Phenotypic novelty in experimental hybrids is predicted by the genetic distance between species of cichlid fish.

BACKGROUND: Transgressive segregation describes the occurrence of novel phenotypes in hybrids with extreme trait values not observed in either parental species. A previously experimentally untested prediction is that the amount of transgression increases with the genetic distance between hybridizing species. This follows from QTL studies suggesting that transgression is most commonly due to complementary gene action or epistasis, which become more frequent at larger genetic distances. This is because the number of QTLs fixed for alleles with opposing signs in different species should increase with time since speciation provided that speciation is not driven by disruptive selection. We measured the amount of transgression occurring in hybrids of cichlid fish bred from species pairs with gradually increasing genetic distances and varying phenotypic similarity. Transgression in multi-trait shape phenotypes was quantified using landmark-based geometric morphometric methods. RESULTS: We found that genetic distance explained 52% and 78% of the variation in transgression frequency in F1 and F2 hybrids, respectively. Confirming theoretical predictions, transgression when measured in F2 hybrids, increased linearly with genetic distance between hybridizing species. Phenotypic similarity of species on the other hand was not related to the amount of transgression. CONCLUSION: The commonness and ease with which novel phenotypes are produced in cichlid hybrids between unrelated species has important implications for the interaction of hybridization with adaptation and speciation. Hybridization may generate new genotypes with adaptive potential that did not reside as standing genetic variation in either parental population, potentially enhancing a population's responsiveness to selection. Our results make it conceivable that hybridization contributed to the rapid rates of phenotypic evolution in the large and rapid adaptive radiations of haplochromine cichlids.

Validation of the antenatal perceived stress inventory

This article presents the Antenatal Perceived Stress Inventory. The originality of this scale is to assess the impact of events experienced during pregnancy on the stress perceived by mothers. Scale validation was performed using data from 150 French-speaking nulliparous mothers and collected between 36 and 39 weeks of gestation (T1), and between 2 days (T2) and 6 weeks postpartum (T3). Factor analysis revealed a hierarchical three-factor structure that closely fit the data, including medical and obstetric risks/fetal health (F1), psychosocial changes (F2), and the prospect of childbirth (F3). The Antenatal Perceived Stress Inventory is a valid French prenatal stress scale with good psychometric properties.

La voix de M. Raymond Poincaré, Président de la République française : discours prononcé le 14 juillet 1915

[Discours. 1915-07-14]

A non-interventional phase IV Belgian survey to assess the antiviral effectiveness of pegylated interferon-alpha-2b and ribavirin treatment according to the stage of liver fibrosis in previously untreated patients with genotype 1/4/5/6 chronic hepatitis C (PRACTICE).

BACKGROUND AND STUDY AIMS: This was an observational, non-interventional, multicenter, phase IV study, in patients with genotype 1/4/5/6 chronic hepatitis C (CHC). The primary objectives were to evaluate SVR in patients with no or minimal fibrosis (METAVIR F0-F1) versus well established fibrosis (F2-F4), and to estimate response on Weeks 12, 24 and 48 on treatment in previously untreated patients with genotypes 1/4/5/6 CHC. PATIENTS AND METHODS: 538 patients treated with pegylated interferon alfa 2b 1.5 mcg/kg in combination with ribavirin 800-1200 mg/day were enrolled in 55 sites in Belgium and Luxembourg, 505 being considered for the analysis. 40% of the patients were female and 60% male, the average age was 47.5 years, 10.5% were 65 or older. RESULTS: SVR was observed in 35% of the patients, EVR in 68%, of which pEVR in 33% and cEVR in 35%. SVR was observed in 43% of the low fibrosis group (F0, F1) and 30% of the high fibrosis group (F2, F3, F4) (p = 0.005). SVR rates were 34% for genotype 1, 37% for genotype 4, and 47% for genotype 5 (NS). Multivariate analysis showed that EVR and baseline METAVIR score are independent prognostic factors for SVR. CONCLUSIONS: This trial confirms that fibrosis stage and early viral response are the most important key-factors to predict sustained response, suggesting that the earlier patients are treated, the better the outcome. Non-invasive techniques enable us to closely monitor progression of fibrosis, allowing a better selection of patients for antiviral treatment in the DAA-era.

