A targeted GC-MS/MS approach for the determination of eight sterols in microgreen and mature plant material.

Over the past decades, a remarkable number of scientific studies supported the correlation between an adequate dietary intake of phytosterols (PS) and the reduced risk of cardiovascular diseases. PS are known to inhibit the intestinal absorption of cholesterol, thus promoting the reduction of the low-density lipoproteins (LDL) amount in the bloodstream. Despite the fact that a non-negligible atherogenicity was recognized to PS, thus requiring a careful risk-benefits assessment for plant sterol supplementation, the potential role of PS as cholesterol-lowering agents has been contributing to the spreading awareness of the health benefits associated with the consumption of plant-based foods. In recent years, this has been fueling the market of innovative vegetable products, such as microgreens. Surprisingly, the recent literature concerning microgreens exhibited the lack of studies focusing on the characterization of PS. To fill this gap, a validated analytical method based on the hyphenation of gas chromatography and tandem mass spectrometry is proposed here for the quantitative analysis of eight phytosterols, namely ß-sitosterol, campesterol, stigmasterol, brassicasterol, isofucosterol, and cholesterol, lathosterol and lanosterol. The method was exploited for the characterization of the PS content in 10 microgreen crops, i.e., chia, flax, soybean, sunflower, rapeseed, garden cress, catalogna chicory, endive, kale and broccoli raab. Finally, these results were compared to the PS content of mature forms of kale and broccoli raab. A remarkable amount of PS was detected in chia, flax, rapeseed, garden cress, kale, and broccoli raab microgreens. 100 g (wet weight) of these microgreen crops were found to contain from 20 to 30 mg of the investigated PS. Interestingly, in the case of kale and broccoli raab microgreens, the overall PS content was higher than the one measured in the edible parts of the corresponding mature forms. Additionally, a symmetric change of the PS inner profile was observed between the two growth stages of the latter two crops. Here, the overall decrease of the PS sterol content in the mature forms was associated with the increase of the relative amount of ß-sitosterol and campesterol at the expense of minor PS species, such as brassicasterol.

Wine yeast selection in the Iberian Peninsula: Saccharomyces and non-Saccharomyces as drivers of innovation in Spanish and Portuguese wine industries.

Yeast selection for the wine industry in Spain started in 1950 for the understanding of the microbial ecology, and for the selection of optimal strains to improve the performance of alcoholic fermentation and the overall wine quality. This process has been strongly developed over the last 30 years, firstly on Saccharomyces cerevisiae, and, lately, with intense activity on non-Saccharomyces. Several thousand yeast strains have been isolated, identified and tested to select those with better performance and/or specific technological properties. The present review proposes a global survey of this massive ex-situ preservation of eukaryotic microorganisms, a reservoir of biotechnological solutions for the wine sector, overviewing relevant screenings that led to the selection of strains from 12 genera and 22 species of oenological significance. In the first part, the attention goes to the selection programmes related to relevant wine-producing areas (i.e. Douro, Extremadura, Galicia, La Mancha and Uclés, Ribera del Duero, Rioja, Sherry area, and Valencia). In the second part, the focus shifted on specific non-Saccharomyces genera/species selected from different Spanish and Portuguese regions, exploited to enhance particular attributes of the wines. A fil rouge of the dissertation is the design of tailored biotechnological solutions for wines typical of given geographic areas.

Health-related quality of life among intensive care unit workers.

OBJECTIVE: To analyse health-related quality of life in a sample of doctors and nurses from 2 intensive care units in the city of Buenos Aires, Argentina. METHODS: An analytical, cross-sectional and quantitative study. The Spanish version of the SF-36 questionnaire was used, which comprises 8 dimensions grouped into 2 components (physical and mental) and evaluates the health status of respondents on a scale from 0 to 100; the higher the score, the better the perception of health status. RESULTS: Ninety-five professionals from 2 intensive care units participated, 58% from a private institution and the rest from a public institution. The majority were women (57%), doctors (37%) with an average age of 42 years and with a maximum undergraduate degree and degree (59%). Of the dimensions making up health-related quality of life, the vitality dimension was perceived poorest with an average of 53.3, and physical function was the best evaluated at 87.8. The physical component dimensions were better evaluated than those of the mental component. The variables sex (male), age (> 40 years), presence of chronic diseases, qualification (medical), hourly workload (> 40 h per week) and years of service (> 11 years), seem to have a negative influence on the perception of health-related quality of life. CONCLUSIONS: Strategies need to be implemented to reduce the impact of work activity on the mental and physical health of health professionals. Strategies for health promotion and the prevention of known psychosocial and ergonomic risks are required, and workloads and duration of working hours need to be adjusted to preserve the integrity of health workers.

