24 Because combinations of mutations appear to dictate the phenotype and possibly the clinical behavior of the disease, it is likely that in the future prognostic predictions will be based on the simultaneous study of a higher number of genes. 145 This multigene analysis has been so far difficult to perform using conventional methods (e.g. PCR, Sanger sequencing and fragment this website analysis) but it becomes now feasible through NGS techniques. The multigene approach has recently resulted in two new prognostic models of AML.[146] and [147] These results represent a step forward the molecular classification of AML but

the prognostic values of mutations affecting the IDH1/IDH2, DNMT3A and TET2 genes remain controversial since they were found

to be prognostically significant in one study 146 but not in another. 147 The three currently proposed models for prognostic stratification of AML based on combined molecular and cytogenetics criteria [24] and [146] or solely on molecular parameters 147 are shown in Table 2. AML, with the exception of acute promyelocytic leukemia, is still treated using conventional chemotherapy (usually the 3 + 7 regimen) with/without allogeneic HSCT.148 Bioactive Compound Library supplier This approach results into cure of about 40% of younger adult patients and about 10-15% of older (> 60 years) patients. Full determination by NGS studies of the mutational landscape of AML and the understanding of the role played by gene mutations in leukemogenesis is likely to provide the basis for the development of new drugs and for a more rationale use of the already existing anti-leukemic agents. Because most AML cases carry concomitant mutations it is likely that a combinatorial therapy based on the use of drugs targeting the different affected pathways will be the winning strategy. As an example,

in NPM1-mutated AML, one could think to use small molecules interfering with the functions of nucleophosmin (oligomerization and nucleo-cytoplasmic transport) in association with drugs interfering with cell signaling (when a concomitant FLT3-ITD mutation is present) or with agents acting on epigenetic alterations (if DNMT3A or IDH1 mutations are present). Brunangelo Falini applied for a patent on clinical use of NPM mutants. The other Authors have no potential conflict of interest. Supported by the Associazione GNAT2 Italiana per la Ricerca sul Cancro (A.I.R.C.) (Grant n. IG 10111) and Fondazione Cassa di Risparmio di Perugia (Grants n. 2008.020.058 and 2009.010.0462). We would like to thank Dr. Raul Rabadan Department of Biomedical Informatics, Center for Computational Biology and Bioinformatics, Columbia University, New York, USA, for critically reading the manuscript. We apologize to those whose papers could not be cited owing to space limitation. “
“The release of vesicles by cells is a common and evolutionary conserved process, because both prokaryotes[1] and [2] and eukaryotic cells[3] and [4] release such vesicles into their environment.

Darüber hinaus zeigen in-vitro-Daten,

dass Mn an der Induktion der Ausbildung von Zellfortsätzen durch die Astrozyten beteiligt ist [5]. Mn liegt in verschiedenen NVP-BKM120 cost chemischen Formen vor, darunter verschiedene Oxidationsstufen (Mn2+, Mn3+, Mn4+, Mn6+, Mn7+), Salze (Sulfate und Gluconate) und Chelate (Aspartate, Fumarate, Succinate). Die vielfältigen chemischen Eigenschaften von Mn ermöglichen seine industrielle Verwendung bei der Herstellung von Glas und Keramik, in Klebmitteln, beim Schweißen, in Farben, in Antiklopfmitteln für Benzin (Methylcyclopentadienyl-Mangan-Tricarbonyl, MMT) und für viele weitere Zwecke. Mn-Mangel ist zwar selten, kann aber zu Geburtsfehlern, Fortpflanzungsstörungen, Knochenmissbildungen, Schwäche und einer erhöhten Anfälligkeit für Krampfanfälle beitragen [6] and [7]. Die Aufnahme von Mn erfolgt in der Hauptsache durch die Ernährung, dermale Resorption und Inhalation. Mn findet sich in der Nahrung vor allem in Vollkorn, Nüssen und Samen, Tee, Gemüse, Ananas und Bohnen. Ungeachtet seiner essenziellen Funktion bei vielerlei Stoffwechselprozessen kann sich Mn bei übermäßiger Exposition im Gehirn anreichern und dort Funktionsstörungen des Basalgangliensystems verursachen, die zu einer schweren, dem PS ähnlichen neurologischen Erkrankung

führen [8]. Der Mn-Gehalt im Gehirn liegt bei etwa 1-2 g/g Trockengewicht. Bei extremer Exposition variiert die Konzentration von Mn je nach Gehirnregion. Es ist wichtig festzuhalten, dass der höchste Mn-Spiegel Progesterone beim Menschen im Globus pallidus Selleck AZD2014 und bei Ratten im Hypothalamus gefunden wird [9] and [10]. Übermäßige und langfristige Exposition gegenüber