PCR-RAPD and PCR-RFLP polymorphisms detected in Anopheles cruzii (Diptera, Culicidae)

The aim of the present study was to examine genetic variability in populations of An. cruzii by employing PCR-RAPD and PCR-RFLP markers. All analyses were carried out using individuals of the F1 generation of wild caught females obtained in Santa Catarina State (Florianópolis and São Francisco do Sul), Paraná State (Morretes, Paranaguá and Guaratuba) and São Paulo State (Cananéia). In the PCR-RAPD experiments, seven primers were used for comparisons within and among populations. The restriction profile of the ITS2 including a fragment of both 5.8S and 28S regions of the rDNA was obtained with the enzymes BstUI, HaeIII, TaqI, HhaI, Sau96I, HinfI, HincII and NruI. The PCR-RAPD method detected a large number of polymorphic bands. Genetic distance among populations of An. cruzii varied from 0,0214 to 0,0673, suggesting that all individuals used in the analyses belong to a single species. The number of migrants per generation (Nm) was 4.3, showing the existence of gene flow among populations. The restriction profile of the ITS2, 5.8S and 28S gene regions was similar in all An. cruzii samples, whereas the results obtained by using HhaI and NruI are indicative that the individuals analyzed have nucleotide sequences distinct from those of An. cruzii samples from Peruíbe and Juquiazinho deposited in GenBank.

Epidemiologia Molecular, Evolução Viral e Perfil de Resistência aos Antirretrovirais em uma População de Pacientes Infectados por Hiv-1 e/ou Hiv-2 Residentes em Diferentes Ilhas do Arquipélago de Cabo Verde

O diagnóstico sorológico da infecção pelo HIV-1 e HIV-2 teve início em Cabo Verde em 1987, mas pouco se sabe a respeito da diversidade genética desses vírus nessas ilhas, localizadas na costa Ocidental Africana. Neste estudo, caracterizamos a epidemiologia molecular do HIV-1 e HIV-2 em Cabo Verde, analisamos a origem dos principais clados de HIV introduzidos no país e descrevemos a ocorrência de mutações de resistência aos antirretrovirais (DRM) em indivíduos virgens de tratamento (ARTn) e pacientes em tratamento (ARTexp) oriundos das diferentes ilhas. Amostras de sangue, dados sociodemográfico e clínico-laboratoriais foram obtidos de 221 indivíduos HIV positivos entre 2010-2011. As amostras foram sequenciadas na região da polimerase (1300 pares de bases) e análises filogenéticas e de bootscan foram realizadas para a subtipagem viral. Os algoritmos disponibilizados nos sites Stanford HIV Database e HIV-GRADE e.V. Algorithm Homepage foram utilizados para avaliar a existência de DRM em pacientes positivos para HIV-1 e HIV-2, respectivamente. Os estudos evolutivos e filogeográficos foram realizados através do programa BEAST. Entre os 221 pacientes analisados, sendo 169 (76,5%) HIV-1, 43 (19,5%) HIV-2 e 9 de (4,1%) co-infectados pelo HIV-1 e pelo HIV-2, 67% eram do sexo feminino. As medianas de idade foram de 34 (IQR = 1-75) e 47 (IQR = 12-84) para o HIV-1 e HIV-2, respectivamente. A infecção pelo HIV-1 é causada pelo subtipo G (36,6%), CRF02_AG (30,6%), subtipo F1, (9,7%), URFs (10,4%), subtipo B (5,2%), CRF05_DF (3,0%), subtipo C (2,2%), CRF06_cpx (0,7%), CRF25_cpx (0,7%) e CRF49_cpx (0,7%), e todas as infecções por HIV-2 pertencem ao grupo A. De acordo com as análises filogeográficas e de origem do HIV, estima-se que o HIV-2 foi o primeiro tipo viral introduzido em Cabo Verde e possui relações filogenéticas com sequências referências de Portugal. O HIV-1 entrou no país mais tarde, primeiramente pelo subtipo G, evidenciando relações com sequências da África Central e de Portugal. Transmissão de DRM (TDRM) foi observada em 3,4% (2/58) de pacientes HIV-1 ARTn (1,7% NRTI, NNRTI 1,7%), mas não entre os infectados com HIV-2. Entre os pacientes ARTexp, DRM foi observada em 47,8% (33/69) dos infectados pelo HIV-1 (37,7% NRTI, NNRTI 37,7%, 7,4% de PI, 33,3% para duas classes) e 17,6% (3/17) nos infectados pelo HIV-2 (17,6%, 11,8% NRTI PI, 11,8% para ambas as classes). Este estudo indica que Cabo Verde tem um cenário epidemiológico molecular complexo e único dominado pelo HIV-1 subtipo G, CRF02_AG e F1 e HIV-2 grupo A, sendo esse o primeiro tipo viral introduzido em Cabo Verde. A ocorrência de TDRM e o nível relativamente elevado de DRM entre os pacientes tratados constituem uma preocupação, pelo que o monitoramento contínuo dos pacientes em ARTexp, incluindo genotipagem são políticas públicas a serem implementadas.

