Glycoprotein VI is a major collagen receptor for platelet activation: it recognizes the platelet-activating quaternary structure of collagen, whereas CD36, glycoprotein IIb/IIIa, and von Willebrand factor do not

Simple collagen-related peptides (CRPs) containing a repeat Gly-Pro-Hyp sequence are highly potent platelet agonists. Like collagen, they must exhibit tertiary (triple-helical) and quaternary (polymeric) structure to activate platelets. Platelet signaling events induced by the peptides are the same as most of those induced by collagen. The peptides do not recognize the alpha 2 beta 1 integrin. To identify the signaling receptor involved, we have evaluated the response to the CRP, Gly-Lys-Hyp(Gly-Pro-Hyp)10-Gly-Lys-Hyp-Gly of platelets with defined functional deficiencies. These studies exclude a primary recognition role for CD36, von Willebrand factor (vWF), or glycoprotein (GP) IIb/IIIa. Thus, both CD36 and vWF-deficient platelets exhibited normal aggregation, normal fibrinogen binding, and normal expression of CD62 and CD63, measured by flow cytometry, in response to the peptide, and there was normal expression of CD62 and CD63 on thrombasthenic platelets. In contrast, GPVI-deficient platelets were totally unresponsive to the peptide, indicating that this receptor recognizes the Gly-Pro-Hyp sequence in collagen. GPVI-deficient platelets showed some fibrinogen binding in response to collagen but failed to aggregate and to express CD62 and CD63. Collagen, but not CRP-XL, contains binding sites for alpha 2 beta 1. Therefore, it is possible that collagen still induces some signaling via alpha 2 beta 1, leading to activation of GPIIb/IIIa. Our findings are consistent with a two-site, two-step model of collagen interaction with platelets involving recognition of specific sequences in collagen by an adhesive receptor such as alpha 2 beta 1 to arrest platelets under flow and subsequent recognition of another specific collagen sequence by an activatory receptor, namely GPVI.

Structure-function relation in retinoid regulated gene expression

Retinoids are known to inhibit proliferation of and induce terminal differentiation of many normal and transformed cells. It has been postulated that retinoids exert their effect by altering gene expression. HL-60 cells and macrophages both respond to retinoic acid action by the rapid induction of the enzyme tissue transglutaminase. The induction has been shown to be due to increased transcription of the transglutaminase gene. The first part of the dissertation studied the structure-function relationship of retinoid-regulated transglutaminase induction, differentiation and proliferation in HL-60 cells using retinoid analogs. The results indicated strict structural constraints and a strong structure-function correlation between transglutaminase induction and differentiation; those retinoids that induced transglutaminase also induced differentiation, those analogs that did not induce transglutaminase could not induce differentiation. The ability of the retinoids to induce transglutaminase in HL-60 cells was paralleled in macrophages. However, the antiproliferative effect of the retinoids displayed less stringent structural constraints than their differentiation- and transglutaminase-inducing properties. Specifically all the retinoids were able to inhibit proliferation to varying extents. It is concluded that the induction of transglutaminase and of differentiation by retinoids is mediated by receptors. While receptor mediation cannot be entirely ruled out, with the current data no definitive statement can be made about the antiproliferative activity of retinoids. Also, the concordance in the ability of the retinoids to induce transglutaminase and the ability to induce differentiation of HL-60 cells suggests that the former is an early response of the cells to retinoids and differentiation a later consequence on the same pathway. Using the induction of transglutaminase as an index of the direct, or primary, effect of retinoids on gene expression, the second part of the dissertation investigates, by 2D gel electrophoresis, the alteration in the rates of synthesis of other proteins in macrophages and HL-60 cells in response to short incubations with retinoic acid. Any changes in parallel with transglutaminase were taken to indicate proteins directly under the control of retinoic acid. It is concluded that retinoic acid regulates the expression of a circumscribed set of genes in a cell-specific manner. The results support the hypothesis that retinoids exert their multiple effects on myeloid cells, in part, by receptor-mediated alternations in gene expression. ^

