Epithelial antimicrobial peptides in host defense against infection

One component of host defense at mucosal surfaces seems to be epithelium-derived antimicrobial peptides. Antimicrobial peptides are classified on the basis of their structure and amino acid motifs. Peptides of the defensin, cathelicidin, and histatin classes are found in humans. In the airways, α-defensins and the cathelicidin LL-37/hCAP-18 originate from neutrophils. β-Defensins and LL-37/hCAP-18 are produced by the respiratory epithelium and the alveolar macrophage and secreted into the airway surface fluid. Beside their direct antimicrobial function, antimicrobial peptides have multiple roles as mediators of inflammation with effects on epithelial and inflammatory cells, influencing such diverse processes as proliferation, immune induction, wound healing, cytokine release, chemotaxis, protease-antiprotease balance, and redox homeostasis. Further, antimicrobial peptides qualify as prototypes of innovative drugs that might be used as antibiotics, anti-lipopolysaccharide drugs, or modifiers of inflammation

Antimicrobial proteins and polypeptides in pulmonary innate defence

Inspired air contains a myriad of potential pathogens, pollutants and inflammatory stimuli. In the normal lung, these pathogens are rarely problematic. This is because the epithelial lining fluid in the lung is rich in many innate immunity proteins and peptides that provide a powerful anti-microbial screen. These defensive proteins have anti-bacterial, anti- viral and in some cases, even anti-fungal properties. Their antimicrobial effects are as diverse as inhibition of biofilm formation and prevention of viral replication. The innate immunity proteins and peptides also play key immunomodulatory roles. They are involved in many key processes such as opsonisation facilitating phagocytosis of bacteria and viruses by macrophages and monocytes. They act as important mediators in inflammatory pathways and are capable of binding bacterial endotoxins and CPG motifs. They can also influence expression of adhesion molecules as well as acting as powerful anti-oxidants and anti-proteases. Exciting new antimicrobial and immunomodulatory functions are being elucidated for existing proteins that were previously thought to be of lesser importance. The potential therapeutic applications of these proteins and peptides in combating infection and preventing inflammation are the subject of ongoing research that holds much promise for the future

Dendritic Cells Exposed to MVA-Based HIV-1 Vaccine Induce Highly Functional HIV-1-Specific CD8+ T Cell Responses in HIV-1-Infected Individuals

Currently, MVA virus vectors carrying HIV-1 genes are being developed as HIV-1/AIDS prophylactic/therapeutic vaccines. Nevertheless, little is known about the impact of these vectors on human dendritic cells (DC) and their capacity to present HIV-1 antigens to human HIV-specific T cells. This study aimed to characterize the interaction of MVA and MVA expressing the HIV-1 genes Env-Gag-Pol-Nef of clade B (referred to as MVA-B) in human monocyte-derived dendritic cells (MDDC) and the subsequent processes of HIV-1 antigen presentation and activation of memory HIV-1-specific T lymphocytes. For these purposes, we performed ex vivo assays with MDDC and autologous lymphocytes from asymptomatic HIV-infected patients. Infection of MDDC with MVA-B or MVA, at the optimal dose of 0.3 PFU/MDDC, induced by itself a moderate degree of maturation of MDDC, involving secretion of cytokines and chemokines (IL1-ra, IL-7, TNF-α, IL-6, IL-12, IL-15, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, IP-10, MIG, and IFN-α). MDDC infected with MVA or MVA-B and following a period of 48 h or 72 h of maturation were able to migrate toward CCL19 or CCL21 chemokine gradients. MVA-B infection induced apoptosis of the infected cells and the resulting apoptotic bodies were engulfed by the uninfected MDDC, which cross-presented HIV-1 antigens to autologous CD8+ T lymphocytes. MVA-B-infected MDDC co-cultured with autologous T lymphocytes induced a highly functional HIV-specific CD8+ T cell response including proliferation, secretion of IFN-γ, IL-2, TNF-α, MIP-1β, MIP-1α, RANTES and IL-6, and strong cytotoxic activity against autologous HIV-1-infected CD4+ T lymphocytes. These results evidence the adjuvant role of the vector itself (MVA) and support the clinical development of prophylactic and therapeutic anti-HIV vaccines based on MVA-B

MODELING THE DYNAMICS OF FOREST ECOSYSTEMS TAKING INTO ACCOUNT THEIR STRUCTURAL HETEROGENEITY AT DIFFERENT FUNCTIONAL AND SPATIAL LEVELS

In many problems of modern forest ecology, it is necessary to analyze the conjugated dynamics of processes occurring at different spatio-temporal scales of the functioning of plant communities and soils resulted from their interaction under the influence of all edaphic and anthropogenic factors. Mathematical models can be an efficient tool for such analysis. The aim of this study is to present the implementation of a new system of models that makes it possible to reproduce in simulation experiments the spatial structure of forest phytocenoses formed by tree and grass-shrub layers, as well as associated heterogeneity of soil conditions and the diversity of ecological niches at different hierarchical levels. To determine the required level of detail of the spatial heterogeneity of forest biogeocenoses related to the processes of their multi-scale functioning, experimental studies were carried out on permanent sampling plots in the Prioksko-Terrasny State Natural Biosphere Reserve and in the “Kaluzhskie Zaseki” State Nature Reserve. The spatial structure of communities and related heterogeneity of ecological conditions were studied using traditional soil and geobotanical, as well as modern instrumental methods. The obtained data were used to construct the algorithms and to estimate the parameters of different blocks of the new system of models. The implementation of a spatially-explicit process-based system of models has shown its ability to reproduce the dynamics of forest ecosystems, taking into account the species composition and spatial structure of different layers of vegetation and the associated patchiness of soil conditions. Because of a wide range of interrelated ecosystem characteristics implemented in the system of models it is possible to simulate productivity, biological turnover of C and N, and the dynamics of forest ecosystems, taking into account their characteristic spatial structure at different scales. This makes it possible to improve the understanding of ecosystem processes and their contribution to maintaining the sustainable functioning of forests, which can be used for predictive assessments of the efficiency of forest management techniques and in solving other forestry and environmental problems

Preparation of the Low Molecular Weight Serum Proteome for Mass Spectrometry Analysis.

The ability to cure or manage many diseases is highly dependent on the ability to correctly diagnose them at the earliest possible stage. Diagnosis relies heavily on biomarkers whether these be visual symptoms or molecules found within samples acquired from the patient. For conditions that lack useful biomarkers, researchers are often faced with the task of sifting through very complex biological samples (i.e., serum, plasma, urine, tissue, cells, etc.) with the hope of discovering a small number of molecules that are exquisitely diagnostic for the condition of interest. One discovery strategy that has been frequently used is to fractionate the biological samples being studied into simpler aliquots that can be more easily characterized using existing technologies. One such fractionation method is to isolate a specific portion based on a specific property (i.e., size, phosphorylation state, charge, etc.) of the proteins within the sample. This method provides a simplified sample that can be characterized at a higher coverage level than the complex sample from which it was derived. This chapter details one of these methods, the extraction and analysis of the low molecular weight proteome of human serum