Loss of phenotypic plasticity generates genotype-caste association in harvester ants.

Caste differentiation and reproductive division of labor are the hallmarks of insect societies. In ants and other social Hymenoptera, development of female larvae into queens or workers generally results from environmentally induced differences in gene expression. However, several cases in which certain gene combinations may determine reproductive status have been described in bees and ants. We investigated experimentally whether genotype directly influences caste determination in two populations of Pogonomyrmex harvester ants in which genotype-caste associations have been observed. Each population contains two genetic lineages. Queens are polyandrous and mate with males of both lineages , but in mature colonies, over 95% of daughter queens have a pure-lineage genome, whereas all workers are of F1 interlineage ancestry. We found that this pattern is maintained throughout the colony life cycle, even when only a single caste is being produced. Through controlled crosses, we demonstrate that pure-lineage eggs fail to develop into workers even when interlineage brood are not present. Thus, environmental caste determination in these individuals appears to have been lost in favor of a hardwired genetic mechanism. Our results reveal that genetic control of reproductive fate can persist without loss of the eusocial caste structure.

Molecular epidemiology and evolution of HIV-1 in Portugal and portuguese speaking african countries

The aims of this thesis were to better characterize HIV-1 diversity in Portugal, Angola, Mozambique and Cape Verde and to investigate the origin and epidemiological history of HIV-1 in these countries. The impact of these issues in diagnosis, disease progression and susceptibility to ARV therapy was also investigated. Finally, the nature, dynamics and prevalence of transmitted drug resistance (TDR) was determined in untreated HIV-1 infected patients. In Angola, practically all HIV-1 genetic forms were found, including almost all subtypes, untypable (U) strains, CRFs and URFs. Recombinants (first and second generation) were present in 47.1% of the patients. HIV/AIDS epidemic in Angola probably started in 1961, the major cause being the independence war, subsequently spreading to Portugal. In Maputo, 81% of the patients were infected with subtype C viruses. Subtype G, U and recombinants such as CRF37_cpx, were also present. The results suggest that HIV-1 epidemic in Mozambique is evolving rapidly in genetic complexity. In Cape Verde, where HIV-1 and HIV-2 co-circulate, subtype G is the prevailed subtype. Subtypes B, C, F1, U, CRF02_AG and other recombinant strains were also found. HIV-2 isolates belonged to group A, some being closely related to the original ROD isolate. In all three countries numerous new polymorphisms were identified in the RT and PR of HIV-1 viruses. Mutations conferring resistance to the NRTIs or NNRTIs were found in isolates from 2 (2%) patients from Angola, 4 (6%) from Mozambique and 3 (12%) from Cape Verde. None of the isolates containing TDR mutations would be fully sensitive to the standard first-line therapeutic regimens used in these countries. Close surveillance in treated and untreated populations will be crucial to prevent further transmission of drug resistant strains and maximize the efficacy of ARV therapy. In Portugal, investigation of a seronegative case infection with rapid progression to AIDS and death revealed that the patient was infected with a CRF14_BG-like R5-tropic strain selectively transmitted by his seropositive sexual partner. The results suggest a massive infection with a highly aggressive CRF14_BG like strain and/or the presence of an unidentified immunological problem that prevented the formation of HIV-1-specific antibodies. Near full-length genomic sequences obtained from three unrelated patients enabled the first molecular and phylogenomic characterization of CRF14_BG from Portugal; all sequences were strongly related with CRF14_BG Spanish isolates. The mean date of origin of CRF14_BG was estimated to be 1992. We propose that CRF14_BG emerged in Portugal in the early 1990s, spread to Spain in late 1990s as a consequence of IDUs migration and then to the rest of Europe. Most CRF14_BG strains were predicted to use CXCR4 and were associated with rapid CD4 depletion and disease progression. Finally, we provide evidence suggesting that the X4 tropism of CRF14_BG may have resulted from convergent evolution of the V3 loop possibly driven by an effective escape from neutralizing antibody response.