Human TNF receptor p75/80 gene structure and promoter characterization

Tumor necrosis factor receptor p75/80 ((TNF-R p75/80) is a 75 kDa type 1 transmembrane protein expressed predominately on cells of hematopoietic lineage. TNF-R p75/80 belongs to the TNF receptor superfamily characterized by cysteine-rich extracellular regions composed of three to six disulfide-linked domains. In the present report, we have characterized, for the first time, the complete gene structure for human TNF-R p75/80 which spans approximately 43 kbp. The gene consists of 10 exons (ranging from 34 bp to 2.5 kbp) and 9 introns (343 bp to 19 kbp). Consensus elements for transcription factors involved in T cell development and activation were noted in the 5$\sp\prime$ flanking region including TCF-1, Ikaros, AP-1, CK-2, IL-6RE, ISRE, GAS, NF-$\kappa$B and SP1, as well as an unusually high GC content and CpG frequency that appears characteristic of some TNF-R family members. The unusual (GATA)$\sb{\rm n}$ and (GAA)(GGA) repeats found within intron 1 may prove useful for further genome analysis within the 1p36 chromosomal locus. The human TNF-R p75/80 gene structure will permit further assessment of its involvement in normal hematopoietic cell development and function, autoimmune disease, and non-random translocations in hematopoietic malignancies. The region 1.8 kb 5$\sp\prime$ of the ATG was able to drive luciferase expression when transfected into cell lines expressing TNF-R p75/80. Further characterization of the 5$\sp\prime$-regulatory region will aid in determining factors and signal transduction pathways involved in regulating TNF-R p75/80 expression. ^

Effects of anticancer drug docetaxel on the structure and function of the rabbit olfactory mucosa

Docetaxel (DCT) is an anticancer drug which acts by disrupting microtubule dynamics in the highly mitotic cancer cells. Thus, this drug has a potential to affect function and organization of tissues exhibiting high cellular turnover. We investigated, in the rabbit, the effects of a single human equivalent dose (6.26mg/kg, i.v.) of DCT on the olfactory mucosa (OM) through light and electron microscopy, morphometry, Ki-67 immunostaining, TUNEL assay and the buried food test for olfactory sensitivity. On post-exposure days (PED) 5 and 10, there was disarrangement of the normal cell layering in the olfactory epithelium (OE), apoptotic death of cells of the OE, Bowman's glands and axon bundles, and the presence (including on PED 3) of blood vessels in the bundle cores. A decrease in bundle diameters, olfactory cell densities and cilia numbers, which was most significant on PED 10 (49.3%, 63.4% and 50%, respectively), was also evident. Surprisingly by PED 15, the OM regained normal morphology. Furthermore, olfactory sensitivity decreased progressively until PED 10 when olfaction was markedly impaired, and with recovery from the impairment by PED 15. These observations show that DCT transiently alters the structure and function of the OM suggesting a high regenerative potential for this tissue.

Effects of microbeam radiation therapy on normal and tumoral blood vessels

Microbeam radiation therapy (MRT) is a new form of preclinical radiotherapy using quasi-parallel arrays of synchrotron X-ray microbeams. While the deposition of several hundred Grays in the microbeam paths, the normal brain tissues presents a high tolerance which is accompanied by the permanence of apparently normal vessels. Conversely, the efficiency of MRT on tumor growth control is thought to be related to a preferential damaging of tumor blood vessels. The high resistance of the healthy vascular network was demonstrated in different animal models by in vivo biphoton microscopy, magnetic resonance imaging, and histological studies. While a transient increase in permeability was shown, the structure of the vessels remained intact. The use of a chick chorioallantoic membrane at different stages of development showed that the damages induced by microbeams depend on vessel maturation. In vivo and ultrastructural observations showed negligible effects of microbeams on the mature vasculature at late stages of development; nevertheless a complete destruction of the immature capillary plexus was found in the microbeam paths. The use of MRT in rodent models revealed a preferential effect on tumor vessels. Although no major modification was observed in the vasculature of normal brain tissue, tumors showed a denudation of capillaries accompanied by transient increased permeability followed by reduced tumor perfusion and finally, a decrease in number of tumor vessels. Thus, MRT is a very promising treatment strategy with pronounced tumor control effects most likely based on the anti-vascular effects of MRT.

