascular AMD (nAMD) and proliferative DR (PDR), no treatment options exist for the highly prevalent dry form of AMD. To unravel the biological processes underlying these pathologies and to find new potential biomarkers, a label-free quantitative (LFQ) method was applied to analyze the vitreous proteome in PDR (n=4), AMD (n=4) compared to idiopathic epiretinal membranes (ERM) (n=4). Post-hoc tests revealed 96 proteins capable of differentiating among the different groups, whereas 118 proteins were found differentially regulated in PDR compared to ERM and 95 proteins in PDR compared to dry AMD. Pathway analysis indicates that mediators of complement, coagulation cascades and acute phase responses are enriched in PDR vitreous, whilst proteins highly correlated to the extracellular matrix (ECM) organization, platelet degranulation, lysosomal degradation, cell adhesion, and central nervous system development were found underexpressed. According to these results, 35 proteins were selected and monitored by MRM (multiple reaction monitoring) in a larger cohort of patients with ERM (n=21), DR/PDR (n=20), AMD (n=11), and retinal detachment (n=13). Of these, 26 proteins could differentiate between these vitreoretinal diseases. Based on Partial least squares discriminant and multivariate exploratory receiver operating characteristic (ROC) analyses, a panel of 15 discriminatory biomarkers was defined, which includes complement and coagulation components (complement C2 and prothrombin), acute-phase mediators (alpha-1-antichymotrypsin), adhesion molecules (e.g., myocilin, galectin-3-binding protein), ECM components (opticin), and neurodegeneration biomarkers (beta-amyloid, amyloid-like protein 2).

PSVIII-B-1 Biological Pathways Affecting Fertility in Dairy Cattle

Abstract Infertility is one of the most economically important traits for the dairy cattle industry, accounting for 22.1 % of culled cows in 2017. Therefore, the objectives of this study were to identify genomic regions via genome-wide association studies (GWAS) and to retrieve the biological pathways that are associated with variation in fertility traits in the dairy cow. Fertility records including days open (DO), Times Bred to Conception (TBRD), Calving Ease (CE), and Days in Milk (DIM) from the Cal Poly Dairy were collected from the DairyComp management system. After quality control, 345 individuals and about 782,000 SNPs were used in the GWAS analyses. Significant SNPs were mapped to the corresponding genes that were used for in-silico functional analyses using DAVID Software. A total of 3, 3, 8, 3, and 7 SNPs were significantly associated with chloride transmembrane transport, neutrophil chemotaxis, cell adhesion, starvation response and nervous system development. The functional analyses suggested potential molecular mechanisms such as chloride transmembrane transport (P = 0.017) and neutrophil chemotaxis (P = 0.02) as significant enriched biological pathways involved with variations seen for DO. Cell adhesion was found as a significant (P = 0.004) biological pathway for TBRD whereas the analysis revealed the starvation response mechanism as significant (P = 0.005) for CE. Nervous system development was significantly (P = 0.0003) associated with DIM. These results from the current study will be validated in a larger population with higher density panel and sequence data.

Super-resolved 3D-STED microscopy identifies a layer-specific increase in excitatory synapses in the hippocampal CA1 region of Neuroligin-3 KO mice

The chemical synapse is one type of cell-adhesion system that transmits information from a neuron to another neuron in the complex neuronal network in the brain. Synaptic transmission is the rate-limiting step during the information processing in the neuronal network and its plasticity is involved in cognitive functions. Thus, morphological and electrophysiological analyses of synapses are of particular importance in neuroscience research. In the current study, we applied super-resolved three-dimensional stimulated emission depletion (3D-STED) microscopy for the morphological analyses of synapses. This approach allowed us to estimate the precise number of excitatory and inhibitory synapses in the mouse hippocampal tissue. We discovered a region-specific increase in excitatory synapses in a model mouse of autism spectrum disorder, Neuroligin-3 KO, with this method. This type of analysis will open a new field in developmental neuroscience in the future.