Bioactivity of Indonesian mahogany, Toona sureni (Blume) (Meliaceae), against the red flour beetle, Tribolium castaneum (Coleoptera, Tenebrionidae)

Bioactivity of Indonesian mahogany, Toona sureni (Blume) (Meliaceae), against the red flour beetle, Tribolium castaneum (Coleoptera, Tenebrionidae). The insecticidal activity of Toona sureni (Blume) Merr. was evaluated considering repellency, mortality and progeny production of F1 adults of Tribolium castaneum (Herbst, 1797) (Coleoptera, Tenebrionidae). Dried extract of seeds of T. sureni was dissolved in acetone to prepare solution of various concentrations (0.5, 1.0, 2.5 and 5.0%). To test for repellency, the insects were exposed to treated filter paper. Mortality of larvae, pupae and adults was evaluated by the treatment of spraying the insects with different concentrations of T. sureni extract. Residual effect of the extract was also evaluated considering the production of progeny of F1 adults. The highest repellency (93.30%) of T. castaneum occurred at the highest concentration (5.0% suspension of T. sureni); while the lowest (0.0%) repellency occurred at 0.5% suspension after 1 day of treatment. The highest mortality against adults (86.71%), larvae (88.32%) and pupae (85%) occurred at 5% suspension at 8 days after application. There was a negative correlation between the concentrations of T. sureni and the production of F1 adult's progeny of T. castaneum. The highest number of progeny (147) of T. castaneum occurred in the control at 7 days after treatment; and the lowest number of progeny (43) occurred at 5.0% concentration in 1 day after treatment. The results show that T. sureni is toxic to T. castaneum and has the potential to control all stages of this insect in stored wheat.

Crocidura cossyrensis Contoli, 1989 (Mammalia, Soridiae): karyotype, biochemical genetics and hybridization experiments

Crocidura cossyrensis Contoli, 1989 (Mammalia, Soricidae): karyotype, biochemical genetics and hybridization experiments. - The shrew Crocidura cossyrensis Contoli, 1989 from Pantelleria (I), a Mediterranean island 100 km south of Sicily and 70 km west from Tunisia, was investigated in order to understand its origin and its relationship with C. russula from Tunisia, Morocco and Switzerland. With the exception of a single heterozygote centric fusion, C. cossyrensis had a karyotype identical with that of C russula from Tunisia (2N = 42, NF = 70 to 72), but it differed from C russula from Morocco and Switzerland (2N = 42, NF = 60). The former have 5-6 pairs of chromosomes with small arms that are acrocentric in the latter. Genetic comparisons with allozyme data revealed small genetic distance (0.04) between C cossyrensis and C russula from Tunisia. In contrast, this eastern clade (Tunisia and Pantelleria) is separated from the western clade (Switzerland and Morocco) by a genetic distance of 0.14. A hybridization experiment between shrews from Pantelleria and Switzerland lead rapidly to an F1 generation. From 12 F1 hybrids that were backcrossed, females reproduced normally, but none of the males did so. Concluding from the results, C. cossyrensis from Pantelleria and C. russula cf. agilis from Tunisia belong to the same taxon that may have reached the differentiation of a biological species within the C. russula group. More geographic samples are needed to determine the definitive taxonomic positions of these shrews.

An observational study of the 7 September 2005 Barcelona tornado outbreak

This paper presents an observational study of the tornado outbreak that took place on the 7 September 2005 in the Llobregat delta river, affecting a densely populated and urbanised area and the Barcelona International airport (NE Spain). The site survey confirmed at least five short-lived tornadoes. Four of them were weak (F0, F1) and the other one was significant (F2 on the Fujita scale). They started mostly as waterspouts and moved later inland causing extensive damage estimated in 9 million Euros, three injured people but fortunately no fatalities. Large scale forcing was provided by upper level diffluence and low level warm air advection. Satellite and weather radar images revealed the development of the cells that spawned the waterspouts along a mesoscale convergence line in a highly sheared and relatively low buoyant environment. Further analysis indicated characteristics that could be attributed indistinctively to non-supercell or to mini-supercell thunderstorms.