The characterization of mouse carboxypeptidase N small subunit gene structure and presence in developing embryos

Carboxypeptidase N (CPN) is a plasma zinc metalloprotease, which consists of two enzymatically active small subunits and two large subunits that protect the protein from degradation. CPN cleaves carboxy-terminal arginines and lysines from peptides found in the bloodstream such as complement anaphylatoxins, kinins, and creatine kinase MM. In this study, the mouse CPN small subunit (CPN1) coding region, gene structure, and chromosomal location were characterized and the expression of CPN1 was investigated in mouse embryos at different stages of development. The CPN1 gene, which was approximately 29 kb in length, contained nine exons and localized to mouse chromosome 19D2. The fifth and sixth exons of CPN1 encoded the amino acids necessary for substrate binding and catalytic activity. CPN1 RNA was expressed predominately in adult liver and contained a 1371 bp open reading frame encoding 457 amino acids. In the mouse embryo, CPN1 RNA was observed at 8.5 days post coitus (dpc), while its protein was detected at 10.5 dpc. In situ hybridization of the fetal liver detected CPN1 RNA in erythroid progenitor cells at 10.5, 13.5, and 16.5 dpc and in hepatocytes at 16.5 dpc. This was compared to the expression of the complement component C3, the parent molecule of complement anaphylatoxin C3a. Consistently throughout the experiments, CPN1 message and protein preceded the expression of C3. To obtain a better understanding of the biological significance of CPN1 in vivo, studies were initiated to produce a genetically engineered mouse in which the CPN1 gene was ablated. To facilitate this project a targeting vector was constructed by removing the functionally important fifth and sixth exons of the CPN1 gene. Collectively, these studies have: (1) provided important detailed information regarding the structure and organization of the murine CPN1 gene, (2) yielded insights into the developmental expression of mouse CPN1 in relationship to C3 expression, and (3) set the stage for the generation of a CPN1 “knock-out” mouse, which can be used to determine the biological significance of CPN1 in both normal and diseased conditions. ^

Tranversal motion and flow structure of fully nonlinear streaks in a laminar boundary layer

Typical streak computations present in the literature correspond to linear streaks or to small amplitude nonlinear streaks computed using DNS or nonlinear PSE. We use the Reduced Navier-Stokes (RNS) equations to compute the streamwise evolution of fully non-linear streaks with high amplitude in a laminar flat plate boundary layer. The RNS formulation provides Reynolds number independent solutions that are asymptotically exact in the limit $Re \gg 1$, it requires much less computational effort than DNS, and it does not have the consistency and convergence problems of the PSE. We present various streak computations to show that the flow configuration changes substantially when the amplitude of the streaks grows and the nonlinear effects come into play. The transversal motion (in the wall normal-streamwise plane) becomes more important and strongly distorts the streamwise velocity profiles, that end up being quite different from those of the linear case. We analyze in detail the resulting flow patterns for the nonlinearly saturated streaks and compare them with available experimental results.

The internal structure of hydrogen-air difussion flames

The Internal Structure of Hydrogen-Air Diffusion Flames. Tho purpose of this paper is to study finite rate chemistry effects in diffusion controlled hydrogenair flames undor conditions appearing in some cases in a supersonic combustor. Since for large reaction rates the flame is close to chemical equilibrium, the reaction takes place in a very thin region, so thata "singular perturbation "treatment" of the problem seems appropriate. It has been shown previously that, within the inner or reaction zone, convection effects may be neglocted, the temperature is constant across the flame, and tho mass fraction distributions are given by ordinary differential equations, whore tho only independent variable involved is tho coordinate normal to the flame surface. Tho solution of the outer problom, which is a pure mixing problem with the additional condition that fuol and oxidizer do not coexist in any zone, provides t h e following information: tho flame position, rates of fuel consumption, temperature, concentrators of species, fluid velocity outside of tho flame, and the boundary conditions required to solve the "inner problem." The main contribution of this paper consists in the introduction of a fairly complicated chemical kinetic scheme representing hydrogen-oxygen reaction. The nonlinear equations expressing the conservation of chemical species are approximately integrated by means of an integral method. It has boen found that, in the case considered of a near-equilibrium diffusion flame, tho role played by the dissociation-recombination reactions is purely marginal, and that somo of the second order "shuffling" reactions are close to equilibrium. The method shown here may be applied to compute the distanco from the injector corresponding to a given separation from equilibrium, say ten to twenty percent. For the casos whore this length is a small fraction of the combustion zone length, the equilibrium treatment describes properly tho flame behavior.