Coping with brain amyloid: genetic heterogeneity and cognitive resilience to Alzheimer\u2019s pathophysiology

Although abnormal accumulation of amyloid in the brain is an early biomarker of Alzheimer’s disease (AD), wide variation in cognitive trajectories during life can be seen in the setting of brain amyloidosis, ranging from maintenance of normal function to progression to dementia. It is widely presumed that cognitive resilience (i.e., coping) to amyloidosis may be influenced by environmental, lifestyle, and inherited factors, but relatively little in specifics is known about this architecture. Here, we leveraged multimodal longitudinal data from a large, population-based sample of older adults to discover genetic factors associated with differential cognitive resilience to brain amyloidosis determined by positron emission tomography (PET). Among amyloid-PET positive older adults, the AD risk allele APOE ɛ4 was associated with worse longitudinal memory trajectories as expected, and was thus covaried in the main analyses. Through a genome-wide association study (GWAS), we uncovered a novel association with cognitive resilience on chromosome 8 at the MTMR7/CNOT7/ZDHHC2/VPS37A locus (p = 4.66 × 10–8, β = 0.23), and demonstrated replication in an independent cohort. Post-hoc analyses confirmed this association as specific to the setting of elevated amyloid burden and not explained by differences in tau deposition or cerebrovascular disease. Complementary gene-based analyses and publically available functional data suggested that the causative variant at this locus may tag CNOT7 (CCR4-NOT Transcription Complex Subunit 7), a gene linked to synaptic plasticity and hippocampal-dependent learning and memory. Pathways related to cell adhesion and immune system activation displayed enrichment of association in the GWAS. Our findings, resulting from a unique study design, support the hypothesis that genetic heterogeneity is one of the factors that explains differential cognitive resilience to brain amyloidosis. Further characterization of the underlying biological mechanisms influencing cognitive resilience may facilitate improved prognostic counseling, therapeutic application, and trial enrollment in AD.

Fibrinogen and Fibrin Differentially Regulate the Local Hydrodynamic Environment in Neutrophil–Tumor Cell–Endothelial Cell Adhesion System

As cancer is one of the major fatal diseases for human beings worldwide, the metastasis of tumor cells (TCs) from a blood vessel to an adjacent organ has become a focus of research. A tumor metastasis theory named the “two-step theory” pointed out that polymorphnuclear neutrophils (PMNs) could facilitate TC adhesion on an endothelial monolayer under flow, which was regulated by shear flow and promoted by fibrinogen and fibrin. In order to further understand the role of hydrodynamics played in the “two-step theory”, we improved our side-view micro-particle imaging velocimetry (PIV) system and successfully measured the flow velocity profiles around adherent PMNs and TCs on an endothelial monolayer in the presence of soluble fibrinogen or fibrin under shear flow. Combined with a computational fluid dynamics simulation, we found that: (1) soluble fibrinogen and fibrin influenced the variations of relative shear rates above an adhered PMN and an adherent TC at different PMN-to-TC position states; (2) compared with soluble fibrinogen, soluble fibrin made the curves of relative shear rates above an adherent cell flatter. Soluble fibrin might increase the collision frequency and affect the contact time and contact area between PMNs, TCs, and endothelium cells, resulting in the enhancement of TC adhesion and retention on an endothelial monolayer.

Olfactory Neuroepithelium Cells from Cannabis Users Display Alterations to the Cytoskeleton and to Markers of Adhesion, Proliferation and Apoptosis.

Cannabis is the third most commonly used psychoactive substance of abuse, yet it also receives considerable attention as a potential therapeutic drug. Therefore, it is essential to fully understand the actions of cannabis in the human brain. The olfactory neuroepithelium (ON) is a peripheral nervous tissue that represents an interesting surrogate model to study the effects of drugs in the brain, since it is closely related to the central nervous system, and sensory olfactory neurons are continually regenerated from populations of stem/progenitor cells that undergo neurogenesis throughout life. In this study, we used ON cells from chronic cannabis users and healthy control subjects to assess alterations in relevant cellular processes, and to identify changes in functional proteomic pathways due to cannabis consumption. The ON cells from cannabis users exhibited alterations in the expression of proteins that were related to the cytoskeleton, cell proliferation and cell death, as well as, changes in proteins implicated in cancer, gastrointestinal and neurodevelopmental pathologies. Subsequent studies showed cannabis provoked an increase in cell size and morphological alterations evident through β-Tubulin III staining, as well as, enhanced beta-actin expression and a decrease in the ability of ON cells to undergo cell attachment, suggesting abnormalities of the cytoskeleton and cell adhesion system. Furthermore, these cells proliferated more and underwent less cell death. Our results indicate that cannabis may alter key processes of the developing brain, some of which are similar to those reported in mental disorders like DiGeorge syndrome, schizophrenia and bipolar disorder.