Distribuição do amônio, nitrato, potássio e fósforo em colunas de latossolos fertirrigadas

Na fertirrigação, é conveniente aplicar os nutrientes de forma a conseguir sua localização na profundidade mais adequada para absorção por parte das culturas: em maior profundidadepara a cultura perene e, mais superficialmente, nas culturas de ciclo curto. Com os objetivos de estabelecer em que fração da lâmina de irrigação devem ser aplicada as doses de N (NH4+ e NO3-); K+ e H2PO4-, de investigar qual o melhor fracionamento de suas doses, de modo a localizá-los na profundidade adequada, e de determinar a distribuição na coluna de NH4+, NO3-, K+ e H2PO4- aplicados por fertirrigação, foi realizado um experimento em laboratório, utilizando colunas de percolação. Os tratamentos corresponderam a um fatorial 4 (1 + 7), sendo quatro Latossolos de Minas Gerais [dois Latossolos Vermelho-Amarelos distróficos (LVAd1 e LVAd2), um Latossolo Vermelho distroférrico (LVdf) e um Latossolo Vermelho distrófico (LVd)], uma testemunha (aplicação de água deionizada) e sete formas de aplicação de 1 mmol dm-3 de NH4+, 1 mmol dm-3 de NO3-, 2 mmol dm-3 de K+ e 0,667 mmol dm-3 de H2PO4-. A lâmina de água foi dividida em cinco frações iguais (F1 a F5) e a dose dos nutrientes aplicada integralmente (D), ou fracionada em duas (D1/2) ou em três vezes (D1/3). Assim, a aplicação dos nutrientes foi feita segundo o esquema: F2D, F3D, F4D, F2D1/2F3D1/2 , F3D1/2F4D 1/2, F2D1/2F4D1/2 ou F2D1/3F3D1/3 F4D1/3. Subamostras foram utilizadas na análise de NH4+; NO3-; K+ e H2PO4-, determinando-se a distribuição desses nutrientes na coluna de solo. A mobilidade apresentou a seguinte ordem nos solos LVAd1, LVAd2 e LVd: NO3- > NH4+ > K+ > H2PO4-. Já para o solo LVdf, a ordem foi NH4+ > NO3- > K+ > H2PO4-. A ordem de risco de contaminação de águas subterrâneas por NO3- foi a seguinte: LVAd1 > LVAd2 > LVdf > LVd. A quantidade de água acrescentada a cada coluna, inferior a meio volume de poros, não foi suficiente para deslocar o H2PO4- além do primeiro anel. Para os outros íons em estudo, a localização em maior profundidade, quando aplicados como pulso único, foi verificada com a maior concentração no pulso (D > D1/2 > D 1/3) e com a maior lâmina de água posterior à sua aplicação (F2D > F3D > F 4D e F2D1/2F3D1/2 > F3D1/2F4D1/2 ). Os resultados evidenciam que a mobilidade diferencial de N (NH4+ e NO3-) e K+ exigiria escolha cuidadosa das doses desses nutrientes na solução, a fim de evitar perdas de N (NH4+ e NO3-) por lixiviação, ou localização excessivamente superficial do K+. A baixa mobilidade do H2PO4- mostra que a fertirrigação não seria uma técnica apropriada para sua incorporação no perfil do solo, visando à fertilização das culturas.

Frações oxidáveis do carbono orgânico em argissolo vermelho-amarelo sob sistema de aleias