Analysis of the problems associated with dynamic interaction between train, track and structure at transition zones

El gran desarrollo experimentado por la alta velocidad en los principales países de la Unión Europea, en los últimos 30 años, hace que este campo haya sido y aún sea uno de los principales referentes en lo que a investigación se refiere. Por otra parte, la aparición del concepto super − alta velocidad hace que la investigación en el campo de la ingeniería ferroviaria siga adquiriendo importancia en los principales centros de investigación de los países en los que se desea implantar este modo de transporte, o en los que habiendo sido ya implantado, se pretenda mejorar. Las premisas de eficacia, eficiencia, seguridad y confort, que este medio de transporte tiene como razón de ser pueden verse comprometidas por diversos factores. Las zonas de transición, definidas en la ingeniería ferroviaria como aquellas secciones en las que se produce un cambio en las condiciones de soporte de la vía, pueden afectar al normal comportamiento para el que fue diseñada la infraestructura, comprometiendo seriamente los estándares de eficiencia en el tiempo de viaje, confort de los pasajeros y aumentando considerablemente los costes de mantenimiento de la vía, si no se toman las medidas oportunas. En esta tesis se realiza un estudio detallado de la zonas de transición, concretamente de aquellas en las que existe una cambio en la rigidez vertical de la vía debido a la presencia de un marco hidráulico. Para realizar dicho estudio se lleva a cabo un análisis numérico de interacción entre el vehículo y la estructura, con un modelo bidimensional de elemento finitos, calibrado experimentalmente, en estado de tensión plana. En este análisis se tiene en cuenta el efecto de las irregularidades de la vía y el comportamiento mecánico de la interfaz suelo-estructura, con el objetivo de reproducir de la forma más real posible el efecto de interacción entre el vehículo, la vía y la estructura. Otros efectos como la influencia de la velocidad del tren y los asientos diferenciales, debidos a deformaciones por consolidación de los terraplenes a ambos lados el marco hidráulico, son también analizados en este trabajo. En esta tesis, los cálculos de interacción se han llevado a cabo en dos fases diferentes. En la primera, se ha considerado una interacción sencilla debida al paso de un bogie de un tren Eurostar. Los cálculos derivados de esta fase se han denominado cálculos a corto plazo. En la segunda, se ha realizado un análisis considerando múltiples pasos de bogie del tren Eurostar, conformando un análisis de degradación en el que se tiene en cuenta, en cada ciclo, la deformación de la capa de balasto. Los cálculos derivados de esta fase, son denominados en el texto como cálculos a largo plazo. Los resultados analizados muestran que la utilización de los denominados elementos de contacto es fundamental cuando se desea estudiar la influencia de asientos diferenciales, especialmente en transiciones terraplén-estructura en las que la cuña de cimentación no llega hasta la base de cimentación de la estructura. Por otra parte, tener en cuenta los asientos del terraplén, es sumamente importante, cuando se desea realizar un análisis de degradación de la vía ya que su influencia en la interacción entre el vehículo y la vía es muy elevada, especialmente para valores altos de velocidad del tren. En cuanto a la influencia de las irregularidades de la vía, en los cálculos efectuados, se revela que su importancia es muy notable, siendo su influencia muy destacada cuanto mayor sea la velocidad del tren. En este punto cabe destacar la diferencia de resultados derivada de la consideración de perfiles de irregularidades de distinta naturaleza. Los resultados provenientes de considerar perfiles artificiales son en general muy elevados, siendo estos más apropiados para realizar estudios de otra índole, como por ejemplo de seguridad al descarrilamiento. Los resultados provenientes de perfiles reales, dados por diferentes Administradores ferroviarios, presentan resultados menos elevados y más propios del problema analizar. Su influencia en la interacción dinámica entre el vehículo y la vía es muy importante, especialmente para velocidades elevadas del tren. Además el fenómeno de degradación conocido como danza de traviesas, asociado a zonas de transición, es muy susceptible a la consideración de irregularidades de la vía, tal y como se desprende de los cálculos efectuados a largo plazo. The major development experienced by high speed in the main countries of the European Union, in the last 30 years, makes railway research one of the main references in the research field. It should also be mentioned that the emergence of the concept superhigh − speed makes research in the field of Railway Engineering continues to gain importance in major research centers in the countries in which this mode of transportation is already implemented or planned to be implemented. The characteristics that this transport has as rationale such as: effectiveness, efficiency, safety and comfort, may be compromised by several factors. The transition zones are defined in railway engineering as a region in which there is an abrupt change of track stiffness. This stiffness variation can affect the normal behavior for which the infrastructure has been designed, seriously compromising efficiency standards in the travel time, passenger comfort and significantly increasing the costs of track maintenance, if appropriate measures are not taken. In this thesis a detailed study of the transition zones has been performed, particularly of those in which there is a change in vertical stiffness of the track due to the presence of a reinforced concrete culvert. To perform such a study a numerical interaction analysis between the vehicle, the track and the structure has been developed. With this purpose a two-dimensional finite element model, experimentally calibrated, in a state of plane stress, has been used. The implemented numerical models have considered the effects of track irregularities and mechanical behavior of soil-structure interface, with the objective of reproducing as accurately as possible the dynamic interaction between the vehicle the track and the structure. Other effects such as the influence of train speed and differential settlement, due to secondary consolidation of the embankments on both sides of culvert, have also been analyzed. In this work, the interaction analysis has been carried out in two different phases. In the first part a simple interaction due to the passage of a bogie of a Eurostar train has been considered. Calculations derived from this phase have been named short-term analysis. In the second part, a multi-load assessment considering an Eurostar train bogie moving along the transition zone, has been performed. The objective here is to simulate a degradation process in which vertical deformation of the ballast layer was considered. Calculations derived from this phase have been named long-term analysis. The analyzed results show that the use of so-called contact elements is essential when one wants to analyze the influence of differential settlements, especially in embankment-structure transitions in which the wedge-shaped backfill does not reach the foundation base of the structure. Moreover, considering embankment settlement is extremely important when it is desired to perform an analysis of track degradation. In these cases the influence on the interaction behaviour between the vehicle and the track is very high, especially for higher values of speed train. Regarding the influence of the track irregularities, this study has proven that the track’s dynamic response is heavily influenced by the irregularity profile and that this influence is more important for higher train velocities. It should also be noted that the difference in results derived from consideration of irregularities profiles of different nature. The results coming from artificial profiles are generally very high, these might be more appropriate in order to study other effects, such as derailment safety. Results from real profiles, given by the monitoring works of different rail Managers, are softer and they fit better to the context of this thesis. The influence of irregularity profiles on the dynamic interaction between the train and the track is very important, especially for high-speeds of the train. Furthermore, the degradation phenomenon known as hanging sleepers, associated with transition zones, is very susceptible to the consideration of track irregularities, as it can be concluded from the long-term analysis.