Health-related quality of life among intensive care unit workers. / Calidad de vida relacionada con la salud en trabajadores de unidades de cuidados intensivos.

OBJECTIVE: To analyse health-related quality of life in a sample of doctors and nurses from 2 intensive care units in the city of Buenos Aires, Argentina. METHOD: An analytical, cross-sectional and quantitative study. The Spanish version of the SF-36 questionnaire was used, which comprises 8 dimensions grouped into 2 components (physical and mental) and evaluates the health status of respondents on a scale from 0 to 100; the higher the score, the better the perception of health status. RESULTS: Ninety-five professionals from 2 intensive care units participated, 58% from a private institution and the rest from a public institution. The majority were women (57%), doctors (37%) with an average age of 42 years and with a maximum undergraduate degree and degree (59%). Of the dimensions making up health-related quality of life, the vitality dimension was perceived poorest with an average of 53.3, and physical function was the best evaluated at 87.8. The physical component dimensions were better evaluated than those of the mental component. The variables sex (male), age (>40 years), presence of chronic diseases, qualification (medical), hourly workload (>40h per week) and years of service (>11 years), seem to have a negative influence on the perception of health-related quality of life. CONCLUSIONS: Strategies need to be implemented to reduce the impact of work activity on the mental and physical health of health professionals. Strategies for health promotion and the prevention of known psychosocial and ergonomic risks are required, and workloads and duration of working hours need to be adjusted to preserve the integrity of health workers.

Wine aromatic compound production and fermentative behaviour within different non-Saccharomyces species and clones.

AIMS: Twenty-five enological yeasts belonging to nine different species (Candida zeylanoides, Cryptococcus uzbekistanensis, Debaryomyces hansenii, Lachancea thermotolerans, Metschnikowia pulcherrima, Torulaspora delbrueckii, Williopsis pratensis, Zygosaccharomyces bailii and Saccharomyces cerevisiae) were screened for aroma formation and fermentative behaviour as part of a non-Saccharomyces yeast selection programme. METHODS AND RESULTS: Pure cultures were inoculated in pasteurized grape juice in order to perform alcoholic fermentations. Some non-Saccharomyces species did not ferment, others did not get established and none of them completed alcoholic fermentations. The physico-chemical parameters of the wines and the abundance of aromatic compounds at the end of alcoholic fermentation highlighted the notable differences in the aroma-forming ability and fermentative behaviour of the different non-Saccharomyces species, but not within clones. CONCLUSIONS: Lower diversity was detected within non-Saccharomyces species than that reported in S. cerevisiae with regard to enological behaviour and aromatic profiles. Metschnikowia pulcherrima and L. thermotolerans are the two species with higher possibilities to become an inoculum. SIGNIFICANCE AND IMPACT OF THE STUDY: Few significant differences were found within clones of the same species, but very important parameters in wine quality, such as volatile acidity, ethyl acetate and acetoin, which would justify selection programmes within those species. The results also demonstrated that T. delbrueckii and L. thermotolerans are two close species in their aromatic profiles.

Effects on grape amino acid concentration through foliar application of three different elicitors.

Elicitors play an important role in the defense against pathogens as an alternative to chemical pesticides by increasing secondary metabolites. Their effect on grape amino acid has been little investigated. Thus, the aim of this research was to study the influence of methyl jasmonate (MeJ), chitosan (CHT), and a yeast extract (YE) on grape amino acid composition, through foliar applications to grapevines. The must amino acid concentration was analyzed by HPLC. The results showed that CHT and YE treatments decreased the must concentration of several amino acids, affecting total amino acid content (from 2364 to 1961, and 1818mg/L, respectively). However, MeJ treatment had a slight effect on grape amino acid content, increasing the concentration of Met (from 8.95 to 12.13mg/L) and Phe (from 7.96 to 9.29mg/L). It seems to be that, the resistance induction through CHT and YE treatments results in physiological costs to grapevines associated with a decrease on grape amino acid concentration. Consequently, MeJ applications, as a viticultural practice, could be a better tool than CHT and YE treatments, because did not affect grape amino acid concentration.