Mn im Rahmen einer Tätigkeit z. B. als Schweißer oder im Bergbau, durch Inhalation von Verbrennungsprodukten des Antiklopfmittels MMT in Treibstoff oder aufgrund hoher Mn-Konzentrationen in Grund- oder Quellwasser führt zu Akkumulation von Mn in den dopaminreichen Regionen der Basalganglien. Tatsächlich wurde durch spektroskopische Untersuchungen an Ratten gezeigt, dass sich nach Exposition die höchsten Mn-Mengen in den Mitochondrien der Basalganglien anreichern [11] and [12]. Dies verursacht eine klinische Störung, die als Manganismus bezeichnet wird und die durch eine Reihe extrapyramidaler Symptome gekennzeichnet ist, die denen des idiopathischen Parkinson-Syndroms (IPS) ähneln, wie z. B. Anorexie, Apathie und Muskel- und Gelenkschmerzen. Kurz nach Einsetzen dieser Symptome zeigen die Patienten außerdem Gedächtnisverlust, Zwangshandlungen, Sehstörungen, Sinnestäuschungen und Wahnvorstellungen sowie Verwirrtheit, was klinisch als „Locura manganica” oder „Mangan-Verrücktheit” bezeichnet wird [13]. Mn-Überladung schädigt zwei lebenswichtige Organe, das Gehirn und die Lunge, das letztere infolge von Inhalation [14] and [15].

Data collection and detection of illegal activity has been a challenge, especially in the vast areas of operation in the Indian Ocean and the Western Pacific. A recent air, sea and electronic surveillance operation selleck chemicals llc over an area of approximately 30 million square kilometers conducted by

the Secretariat of the Pacific Community (SPC) and the Pacific Islands Forum Fisheries Agency (FFA) resulted in the boarding of 64% of 320 sighted vessels and 27 (13%) infringements. The operation included the Cook Islands, Micronesia, Kiribati, Marshall Islands, Nauru, Niue, Palau, Samoa, Solomon Islands, Tokelau, Tonga, Tuvalu and Vanuatu: regional estimates put lost earnings from activities such as under-reporting or misreporting to as much as over a billion dollars [78]. Under-reporting and misreporting of catches, even by European flagged vessels, [79] remain a significant challenge in the Indian Ocean where more than half of tuna catches are made by small-scale gears [80]. Gillnet fisheries continue to expand rapidly in

the Indian Ocean, some of which use illegal large-scale pelagic driftnets [81]. A report on the global tuna supply chain stated that in June 2010 around 30% of Thailand’s imported tuna had catch certificates to comply with EU fishing regulations designed to exclude IUU fish from the supply chain [82]. However, exports to the EU account for less than 20% of Thai canners׳ selleckchem total production and Thai industry sources indicated that while “it would be ideal if all imports had EU catch documentation, market outlets still exist for canned tuna using fish supplies that do not have EU-compliant catch certificates,”[83] suggesting that the USA may remain a major market for tuna that does not have catch certificates. The Philippines second is the second largest canned tuna exporter in Asia after Thailand. Unlike the Thai tuna industry that largely depends on imports of tuna raw material for its

canneries, the Philippines has a large domestic tuna fishing fleet that supplies most of the raw materials to its canneries. About 50% of landed tuna is consumed locally, and the other half is either exported as sashimi-grade tuna or sent to tuna processing plants [84]. The Philippines increasingly imports significant amounts of tuna from foreign fleets to top up supplies from domestic tuna fishing vessels. A recent report in the Philippine media noted that the declining fish catch in the inshore waters of the country has driven Filipino fishers further offshore, resulting in increased costs, higher safety risks and more difficulty in sourcing high-quality tuna [85]. There is under-reporting of tuna catches from smaller vessels operating in provincial waters and losses from illegal fishing by foreign operators may be as high as 10,000 t each year in the Philippines EEZ [86].