The structure of the two amino-terminal domains of human ICAM-1 suggests how it functions as a rhinovirus receptor and as an LFA-1 integrin ligand

The normal function of human intercellular adhesion molecule-1 (ICAM-1) is to provide adhesion between endothelial cells and leukocytes after injury or stress. ICAM-1 binds to leukocyte function-associated antigen (LFA-1) or macrophage-1 antigen (Mac-1). However, ICAM-1 is also used as a receptor by the major group of human rhinoviruses and is a catalyst for the subsequent viral uncoating during cell entry. The three-dimensional atomic structure of the two amino-terminal domains (D1 and D2) of ICAM-1 has been determined to 2.2-Å resolution and fitted into a cryoelectron microscopy reconstruction of a rhinovirus–ICAM-1 complex. Rhinovirus attachment is confined to the BC, CD, DE, and FG loops of the amino-terminal Ig-like domain (D1) at the end distal to the cellular membrane. The loops are considerably different in structure to those of human ICAM-2 or murine ICAM-1, which do not bind rhinoviruses. There are extensive charge interactions between ICAM-1 and human rhinoviruses, which are mostly conserved in both major and minor receptor groups of rhinoviruses. The interaction of ICAMs with LFA-1 is known to be mediated by a divalent cation bound to the insertion (I)-domain on the α chain of LFA-1 and the carboxyl group of a conserved glutamic acid residue on ICAMs. Domain D1 has been docked with the known structure of the I-domain. The resultant model is consistent with mutational data and provides a structural framework for the adhesion between these molecules.