Grafting response to excess boron and expression analysis of genes coding boron transporters in tomato.

Boron (B) is essential for plant growth, however its excess in soil and/or in irrigation water can severely compromise plant growth and yield. The goal of this work was to determine whether grafting onto 'Arnold', a commercial interspecific hybrid (Solanum lycopersicum × S. habrochaites) rootstock, which in a previous study was found to be tolerant to salt stress, could improve tomato (S. lycopersicum L. 'Ikram') tolerance to excess B, and whether this effect is associated with an exclusion mechanism. Non-grafted, self-grafted and grafted plants were hydroponically grown in a greenhouse with B concentration in the nutrient solution of 0.27 (control), 5, 10 and 15 mg·l-1 . A transcription analysis was carried out on SlNIP5 and SlBOR1 genes, which encode putative B transporters. Grafting 'Ikram' onto 'Arnold' rootstock reduced B concentration in leaf tissue of plants exposed to B concentrations of 10-15 mg·l-1 . At high B levels, SlNIP5 was down-regulated in all grafting combinations, while SlBOR1 was down-regulated only in the roots of plants grafted onto 'Arnold'. We conclude that grafting the susceptible tomato cultivar 'Ikram' onto the commercial rootstock 'Arnold' improved tolerance to excess B by reducing expression of genes encoding for B transporters at the root level, thus partially reducing the root uptake of B and its accumulation in the shoot.

Genetic and phenotypic intraspecific variability of non-Saccharomyces yeasts populations from La Rioja winegrowing region (Spain).

AIMS: To determine the intraspecific genetic diversity within five non-Saccharomyces yeast species and the diversity in phenotypic characteristic related to their technological properties. METHODS AND RESULTS: Seventy-one non-Saccharomyces yeasts isolated from different fermentations and facilities of the DOCa Rioja (Spain) belonging to five different wine species (Torulaspora delbrueckii, Lachancea thermotolerans, Metschnikowia pulcherrima, Zygosaccharomyces bailii and Williopsis pratensis) were subjected to clonal characterization by RAPD-PCR, which evidenced wide diversity between them. They were also submitted to a screening for some oenological traits related to the improvement of the aroma of the wine and yeast development in musts. Strains within the same species showed different enzyme activities, tolerated different levels of SO2 and possessed different killer phenotypes. These characteristics made them adjust better or worse to specific vinification processes or wine quality criteria. CONCLUSIONS: A significant genetic and phenotypic variation within the non-Saccharomyces species studied was found, which makes necessary to carry out a selection process in each one. SIGNIFICANCE AND IMPACT OF THE STUDY: Williopsis pratensis, a species that has not been thoroughly explored, may deserve further consideration for oenological applications. Due to the wide range of variation within species, the strains adaptation to the SO2 levels in musts has to be taken into account in selection processes.

Phenylalanine and urea foliar applications to grapevine: effect on wine phenolic content.

Phenolic compounds play a key role in the organoleptic properties of wines. Viticultural practices may influence grape and wine phenolic content, thus determining their quality. The objective of this study was to evaluate the effect of foliar applications of phenylalanine and urea, at two different doses, on wine phenolic composition. Grapes were harvested at their optimal technological maturity and their respective wines were elaborated at small scale. Wine detailed phenolic composition was determined. Results revealed that the content of several anthocyanins and flavonols was enhanced by the application of both phenylalanine doses and by the application of the low dose of urea. In contrast, flavanols and non-flavonoid compounds were less affected by the foliar treatments. The findings seem to be related to the time of application, since anthocyanins and flavonols are accumulated after veraison. In conclusion, nitrogen foliar fertilization increased the phenolic content of Tempranillo wines. This could be of interest since anthocyanins and flavonols are associated with wine quality, especially with its color.

Generation of ß cell-specific human cytotoxic T cells by lentiviral transduction and their survival in immunodeficient human leucocyte antigen-transgenic mice.