akashiwo blooms elsewhere in the world. Yamatogi et al. (2006) recorded the appearance of H. akashiw in Isahaya Bay at water temperatures of 18.1–31.5 °C buy Alectinib and salinities of 23.60–34.78‰. Lee & Kim (2008) found H. akashiwo in Wonmun bay at temperatures of 19.5–29.8 °C and salinities of 22.4–31.81‰. The absence of a correlation between temperature and the Heterosigma bloom in the present study is reliable, as the

water temperatures throughout the study period were within the optimal range (≥ 15 °C) for Heterosigma growth. Therefore, it is unlikely that water temperature was a major factor regulating fluctuations of H. akashiwo during the present investigation period. That the disappearance of H. akashiwo blooms from Saudi waters followed the increase in salinity to more than 40‰ indicates that this strain of Heterosigma could not tolerate or adapt to such high salinities. Pexidartinib The disappearance of a H. akashiwo bloom following a salinity increase was previously investigated in Hakata Bay, Japan ( Shikata et al. 2008). This observation is also consistent with other studies reporting that the highest salinity level at which the lowest level of

growth of H. akashiwo is attained is 40‰ ( Haque and Onoue, 2002 and Lee et al., 2005). In this regard, it has been stated that Heterosigma strains have the physiological ability to adapt exceptionally Janus kinase (JAK) quickly to the range of salinities characteristically encountered in their natural environments ( Honjo 2004). However, salt stress could affect the physiology of Raphidophyceae ( Zhang et al. 2006), as has been reported for cyanobacteria, through iron imbalances and/or induced nutrient deficiencies ( Shukla et al. 1997). In addition to salinity, the decline of H. akashiwo blooms can be attributed to the attack of specific bacteria and viruses (Lawrence et al. 2001, Tomaru et al. 2004) and to grazing by ciliates and heterotrophic dinoflagellates

( Jin Jeong et al. 2003). Of greater interest in this study is that the abundance of H. akashiwo showed a strong positive correlation with nutrient concentrations of NH4, NO3 and PO4. This finding supports the hypothesis that bloom stimulation by nutrients may be a general feature of HAB taxa ( Heisler et al. 2008). Specifically, H. akashiwo abundance is favoured over competing co-occurring phytoplankton under conditions of enhanced PO4, NH4 and NO3 ( Zhang et al. 2006). Remarkably, no algal species except Chattonella was found during the H. akashiwo bloom in Saudi waters during the present study. Previously, Heterosigma blooms had been found as monospecies in the Salish Sea ( Rensel et al. 2010), and this may be due to the allelopathic activity of Heterosigma inhibiting or even excluding co-occurring phytoplankton and other organisms ( Yamasaki et al., 2007 and Yamasaki et al., 2009).

Linkage group B06 also has few major R-genes [9], with the notable exception of Ur-4, despite its apparent abundance of RGH sequences. The position of bc-3 was not considered, as this is a recessive R-gene that has been suggested to be related to a family of elongation initiation factors [56]. However, the Ur-4 gene, as well as a QTL, for white mold [9] was observed to lie in the same region as BMr51 to BMr302. Linkage group B07 contained Phs, a phaseolin-encoding

locus associated with a common bacterial blight QTL, as well as 4 RGH-SSR plus RGH4b, in the region suspected to contain the R-genes (Co-5, Co-6) and further QTL for anthracnose and common bacterial blight resistance. The three

R-genes and multiple QTL on linkage group B08 aligned well with RGH genes. Co-4, although suspected to be a protein kinase gene, was near the loci RGH15a and RGH15c along with QTL for common Cyclopamine manufacturer Fulvestrant cost bacterial blight and white mold resistance. QTL for resistance to the same diseases plus a QTL for anthracnose resistance were near RGH2, BMr244, and BMr269 and a previously unmapped RGH-RFLP named EcoRV334, which was in the region containing the Phg-2 (angular leaf spot) and Ur-13 (rust) resistance genes [9]. The next two linkage groups were contrasting, in that B09 had few RGH-SSR (3) and few QTL for resistance, while B10 had a large number of RGH genes (10) and many QTL for various diseases. Linkage group B10 has emerged as being very important for angular leaf spot resistance. One report cites anthracnose resistance in the middle of B10 although this is unconfirmed

in other studies [34]. Major R-genes for angular leaf spot on B10 could be analyzed Cyclin-dependent kinase 3 in relation to Phg-1, a new Andean R-gene on B01 [57]. The final chromosome-linkage group B11, especially the end of the long arm, has been long known to be a hotspot for R-genes [9]. From the bottom of B11, there was alignment of BMr207 and RGH1a with Co-2, Ur-3, Ur-11, and Ur-Dorado [9]. Two other major R-genes for rust, Ur-6 and Ur-7, along with common bacterial blight and web blight QTL, are likely to be tagged by 5 RGH-SSR markers in a more proximal location on the chromosome B11 and in the upper part of the linkage group B11 another QTL for common bacterial blight may align with marker BMr281. In summary, this work established the position of new RGH-SSR markers relative to known R-genes. A large number of RGH-related markers have been developed, including 32 from the BAT93 × Jalo EEP558 population [48], 21 from the Dorado × XAN 176 population [50], and 14 from the Calima × Jamapa population [58]. Mutlu et al. [59] coincidentally mapped 32 RGAP bands in the first of these populations and also detailed alignment with QTL and R-genes.