A unified theory of carcinogenesis based on order–disorder transitions in DNA structure as studied in the human ovary and breast

Fourier transform-infrared/statistics models demonstrate that the malignant transformation of morphologically normal human ovarian and breast tissues involves the creation of a high degree of structural modification (disorder) in DNA, before restoration of order in distant metastases. Order–disorder transitions were revealed by methods including principal components analysis of infrared spectra in which DNA samples were represented by points in two-dimensional space. Differences between the geometric sizes of clusters of points and between their locations revealed the magnitude of the order–disorder transitions. Infrared spectra provided evidence for the types of structural changes involved. Normal ovarian DNAs formed a tight cluster comparable to that of normal human blood leukocytes. The DNAs of ovarian primary carcinomas, including those that had given rise to metastases, had a high degree of disorder, whereas the DNAs of distant metastases from ovarian carcinomas were relatively ordered. However, the spectra of the metastases were more diverse than those of normal ovarian DNAs in regions assigned to base vibrations, implying increased genetic changes. DNAs of normal female breasts were substantially disordered (e.g., compared with the human blood leukocytes) as were those of the primary carcinomas, whether or not they had metastasized. The DNAs of distant breast cancer metastases were relatively ordered. These findings evoke a unified theory of carcinogenesis in which the creation of disorder in the DNA structure is an obligatory process followed by the selection of ordered, mutated DNA forms that ultimately give rise to metastases.

The structure and organization within the membrane of the helices composing the pore-forming domain of Bacillus thuringiensis δ-endotoxin are consistent with an “umbrella-like” structure of the pore

The aim of this study was to elucidate the mechanism of membrane insertion and the structural organization of pores formed by Bacillus thuringiensis δ-endotoxin. We determined the relative affinities for membranes of peptides corresponding to the seven helices that compose the toxin pore-forming domain, their modes of membrane interaction, their structures within membranes, and their orientations relative to the membrane normal. In addition, we used resonance energy transfer measurements of all possible combinatorial pairs of membrane-bound helices to map the network of interactions between helices in their membrane-bound state. The interaction of the helices with the bilayer membrane was also probed by a Monte Carlo simulation protocol to determine lowest-energy orientations. Our results are consistent with a situation in which helices α4 and α5 insert into the membrane as a helical hairpin in an antiparallel manner, while the other helices lie on the membrane surface like the ribs of an umbrella (the “umbrella model”). Our results also support the suggestion that α7 may serve as a binding sensor to initiate the structural rearrangement of the pore-forming domain.

Glycosylation differences between the normal and pathogenic prion protein isoforms

Prion protein consists of an ensemble of glycosylated variants or glycoforms. The enzymes that direct oligosaccharide processing, and hence control the glycan profile for any given glycoprotein, are often exquisitely sensitive to other events taking place within the cell in which the glycoprotein is expressed. Alterations in the populations of sugars attached to proteins can reflect changes caused, for example, by developmental processes or by disease. Here we report that normal (PrPC) and pathogenic (PrPSc) prion proteins (PrP) from Syrian hamsters contain the same set of at least 52 bi-, tri-, and tetraantennary N-linked oligosaccharides, although the relative proportions of individual glycans differ. This conservation of structure suggests that the conversion of PrPC into PrPSc is not confined to a subset of PrPs that contain specific sugars. Compared with PrPC, PrPSc contains decreased levels of glycans with bisecting GlcNAc residues and increased levels of tri- and tetraantennary sugars. This change is consistent with a decrease in the activity of N-acetylglucosaminyltransferase III (GnTIII) toward PrPC in cells where PrPSc is formed and argues that, in at least some cells forming PrPSc, the glycosylation machinery has been perturbed. The reduction in GnTIII activity is intriguing both with respect to the pathogenesis of the prion disease and the replication pathway for prions.

A highly digestible sorghum mutant cultivar exhibits a unique folded structure of endosperm protein bodies

The endosperm of a sorghum mutant cultivar, with high in vitro uncooked and cooked protein digestibilities, was examined by transmission electron microscopy and α-, β-, and γ-kafirins (storage proteins) were localized within its protein bodies. Transmission electron microscopy micrographs revealed that these protein bodies had a unique microstructure related to high protein digestibility. They were irregular in shape and had numerous invaginations, often reaching to the central area of the protein body. Protein bodies from normal cultivars, such as P721N studied here, with much lower uncooked and cooked digestibilities are spherical and contain no invaginations. Immunocytochemistry results showed that the relative location of α- and β-kafirins within the protein bodies of the highly digestible genotype were similar to the normal cultivar, P721N. γ-Kafirin, however, was concentrated in dark-staining regions at the base of the folds instead of at the protein body periphery, as is typical of normal cultivars. The resulting easy accessibility of digestive enzymes to α-kafirin, the major storage protein, in addition to the increased surface area of the protein bodies of the highly digestible cultivar appear to account for its high in vitro protein digestibility.