Several ß cell antigens recognized by T cells in the non-obese diabetic (NOD) mouse model of type 1 diabetes (T1D) are also T cell targets in the human disease. While numerous antigen-specific therapies prevent diabetes in NOD mice, successful translation of rodent findings to patients has been difficult. A human leucocyte antigen (HLA)-transgenic mouse model incorporating human ß cell-specific T cells might provide a better platform for evaluating antigen-specific therapies. The ability to study such T cells is limited by their low frequency in peripheral blood and the difficulty in obtaining islet-infiltrating T cells from patients. We have worked to overcome this limitation by using lentiviral transduction to 'reprogram' primary human CD8 T cells to express three T cell receptors (TCRs) specific for a peptide derived from the ß cell antigen islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP265-273 ) and recognized in the context of the human class I major histocompatibility complex (MHC) molecule HLA-A2. The TCRs bound peptide/MHC multimers with a range of avidities, but all bound with at least 10-fold lower avidity than the anti-viral TCR used for comparison. One exhibited antigenic recognition promiscuity. The ß cell-specific human CD8 T cells generated by lentiviral transduction with one of the TCRs released interferon (IFN)-γ in response to antigen and exhibited cytotoxic activity against peptide-pulsed target cells. The cells engrafted in HLA-A2-transgenic NOD-scid IL2rγ(null) mice and could be detected in the blood, spleen and pancreas up to 5 weeks post-transfer, suggesting the utility of this approach for the evaluation of T cell-modulatory therapies for T1D and other T cell-mediated autoimmune diseases.

Study of the effects of proline, phenylalanine, and urea foliar application to Tempranillo vineyards on grape amino acid content. Comparison with commercial nitrogen fertilisers.

The aim of this work was to study the influence of foliar application of different nitrogen sources on grape amino acid content. The nitrogen sources applied to Tempranillo grapevines were proline, phenylalanine, urea, and two commercial nitrogen fertilisers, both without and with amino acids in their formulations. All treatments were applied at veraison and one week later. Proline treatment did not affect the must nitrogen composition. However, phenylalanine and urea foliar application enhanced the plants' synthesis of most of the amino acids, producing similar effects. In addition, the spray of commercial nitrogen fertilisers over leaves also induced a rise in grape amino acid concentrations regardless of the presence or absence of amino acids in their formulation. The most effective treatments were phenylalanine and urea followed by nitrogen fertilisers. This finding is of oenological interest for improved must nitrogen composition, ensuring better fermentation kinetics and most likely enhancing wine quality.

Comparison of culture media for the recovery of airborne yeast in wineries.

The direct air sampling impaction method on agar was evaluated using aerobiocollectors for the recovery of yeasts present in the winery air. Three culture media with different composition and specificity were studied. In addition, a resuscitation phase was included before the culture in the specificity medium [in the case of the Dekkera-Brettanomyces Differential Medium (DBDM) medium]. Sampling was conducted at different times of the year and in different parts of the wineries, which were different in age and design. Both the Chloramphenicol Glucose Agar (CGA) and Agar Lysine AL media recovered yeasts from the air without any prior resuscitation phase. CGA was able to recover a higher number of colony-forming units of yeasts than the other media. Consequently, to estimate the number of yeasts present in winery air, the best choice of medium would be CGA. The AL medium permitted the growth of the greatest range of genera and species. If the aim is to study the diversity of yeasts present in the air, the most suitable medium is AL. Neither CGA nor AL proved suitable for recovering yeasts of the Brettanomyces genus. The DBDM medium was the only one which provided sufficient specificity for their recovery and identification from the air, although their special characteristics made a prior protocol of resuscitation necessary.

Factors of influence in the distribution of mold in the air in a wine cellar.

UNLABELLED: This paper studies the presence of mold in the air of a vinification and ageing wine cellar. The influence of other factors such as the time of year, the sampling point, and the activity being carried out in the cellar has been analyzed. Neither the type of activity being carried out in the cellar nor the temperature or relative humidity fluctuations throughout the year are determining factors in the presence of mold in the air. For this group of microorganisms, the design of the cellar studied is the fundamental factor. Areas with little ventilation favor high levels of relative humidity and, hence, a higher presence of mold in the air. The mold population in these areas is not very diverse, which indicates that colonization by certain types of mold that have adapted to the conditions established therein is permanent. Areas with greater air flow, constant activity, and frequent cleaning show lower mold populations in the air and of a more varied composition. PRACTICAL APPLICATION: This work shows that given the growing importance of the presence of mold in wine cellars, the design thereof should take into account suitable ventilation of all the areas and control of the relative humidity. Hence, the presence of traditional underground areas for ageing wine, which is justifiable in seasons where temperature and humidity control lead to major technical problems, should be reconsidered in the design of new wine cellars.