The average values of TP, SD, Chl a, TN and TN:TP measured in the surface

waters in summer ( Kajak 1983, Zdanowski 1983) were also APO866 research buy used in the assessment of the Vistula Lagoon’s trophic state. Vollenweider’s method for assessing a water body’s trophic state (1989), accepted by the Organization for Economic Co-Operation and Development (OECD) and based on the average values of selected parameters measured in spring and summer, was also applied. Samples for the microscopic determination of phytoplankton were fixed with Lugol’s solution. Phytoplankton was analysed under an inverted microscope (Nikon TMS, Tokyo, Japan) with 200×, 400× and 600× magnification. The counting units (N) were cells, coenobia or trichomes 100 μm in length. To calculate the biomass, the species were approximated to simple geometric or combined forms. Counting and biomass determination were performed in accordance with the recommendations of the Baltic Monitoring Programme ( HELCOM). The average concentration of total phosphorus (TP) during buy Everolimus the whole measurement period was 160.32 ± 61.18 μg P dm−3; in summer it exceeded 180 μg P dm−3. The phosphorus content in the water was the highest in 2009 (av. 169 μg P dm−3). The concentration of chlorophyll a was extremely variable, the highest value being noted in 2008 (54 μg dm−3).

The total nitrogen content of Vistula Lagoon waters was stable in 2008–2009 at an average level of 1.36 mg N dm−3; the average level in 2007 was lower – 0.86 mg N dm−3. During the study period the average salinity was most ∼ 3.7 PSU, the water transparency low, the oxygen content high and the mean water temperature 18°C. The average value of the TN:TP ratio was < 10, but the maximum value was slightly in excess of 20 in June 2008 ( Table 1). The trophic state indices calculated for the

summer months of 2007–2009 for the surface waters were: TSI (Chl a) 53–90, TSI (TP) 71–89, TSI (TN) 41–65 and TSI (SD) 65–83. These values are high, indicating that the Vistula Lagoon is at least eutrophic. The combined trophic index was the highest in 2009. The average value of TSI (TP) was 80, and even exceeded 82 in July. The mean value of TSI (Chl a) was also high (78) and in July it was 83. The same tendency was observed in the case of TSI (SD), its highest value being noted in June (83). The trophic states of the Vistula Lagoon waters were determined on the basis of the four classification systems described above and are presented in Table 2. The values of TSI were calculated based on the formulas given below the table. Analysis of the phytoplankton revealed a significant contribution of planktonic blue-green algae, especially colonial species with picoalgal and larger cell sizes belonging to the Chroococcales, Oscillatoriales and the typical bloom-forming Nostocales.

The complex (1:1) was obtained by co-evaporation. MGN and β-CD, in an equimolar ratio (1:1) were added to an aqueous solution prepared with 5 mL ethanol/100 mL water. The solution was protected from light and mechanically shaken at 170 rpm at 25 °C in a Marconi MA-420 incubator shaker (São Paulo, Brazil) for 24 h. After evaporation of the ethanol from the reaction mixture, the uncomplexed MGN was removed by filtration. Then,

Pexidartinib cell line water was evaporated under reduced pressure in a Büchi Rotavapor (Büchi, Germany) and dried in vacuum, giving the MGN:β-CD complex. The FT-IR spectra of MGN, β-CD and MGN:β-CD complex were recorded at room temperature in a spectral region between 4000 and 500 cm−1 on an IRPrestige-21, Fourier Transform Spectrometer (Shimadzu, Kyoto, Japan). Samples were prepared as small pellets by mixing each of them in a mortar with KBr (1:100) and then pressed. A blank KBr disc was used as a background. DSC analysis was carried out for MGN, β-CD and the complex with a DSC-60 calorimeter (range 25–500 °C) (Shimadzu, Kyoto, Japan). The temperature scale selleckchem was calibrated using α-alumina powder. Samples (5.0–10.0 mg) were