O aporte de matéria orgânica ao solo via leguminosas em sistemas de aleias pode ser uma alternativa para o uso sustentável do trópico úmido. O objetivo deste trabalho foi comparar o aporte de matéria orgânica facilmente oxidável proveniente da combinação de resíduos de diferentes leguminosas utilizadas em sistemas de condução de culturas em aleias sob Argissolo Vermelho-Amarelo. Foram avaliadas duas espécies de leguminosas de alta qualidade de resíduos - leucena (Leucaena leucocephala) e guandu (Cajanus cajan), e duas espécies de baixa qualidade de resíduos - sombreiro (Clitoria fairchildiana) e acácia (Acacia mangium), combinadas entre si, nos seguintes tratamentos: sombreiro + guandu; leucena + guandu; acácia + guandu; sombreiro + leucena; leucena + acácia e testemunha sem leguminosa. As amostras de solo foram coletadas nas profundidades de 0-5 e 5-10 cm, nas entrelinhas. Foi quantificado e fracionado o C orgânico total (COT), estratificado em quatro frações (F1, F2, F3 e F4) com graus decrescentes de oxidação. As áreas com sombreiro/leucena, acácia/leucena e acácia/guandu apresentaram os maiores teores de COT (0-5 cm), e a área testemunha, os menores (5-10 cm). A maior proporção do COT estava nas frações F1+F2; a área testemunha teve os menores teores de C nessas frações. O tratamento acácia/guandu apresentou maiores teores de C na fração F1 nas duas profundidades. O tratamento leucena/guandu apresentou as maiores proporções do COT nas frações F3 + F4. Os resultados indicam que, no cultivo em sistema de aleias, a combinação de leguminosas de alta e baixa qualidade de resíduos (acácia/guandu) favorece o aumento de matéria orgânica facilmente decomponível, enquanto o uso de leguminosas de alta qualidade de resíduos favorece maiores proporções de C somente nas frações mais resistentes (F3 + F4).

Geoquímica de radionuclídeos naturais em solos de áreas circunvizinhas a uma Unidade de Mineração e Atividade de Urânio

Os impactos ambientais advindos da exploração e do beneficiamento de U são, em grande parte, idênticos àqueles causados por atividades minero-extrativistas em geral. Este trabalho teve o objetivo de determinar a partição geoquímica dos radionuclídeos naturais 238U, 226Ra e 210Pb em áreas circunvizinhas à Unidade de Mineração e Atividade de Urânio (URA) das Indústrias Nucleares do Brasil S.A., localizada na Província Uranífera de Lagoa Real, no município de Caetité, na região sudoeste do Estado da Bahia. Foram coletadas amostras de solo em cinco áreas circunvizinhas à URA, representando as principais classes de solos da região, na profundidade de 0-20 cm. Nas cinco áreas, foram determinados o teor de atividade total e o fracionamento geoquímico nas frações: F1 - levemente ácida, F2 - reduzível, F3 - oxidável, F4 - alcalina e F5 - residual. As atividades totais médias foram, em Bq kg-1 de solo, de 50 para 238U, 51 para 226Ra e 159 para 210Pb. Os extraídos na fase potencialmente biodisponível (F1) foram: 11 % para 238U, 13 % para 226Ra e 3 % para 210Pb. O 238U apresentou maior biodisponibilidade nos solos mais ácidos e maior afinidade pelos óxidos de Fe, o que não ocorreu para o 226Ra, tendo este apresentado a maior biodisponibilidade. O 210Pb apresentouse predominantemente associado a F5. As percentagens elevadas de 238U, 226Ra e 210Pb na fração geoquímica F5 indicam que as atividades observadas nos cinco solos estão, predominantemente, associadas ao material que deu origem a esses solos, e não a um processo de contaminação artificial em função da atividade da URA.

Lymphocyte specificity to protein antigens. V. Conformational dependence of activation of cytochrome c-specific T cells.

Variations in the immunogenic and antigenic properties of native and denatured forms of cytochrome c were observed depending on the strain of mouse tested. In C57BL/6 and (C57BL/6 X DBA/2)F1 (BDF1) mice, priming with either native or denatured cytochrome c (apocytochrome c) gave rise to T cell blasts responding in a similar fashion to the two forms of the antigen and to different peptides derived from CNBr cleavage of the protein when tested for proliferation in the presence of C57BL/6 or BDF1 accessory cells. A different pattern of proliferation was observed when apocytochrome c-specific DBA/2 or BDF1 T cell blasts were tested with DBA/2 accessory cells. In this case, no response was obtained to heme peptide 1-65. This was not due to an inability of DBA/2 macrophages to process and present heme peptide 1-65, as they were able to present this antigen to native cytochrome c-specific BDF1 T cell blasts. Thus, it seems that different sets of clones are generated upon priming BDF1 mice with denatured cytochrome c which are able to recognize different sets of peptides depending on the nature of the accessory cells. The results obtained are consistent with the hypothesis that degradation and presentation of native and denatured cytochrome c by macrophages is dependent on the three-dimensional conformation of the protein.