Screening function enrichment and related signaling pathways bioinformatics analysis of differentially expressed gene in glioma

Objective: To screen the differentially expressed genes, functional enrichment and related signaling pathways in glioma by bioinformatics analysis. Methods: Microarray data of glioma related gene expression profiles were selected in GEO database, and differentially expressed genes in glioma patients and normal brain tissues were screened by R statistical software of lima package. Functional enrichment of differentially expressed genes (GO and KEGG) was performed. The protein-protein interaction database (STRING) was used to analyze the interaction between the screened differentially expressed genes and the related signaling pathways. Results: Two gene expression profiles, GSE15824 and GSE66354, were selected for analysis, and 158 genes with differential expression more than 2 times and P<0.05 were screened. Molecular function (MF) of 158 differentially expressed genes was integrin binding, cell adhesion molecule binding, calcium binding and AMPA glutamate receptor activity. Cell component localization (CC) was located in cell membrane, neuron cell body, axon of nerve cell and so on, while biological process (BP) was mainly cell adhesion and nervous system. Development, cell proliferation, GTPase activity, apoptosis and angiogenesis; KEGG signaling pathways were mainly cAMP signaling pathway, purine metabolism pathway, MAPK signaling pathway and cGMP-PKG signaling pathway. There were 177 interaction connections in 158 differential expression gene-protein interaction networks, with an average interaction of 2.39 between each node and an aggregation coefficient of 0.37. Cytohubb screened the key genes (hub genes) in the signaling pathway. The results indicated that SLC6A1,SLC1A2,BDNF,GAP43,NRXN1,GAD1,OLIG2, PLP1,S100B and GRIA3 were the key genes in the signaling pathway of the interacting protein network. All the 10 key genes were related to the prognosis of patients (P<0.05). Conclusions: There are differentially expressed genes profile in glioma tissues and normal tissues. SLC6A1, SLC1A2, BDNF, GAP43, NRXN1, GAD1, OLIG2, PLP1, S100B and GRIA3 are key genes for glioma development and are related to the prognosis of patients.

The Differentiation-Associated Keratinocyte Protein Cornifelin Contributes to Cell-Cell Adhesion of Epidermal and Mucosal Keratinocytes

Cornifelin (CNFN) has been identified as a protein component of epidermal corneocytes. Here, we investigated the tissue distribution of CNFN and potential consequences of CNFN deficiency on epithelial function in invitro models of human skin and oral mucosa. Our detailed bioinformatics and immunostaining analysis revealed that CNFN is not only expressed in human epidermis but also in noncornifying oral mucosa. In normal epidermis, CNFN was confined to the upper granular layer and the stratum corneum. By contrast, in both partly cornifying and noncornifying oral mucosa, CNFN was expressed in a cell membrane-associated pattern over several suprabasal layers. Small interfering RNA-mediated knockdown of CNFN in epidermal keratinocytes (KCs) was associated with only subtle alterations of the overall epidermal architecture in skin models invitro but led to altered morphology of corneodesmosomes, as detected by electron microscopy. Using dispase treatment followed by mechanical stress, epithelial sheets of CNFN-deficient epidermal KCs were easily disrupted, whereas their CNFN-competent counterparts remained intact. In contrast to the epidermal KCs, CNFN knockdown in oral KCs had a more severe effect and caused pronounced acantholysis in organotypic models of oral mucosa. Together, these findings indicate that CNFN is a structural component of the cell adhesion system of differentiated KCs in both epidermis and oral mucosa.

Basigin gene products associate to form a novel cell‐adhesion system used to maintain a metabolic cytoarchitecture and potentially stimulate an immune response in the neural retina

Two Basigin gene products are expressed in the vertebrate neural retina, named Basigin‐variant‐ 1 and Basigin‐variant‐2. Variant‐2 is found on cells throughout the body, including monocytes, as well as on the surface of Muller glial cells and retinal pigmented epithelial cells of the mammalian eye, whereas variant‐1 is considered a photoreceptor‐specific gene product. These membrane‐associated glycoproteins, which are members of the immunoglobulin (Ig) superfamily, are identical in amino acid sequence except for an additional Ig domain at the amino terminus of Basigin‐variant‐1. The amino acid sequence of the Basigin‐variant‐1‐specific Ig domain is well conserved throughout evolution, which suggests that it performs a conserved function. In addition, the Basigin‐variant‐1‐specific Ig domain is similar in amino acid sequence to a region of L1cam, a known Basigin‐variant‐2 binding partner in the brain. Therefore, the purpose of this study was to test the hypothesis that the Basigin‐variant‐1‐specific Ig domain binds to Basigin‐variant‐2. Recombinant forms of the Basigin‐variant‐1‐specific Ig domain and L1cam were generated via molecular techniques and used in enzyme‐linked immunosorbent assay (ELISA) binding assays with Basigin‐variant‐2 endogenously expressed in mouse neural retina and kidney, as well as the mouse monocytic cell line RAW 264.7. The results of the study indicate that the Basigin‐variant‐1‐specific Ig domain does bind Basigin‐variant‐2 with moderate affinity. The corresponding region of L1cam, however, does not interact with Basigin‐variant‐2, which suggests that amino acids within this highly conserved domain that are specific to Basigin‐variant‐ 1 but not L1cam are responsible for the interaction. The data suggest that Basigin‐variant‐1 does interact with Basigin‐variant‐2 to form a novel cell adhesion system between Müller cells and photoreceptors in the neural retina. The data also suggest that the same interaction can occur between Basigin‐variant‐1 on photoreceptor cells and Basigin‐variant‐2 on monocytes that invade the neural retina in response to a compromised retinal pigmented epithelium.Support or Funding InformationUNF Office of Academic AffairsThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Circular bead-like shapes of cell adhesion structures in 2D case