placed in standard aluminum pans and measurements were performed at a heating rate of 5 °C min−1 from 25 to 400 °C in a dynamic nitrogen atmosphere (flow rate = 20 mL/min). The MGN and MGN:β-CD complex were prepared with 5 mL ethanol/100 mL water. The solution of the MGN:β-CD (1:1) complex was prepared at concentrations of 50, 100 and 500 μmol L−1. The solutions were stirred (170 rpm) for 24 h at 25 °C. Initially, a concentration of 100 μmol L−1 for the solution of DPPH in only methanol was used. In order to analyze solvent effects, the concentrations of 100 μmol L−1 for MGN and 50 μmol L−1 for DPPH were used. The antioxidant activities of MGN, β-CD, MGN:β-CD complex samples and GA (positive control) were measured in terms of their radical scavenging ability (RSA), using the DPPH method. Carbohydrate MGN,

β-CD or MGN:β-CD complex solutions (0.30 mL) were mixed with 2.7 mL of 50 μmol L−1 DPPH solution in different proportions of methanol:water and ethanol:water (20:80, 30:70, 50:50 and 100:0 mL:mL) in a 3 mL-quartz cuvette. The DPPH absorption values were obtained at 516 nm every 5 min, during 50 min by UV–vis spectrophotometer (MultiSpec-1501, Shimadzu, Japan). The results are expressed as remaining DPPH R (%) as a function of time (Oliveira et al., 2009). All measurements were performed in triplicate. The MGN, β-CD and MGN:β-CD (1:1) complex aqueous solutions were prepared with 5 mL ethanol/100 mL water at a concentration of 100 μmol L−1. The solution was stirred (170 rpm) for 24 h in the absence of light. The ORAC analyses were carried out on a Synergy HT multidetection microplate reader, from Bio-Tek Instruments, Inc. (Winooski, USA), using 96-well polystyrene white microplates, purchased from Nunc (Denmark).

6, MSE = 1988, Navitoclax ic50 p = .07]. Further analysis revealed a significant number-line compatibility effect (i.e., faster responses to compatibly posited pairs than to incompatibly posited pairs) for synesthetes [F (1, 16) = 7.3, MSE = 1,988, p = .025] but not for controls [F (1, 16) = 1, MSE = 1,988, ns]. Groups did not differ in any other aspect beside this one. No other main effects or interactions were found ( Fig. 2A). A significant main effect for dimension congruency was found [F (2, 32) = 15.2, MSE = 366, p < .0001] and for number-line compatibility [F

(1, 16) = 7.3, MSE = 148, p < .025]. The interaction between congruency and compatibility was found to be significant as well [F (2, 32) = 15.2, MSE = 143, p < .0001]. Unfortunately, this time the triple interaction between congruency, compatibility and group did not reach conventional significance [F (2, 32) = 1.9, MSE = 143, p = .16], nevertheless, with adherence to our predictions, we wished to examine more closely whether the congruency effect was modulated by number-line compatibility differently for each group, and thus we further analyzed this interaction. As can be infer from the non significant 3-way interaction, both synesthetes and controls displayed a significant 2-way interaction between congruency effect and number line compatibility [F (1, 16) = 9.1, MSE = 212, p < .01; F (1, 16) = 8.1, MSE = 212, click here p < .025, for synesthetes

and controls, respectively]. Further analysis of these interactions revealed a significant congruency effect in both number-line compatibility conditions for the controls, although it was 22 msec smaller for Evodiamine the incompatible condition [F (1, 16) = 16.5, MSE = 307, p < .001] than for the compatible one [F (1, 16) = 38.7, MSE = 438.3, p < .0001]. In contrast, for the synesthetes, a significant congruency effect was evident only in the number-line compatible condition [F (1, 16) = 8.2,

MSE = 438, p < .025], but crucially, no congruency effect was found in the number-line incompatible condition [F (1, 16) < 1, ns] ( Fig. 2B). Again, as before, we conducted a statistical power analysis that revealed a required minimum sample size of 277 participants in order to achieve a significant effect. In the numerical comparison the only significant effect found was for congruency [F (2, 32) = 42.7, MSE = .002, p < .0001], indicating that both synesthetes and controls displayed a significant congruency effect regardless of number-line compatibility. In the physical comparison, there was a main effect for group [F (1, 16) = 7.7, MSE = .002, p < .025], for congruency [F (2, 32) = 28.9, MSE = .0005, p < .0001] and for number-line compatibility [F (1, 16) = 4.9, MSE = .0003, p < .05]. In addition, number-line compatibility also interacted with group [F (1, 16) = 4.9, MSE = .0003, p < .05]. This interaction was the result of a significant compatibility effect (i.e.