Presence of non-Saccharomyces yeasts in cellar equipment and grape juice during harvest time.

The purpose of this study was to analyze the presence of different yeasts in the facilities of four wineries from the D.O.Ca. Rioja region in Spain. The study was conducted through the identification of the yeasts via the PCR-RFLP technique of the ITS region of rDNA. The diversity of non-Saccharomyces yeasts found in wineries has previously only been studied to a limited extent, despite the fact that these yeasts take part both in the start of spontaneous fermentation and in the changes which occur in the wines during their subsequent conservation. Most earlier studies carried out on cellar ecosystems have focussed on the clonal diversity of Saccharomyces cerevisiae. The results obtained in this study indicated that the presence of non-Saccharomyces yeasts in facilities is higher than that of the S. cerevisiae, with percentages of over 60% in all the wineries analyzed. Yeasts belonging to 10 genera and 18 species were isolated, but the only genera present in all four wineries were Cryptococcus, Pichia, and Saccharomyces. The Zygosaccharomyces bailii yeast responsible for taint was detected in one cleaned winery, in both the winemaking equipment and the fermenting must. It was also noted that the quantity and type of yeasts present in the facilities are related to the product used for cleaning them. It is also necessary to point out that the cleaning of the cellars prior to the reception of the grapes does not completely eliminate the yeasts present, so that these can subsequently become part of the vinification process.

Presence of lactic bacteria in the air of a winery during the vinification period.

In this paper we have studied the presence and evolution in the winery air of the lactic bacteria responsible for malolactic fermentation. Sampling took place during the winemaking process (between September 2007 and July 2008) in a winery from the Rioja appellation in Spain. The results obtained indicated that the presence of these microorganisms in the atmosphere was detected when grapes were entering the winery, while malolactic fermentation was taking place, and when liquid containing bacteria was manipulated. The species and clones of the lactic bacteria identified were also related to those present in the vinification tanks at any given stage of the process.

The target cell response to cytokines governs the autoreactive T cell repertoire in the pancreas of NOD mice.

AIMS/HYPOTHESIS: The pancreatic beta cell response to cytokines is crucial for the development of type 1 diabetes in the NOD mouse. For example, beta cell production of suppressor of cytokine signalling-1 (SOCS-1) protects against diabetes. This finding and other recent studies indicated that cytokine-stressed beta cells might contribute to disease progression by affecting the pancreatic lymphocyte infiltrate. The aim of this study was to provide insight into how the beta cell influences the pancreas-infiltrating T cell repertoire. METHODS: Lymphocytes isolated from Socs1-transgenic (tg) and non-tg NOD mice were analysed by flow cytometry. mRNA and protein levels in pancreatic islets were measured by real-time PCR and immunofluorescence analysis, respectively. RESULTS: The percentages of regulatory T cells, total counts and ratios between infiltrating CD8+ and CD4+ T cells, and the expression of killer cell lectin-like receptor subfamily K, member 1 (NKG2D) on CD8+ T cells did not differ in pancreases from prediabetic Socs1-tg and non-tg NOD mice. However, a striking difference in the percentages of CD8+ T cells specific for glucose 6-phosphatase catalytic subunit-related protein 206-214 was found, showing that SOCS-1 prevents the accumulation of high percentages of self-reactive CD8+ T cells in the pancreas. It was also found that protection from diabetes in Socs1-tg NOD mice correlated with a reduced expression of Cxcl10 mRNA in IFN-gamma treated islets. CONCLUSIONS/INTERPRETATION: This study highlights an important role for the beta cell in the local regulation of the diabetogenic process. By responding to the pro-inflammatory pancreas milieu it strongly influences the islet-reactive T cell repertoire in the pancreas.

Effect of the addition of inert cellulose substrates to grape must on Saccharomyces cerevisiae diversity and the evolution of alcoholic fermentation.