ABSTRACT Due to the strong deformation ability of cells, the cell adhesive stacking systems are more intricate than atom stacking systems. A general method to reveal their configurations still remains challenging. In this work a theoretic model is proposed to study the circular bead-like adhesion structures composed by equal cells in the two-dimensional (2D) case. Based on the free energy minimization theory, the equilibrium shape equations are obtained and analytical solutions are investigated for high symmetrical structures without volume constraints. All results are confirmed by the finite element method. These shapes are close to some bio-structures, such as the cross section of raspberry and orange. The symmetrical breaking is studied for high symmetrical structures with volume constraints and it reveals that there are abundant degenerated states in a cell adhesion system. These results are helpful for understanding the formation mechanism of the self-organizing cell adhesion structures.

Germ layer-specific regulation of cell polarity and adhesion gives insight into the evolution of mesoderm.

In triploblastic animals, Par-proteins regulate cell-polarity and adherens junctions of both ectodermal and endodermal epithelia. But, in embryos of the diploblastic cnidarian Nematostella vectensis, Par-proteins are degraded in all cells in the bifunctional gastrodermal epithelium. Using immunohistochemistry, CRISPR/Cas9 mutagenesis, and mRNA overexpression, we describe the functional association between Par-proteins, ß-catenin, and snail transcription factor genes in N. vectensis embryos. We demonstrate that the aPKC/Par complex regulates the localization of ß-catenin in the ectoderm by stabilizing its role in cell-adhesion, and that endomesodermal epithelial cells are organized by a different cell-adhesion system than overlying ectoderm. We also show that ectopic expression of snail genes, which are expressed in mesodermal derivatives in bilaterians, is sufficient to downregulate Par-proteins and translocate ß-catenin from the junctions to the cytoplasm in ectodermal cells. These data provide molecular insight into the evolution of epithelial structure and distinct cell behaviors in metazoan embryos.

Amyloid Fibrils with Positive Charge Enhance Retroviral Transduction in Mammalian Cells.

Amyloid fibrils are cross-β-sheet-rich protein/peptide fibrils that are typically associated with neurodegenerative diseases such as Parkinson's and Alzheimer's disease. Recently, functional amyloids have been discovered where amyloids are implicated in performing normal physiological functions of the host organism rather than creating diseases. The ability of amyloids to interact with the cell membrane and other small biomolecules exhibits its great potential to be used as a biomaterial for cell adhesion and gene delivery system. Given the established ability of semen-derived amyloids to concentrate HIV in semen and that of charged polymers as an enhancer of retroviral gene transfer, we hypothesized that charged amyloid fibrils can augment virus-mediated delivery system. We show that amyloids of α-synuclein formed in the presence and absence of cationic polymers chitosan and amyloid of poly-l-lysine can interact with lentiviral particles and enhance transduction efficiency in cells. The amyloid nanofibrils increase transduction efficiency up to ∼4 fold similar to widely used cationic polymer Polybrene. This study shows that amyloid nanofibril scaffolds may be used as targeted gene delivery systems.

Molecular Phenotyping of Telomerized Human Bone Marrow Skeletal Stem Cells Reveals a Genetic Program of Enhanced Proliferation and Maintenance of Differentiation Responses.