An example of this is the reaction of fishers towards poachers. Management and protection of the resource are viewed as a personal interest by the fishers, thus generating a sense of empowerment. Hence, the fishers are invested in the resource and do not hesitate in implementing their own surveillance. The same phenomenon occurred in the loco fishery in Chile [8], where it reduced costs and allowed for a more effective

control. These events demonstrate how the implementation of the co-management system has aided in creating social capital, which is essential to the success of any fishery [4] and [40]. The co-management system exerted an effect in markets when it first started commercializing barnacles and selleck compound it still continues to drive market cycles. Gooseneck barnacles in Asturias have evolved since the establishment of the system from being an under-commercialized resource to reaching prices of over 200 euros/kg in Asturian markets. Through the establishment of a co-management system with spatial property rights the fishery managed to avoid the tragedy of the commons [13] found in open access markets, the common system in European fisheries, by incentivizing the

exploitation and stewardship of a pristine resource. The fishing season was established based on fishers׳ knowledge and scientific information available, particularly P. pollicipes reproductive cycle. Moreover, the fishing season and market cycles have mutually affected each other. A relationship between supply and demand was observed and has been incorporated into the guidelines by maintaining fishers׳ daily Tofacitinib ic50 TAC in 8 kg during the peak market season (December). Despite

these measures Neratinib ic50 there is not enough supply to meet the increased demands of the season resulting in a pronounced mean price increase. For the rest of the campaign supply and demand are balanced and prices stabilize. During the summer period, only the Cabo Peñas plan remains open, while market prices decline with regard to those in the high or mid seasons. Another characteristic of the system that drives market forces is the establishment of bans. Good quality zones with higher commercial value are submitted to partial bans and are only harvested during the high season. This strategy ensures that the best resource will be sold at the highest price thus raising market prices. An effect of fishers short-term decisions on market demands has been documented in other small-scale fisheries [5] and [41]. According to Gutiérrez et al. [2], in the most accomplished co-management systems the market is influenced by the fishers, as is the case in Asturias. Adaptive management has been broadly accepted as a desirable condition for natural resource management systems [39], it enhances the resilience of managed natural resources by accounting for their unpredictability [39].

As the pure antigen is not accompanied by any of the elements that activate the defensive triggers of the innate immune system that would be present in the native pathogen, this approach results in an antigen that is well tolerated, but Baf-A1 usually requires the addition of an adjuvant in order to achieve high immunogenicity and long-term protection. A peptide antigen approach represents an additional step to the protein antigen approach. Peptide antigens may prove beneficial in the context of diseases where the pathogen evolves and protective antigens are numerous. In this setting, mixtures of different peptides known to be targets for protective immunity can be

used more efficiently than producing many different full-protein antigens. It is possible to identify and directly synthesise by various methods specific peptides that elicit adaptive immune responses. The peptides selected for vaccine development must contain epitopes that induce sufficient priming of naïve T cells to attain effective cellular and humoral immunity. Innate ‘defensive triggers’ may be conserved molecular structures, such as repeating units of carbohydrate moieties, certain nucleic selleck chemicals llc acid sequences, or molecules that are

recognised by specialised pathogen receptors on innate immune cells and certain other cell types. The activation of immune defence mechanisms requires the presence of both antigen and defensive triggers to communicate the nature of the potential threat and to induce adequate immune responses. These elements may be missing in subunit and recombinant vaccine antigens and, for that reason, the addition of adjuvants and/or alternative ways of helping the antigens to stimulate the immune system are needed. Influenza vaccine technology encompasses most

of the current approaches to antigen selection, including the use IMP dehydrogenase of whole viruses (Figure 3.7). The natural immune response to influenza viruses involves both humoral and cell-mediated immunity and the type-1 interferon response that is important for viral clearance. The humoral immune response is normally of more importance after viral clearance, and antibody responses associated with the immunoglobulin (Ig) G and IgA isotypes are important for protection against reinfection or infection with a new strain. Antibody against the haemagglutinin (HA) protein (a glycoprotein responsible for binding the virus to host cells) is considered the primary immune mediator of protection as this can inhibit virus binding to the epithelium, and thus block the early stages of infection. Antibody to the neuraminidase (NA) protein has also been considered as it can prevent cell-to-cell spread of the virus within the host. The evaluation of haemagglutinin inhibitory (HI) antibody titres has been used from the very beginning to assess influenza vaccine immune-protective abilities.