AIMS: To study the addition of cellulose-based adjuvant as a resource to offset the negative effects produced by grape juice clarification during alcoholic fermentations. METHODS AND RESULTS: The effect of the addition of two kinds of inert cellulose substrates in white wine vinification was investigated in two different musts. In one of these musts, stuck fermentations were detected. One of the types of cellulose examined had a fining effect, which caused a decrease in the number of viable yeasts in the medium and altered the distribution and frequency of the clones, which performed the fermentation. The other cellulose substrate made the medium cloudier but did not alter the distribution of yeasts in comparison with the control. CONCLUSIONS: The behaviour of the inert cellulose substrates on vinification depends on its physical characteristics and its capacity for making the must cloudy. SIGNIFICANCE AND IMPACT OF THE STUDY: The addition of inert cellulose substrates in white wine vinification improves the fermentation process and the quality of wines obtained. This effect is more noticeable in difficult fermentations. One variety of cellulose showed an inhibitory effect on Torulaspora delbrueckii yeasts.

Dissecting autoimmune diabetes through genetic manipulation of non-obese diabetic mice.

Type 1 diabetes results from a genetically and immunologically complex autoimmune process that is specifically directed against the pancreatic beta cells. Non-obese diabetic mice spontaneously develop a form of autoimmune diabetes closely resembling the disease in humans. This happens because, like human diabetic patients, non-obese diabetic mice have an unfortunate combination of apparently normal alleles at numerous loci associated with Type 1 diabetes. In isolation, each of these allelic variants affords a small degree of susceptibility to diabetes. In combination, however, they set in motion a series of immunological events that lead to islet inflammation and overt diabetes. Type 1 diabetes is associated with defects in self-tolerance and immunoregulation. It involves presentation of beta cell antigens to autoreactive T lymphocytes by professional antigen-presenting cells, the recruitment of antigen-activated T cells into pancreatic islets, and the differentiation of these antigen-activated lymphocytes into beta cell killers. Understanding the precise sequence of events in the pathogenesis of Type 1 diabetes has been, and remains, a challenging task. Much of our understanding of the immunology of the disease stems from studies of genetically engineered, non-obese diabetic mice. These mice provide reductionist systems, with which the contribution of individual cellular elements, molecules or genes to the disease process can be dissected. This review focuses on the lessons that have been learned through studies of these mice.

[Childhood cancer in the Autonomous Community of Cantabria in Spain (1995-2000)]. / Cáncer infantil en la comunidad de Cantabria (1995-2000).

BACKGROUND: Since 1980, the epidemiology of childhood cancer in Spain has been registered through the National Registry of Childhood Cancer. However, this registry does not include patients from Autonomous Community of Cantabria because there is no reporting clinical center. The absence of data on childhood cancer in this region justifies this study. OBJECTIVES: To analyze the clinical presentation, diagnostic delay and incidence of childhood cancer in Cantabria. METHODS: We performed a retrospective analysis of 89 children (aged 0-15 years) diagnosed with cancer in Cantabria from 1995-2000. RESULTS: The annual incidence of childhood cancer in the region was 198.1 cases per million inhabitants with a predominance of males (53.9 %) and children aged less than 5 years (46.1 %). The most frequent cancers were leukemia (32.6 %) and brain tumors (23.6 %). The most frequent signs and symptoms were fever (29.2 %) and decreased appetite or fatigue (19.1 %). The mean delay in diagnosis for all tumors was 5.99 weeks and delays were longest for brain tumors. There was a direct statistical relationship between non-specific clinical presentation and diagnostic delay. A total of 20.2 % of all patients received treatment outside Cantabria. CONCLUSIONS: The incidence of all childhood cancers and especially that of neuroblastoma was higher in Cantabria than in other areas of Spain. In general, the major difficulties in the diagnosis of childhood cancer are its low incidence and non-specific presenting symptoms. Specialized pediatric oncology units near to patients' homes should be created to avoid problems due to treatment outside the area of residence.

Effector lymphocytes in autoimmunity.

Autoimmune diseases result from complex interactions among different T- and B-lymphocyte subpopulations that target a rapidly growing number of autoantigens on different cell types. The etiology of most spontaneous autoimmune disorders, and both the kinetics and hierarchy of the underlying autoimmune responses are poorly understood. However, important advances have been made in recent years in our understanding of how autoreactive lymphocytes cause tissue damage, including the discovery that granzyme B binds to a cell surface receptor on target cells. This review is an attempt to summarize recent developments in this area.