ABSTRACTLong‐term in vitro expansion of bone marrow stromal (skeletal) stem cells (also known as human mesenchymal stem cells [hMSC]) is associated with replicative senescence and impaired functions. We have previously reported that telomerization of hMSC through hTERT overexpression led to bypassing a replicative senescence phenotype and improved in vitro and in vivo functions. However, the molecular consequence of telomerization is poorly characterized. Thus, we compared the molecular phenotype of a well‐studied telomerized hMSC (hMSC‐TERT) cell line with primary hMSC. At a cellular level, both cell populations exhibited strong concordance for the known hMSC CD markers, similar responses to osteoblast (OB) differentiation induction, and formed heterotopic bone in vivo. Overall gene expression was highly correlated between both cell types with an average Pearson's correlation coefficient (R2) between the gene expression of all primary hMSC and all hMSC‐TERT samples of 0.95 (range 0.93–0.96). Quantitative analysis of gene expression of CD markers, OB cell markers, and transcription factors (TF) showed a high degree of similarity between the two cell populations (72%, 77%, and 81%, respectively). The hMSC‐TERT population was enriched mainly for genes associated with cell cycle and cell cycle signaling when compared with primary hMSC. Other enrichment was observed for genes involved in cell adhesion and skeletal system development and immune response pathways. Interestingly, hMSC‐TERT shared a telomerization signature with upregulation of cancer/testis antigens, MAGE, and PAGE genes. Our data demonstrate that the enhanced biological characteristics of hMSC after telomerization are mainly due to enhanced expression of cell proliferation genes, whereas gene expression responses to differentiation are maintained. © 2018 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research

Germ Layer Specific Regulation of Cell Polarity and Adhesion: Insight into the Evolution of Mesoderm

In triploblastic animals, Par proteins regulate cell-polarity and adherens junctions of both ectodermal and endodermal epithelia. But, in embryos of the diploblastic cnidarian Nematostella vectensis, Par proteins are eliminated altogether in the bifunctional endomesodermal epithelia. Using immunohistochemistry, CRISPR/Cas9, and overexpression of specific mRNAs, we describe the functional association between Par proteins, s- catenin, and snail genes in N. vectensis embryos. We demonstrate that the aPKC/Par complex regulates the localization of s-catenin in the ectoderm by directing its role in cell adhesion, and that endomesodermal epithelia are organized by a different cell adhesion system. We also show that snail genes, which are mesodermal markers in bilaterians, are sufficient to downregulate Par proteins and translocate s-catenin from the junctions to the cytoplasm in N. vectensis. These data provide insight into the evolution of epithelial structure and the evolution of mesoderm in metazoan embryos.

Mechanosensing and Mechanotransduction at Cell–Cell Junctions

Cell adhesion systems are defined by their ability to resist detachment force. Our understanding of the biology of cell-cell adhesions has recently been transformed by the realization that many of the forces that act on those adhesions are generated by the cells that they couple together; and that force at adhesive junctions can be sensed to regulate cell behavior. Here, we consider the mechanisms responsible for applying force to cell-cell junctions and the mechanosensory pathways that detect those forces. We focus on cadherins, as these are the best-studied examples to date, but it is likely that similar principles will apply to other molecular systems that can engage with force-generators within cells and physically couple those cells together.

Complex carbohydrate recognition by proteins: Fundamental insights from bacteriophage cell adhesion systems

Summary Protein–glycan interactions are ubiquitous in nature. Molecular description of complex formation and the underlying thermodynamics, however, are not well understood due to the lack of model systems. Bacteriophage tailspike proteins (TSP) possess binding sites for bacterial cell surfaces oligosaccharides. In this article we describe the analysis of TSP-oligosaccharide complexes. TSP provide large glycan interaction sites where affinity and specificity are guided by the protein surface solvation and the conformational space sampled by the respective glycan. Furthermore, we describe a computational approach to analyse the conformational space sampled by flexible glycans of bacterial origin, a prerequisite for a thorough understanding of TSP-oligosaccharide interactions.

A new insight into viral proteins as Immunomodulatory therapeutic agents: KSHV vOX2 a homolog of human CD200 as a potent anti-inflammatory protein.

The physiologic function of the immune system is defense against infectious microbes and internal tumour cells, Therefore, need to have precise modulatory mechanisms to maintain the body homeostasis. The mammalian cellular CD200 (OX2)/CD200R interaction is one of such modulatory mechanisms in which myeloid and lymphoid cells are regulated. CD200 and CD200R molecules are membrane proteins that their immunomodulatory effects are able to suppress inflammatory responses, particularly in the privilege sites such as CNS and eyes. Kaposi's sarcoma-associated herpesvirus (KSHV), encodes a wide variety of immunoregulatory proteins which play central roles in modulating inflammatory and anti-inflammatory responses in favour of virus dissemination. One such protein is a homologue of the, encoded by open reading frame (ORF) K14 and therefore called vOX2. Based on its gene expression profile during the KSHV life cycle, it is hypothesised that vOX2 modulates host inflammatory responses. Moreover, it seems that vOX2 involves in cell adhesion and modulates innate immunity and promotes Th2 immune responses. In this review the activities of mammalian CD200 and KSHV CD200 in cell adhesion and immune system modulation are reviewed in the context of potential therapeutic agents.