Biomedical subjects

N Boisset

Publications and source records attributed to N Boisset.

At least 19 recordsLinked to original sources

PubMed2001

Innervation of the caudal denervated ventral roots and their target muscles by the rostral spinal motoneurons after implanting a nerve autograft in spinal cord-injured adult marmosets.

OBJECT: The authors conducted a study to determine the effects of using a nerve autograft (NAG) to promote and guide axonal regrowth from the rostral spinal cord to the caudal lumbar ventral nerve roots to restore hindlimb motor function in adult marmosets after lower thoracic cord injury. METHODS: Nine animals underwent a left-sided hemisection of the spinal cord at T-12 via left-sided T9-L3 hemilaminectomy, with section of all ipsilateral lumbrosacral ventral nerve roots. In the experimental group (five animals), an NAG obtained from the right peroneal nerve was anastomosed with the sectioned and electrophysiologically selected lumbar ventral roots (left L-3 and L-4) controlling the left quadriceps muscle and then implanted into the left ventrolateral T-10 cord. In the control group (four animals), the sectioned/selected lumbar ventral roots were only ligated. After surgery, all marmosets immediately suffered from complete paralysis of their left hindlimb. Five months later, some clinical signs of reinnervation such as tension and resistance began to appear in the paralyzed quadriceps of all experimental animals that received autografts. Nine months postoperatively, three of the five experimental marmosets could maintain their lesioned hindlimb in hip flexion. Muscle action potentials and motor evoked potentials were recorded from the target quadriceps in all experimental marmosets, but these potentials were absent in the control animals. Horseradish peroxidase retrograde labeling from the distal sectioned/reconnected lumbar ventral roots traced 234+/-178 labeled neurons in the ipsilateral T8-10 ventral horn, mainly close to the NAG tip. Histological analysis showed numerous regenerating axons in this denervated/reconnected nerve root pathway, as well as newly formed motor endplates in the denervated/reinnervated quadriceps. No axonal regeneration was detected in the control animals. CONCLUSIONS: These data indicate that the rostral spinal neurons can regrow into the caudal ventral roots through an NAG, thereby innervating the target muscle in adult marmosets after spinal cord injury.

Animals↗

PubMed2000

Sepia officinalis hemocyanin: A refined 3D structure from field emission gun cryoelectron microscopy.

The extracellular respiratory pigment of the cuttlefish Sepia officinalis was observed by cryoelectron microscopy with conventional LaB(6) and field emission gun electron sources at 100 and 200 kV, respectively. Each image series was used to compute one 3D reconstruction volume with correction of the contrast transfer function by Wiener filtering. A strong boosting of the contrast was corrected by band-pass filtering of the final volumes, and a qualitative gain in resolution was observed when using the field emission gun electron microscope. In this volume, a strong signal is present down to 1/18 A(-1) and some meaningful information is obtained down to 1/12.5 A(-1). The complex is composed of five pairs of polypeptide chains and resembles a hollow cylinder with five wall oblique units and five inner arches. Three types of wall-wall connections termed pillar P1 to P3 are visible in this volume and the four functional units present in the arches are each linked to the wall by two arch-wall connections. The dispositions of the functional units in the arches of Sepia and Octopus hemocyanins share no common feature.

Animals↗

PubMed2000

[Horseradish peroxidase retrograde labeling of primary sensory axons in rats: a comparison between three different intraspinal injections methods].

STUDY AIM: In order to improve the results of intraspinal retrograde labeling of post-ganglionic primary sensory axons by horseradish peroxidase (HRP), the authors compared three different intraspinal injection methods of this tracer into the inferior thoracic spinal cord in the rat. MATERIAL AND METHOD: 'Open field' method (group 1, N = 8); stereotactic injection, needle tip diameter = 0.72 mm (group 2, N = 8); stereotactic injection, needle tip diameter = 0.24 mm (group 3, N = 8). Histological features of the spinal injection site showed that tissue damages due to injection was more extensive and deeper than expected. HRP transported in retrograde fashion from injection site to sensory body cells located in dorsal root ganglia (DRG) was revealed by the Mesulam histochemical technique. RESULTS: The mean number of labeled neurons per DRG was 652 in group 3, 116 in group 2, and 77 in group 1. Differences were statistically significant, especially between groups 1 and 3 (P = 4.10(-16)) and groups 2 and 3 (P = 2.10(-17)). CONCLUSION: Retrograde labeling of primary sensory axons by HRP (or another axonal tracer) with fine needle stereotactic intraspinal injection may represent an alternative to anterograde labeling. This reliable and reproducible method may be useful in studies dealing with regeneration of post-ganglionic primary sensory axons.

Animals↗

PubMed1999

Three-dimensional reconstruction of Lumbricus terrestris hemoglobin at 22 A resolution: intramolecular localization of the globin and linker chains.

A 3D reconstruction of the hemoglobin (Hb) of the earthworm Lumbricus terrestris was carried out by the 3D projection alignment method from electron microscopy images of a frozen-hydrated specimen at 22 A resolution. The results were analyzed by a new approach taking into account the evolution of the 210 densities forming the 3D volume as a function of the threshold of surface representation. The whole oligomer with D6point-group symmetry is comprised of 12 hollow globular substructures (HGS) with local 3-fold symmetry tethered to a complex network of linking subunits (linker complex). The 12 globin subunits of each HGS are distributed around local 3-fold axis in four layers of three subunits. The first layer, the most external, contains monomeric globin chains 2A, 3A, and 5A. The three trimers corresponding to the nine remaining subunits have one subunit in each of the second (2B, 3B, 5B), third (1A, 4A, 6A), and fourth (1B, 4B, 6B) layer. The distances between the centers of the globin chains forming the trimers are in the ranges 20-32 A and 45-52 A. The linker complex is made up of two types of linking units. The first type forms three loops connecting globin chains of the second, third and fourth layers. The average molecular mass (Mm) of these subunits was 25 kDa. The second type forms the central structure, termed hexagonal toroid, and its 12 connections to the HGS. This structure corresponds to a hexamer of a single linking unit with a Mm (31.2 kDa), size and a shape different from those of the HGS loops. A careful study of 3D volume architecture shows that each toroid linking unit is bound to the three loops of a HGS pair located in the upper and lower hexagonal layers, respectively. As shown in a model of architecture, hexagonal bilayered (HBL) Hbs can be built very simply from 144 globin chains and 42 linker chains belonging to two different types. We also propose a simple assembly sequence for the construction of HBL Hbs based on the architecture model.

Animals↗

PubMed1999

Reinnervation of denervated lumbar ventral roots and their target muscle by thoracic spinal motoneurons via an implanted nerve autograft in adult rats after spinal cord injury.

Intraspinally implanting a nerve autograft (NAG) to promote axonal regeneration toward periphery was investigated as a surgical treatment for spinal cord injury in adult rats. Fifteen animals underwent a left hemisection of the spinal cord at T12 level and an intradural section of all ipsilateral lumbar ventral roots. In repaired animals (n = 9), the electrophysiologically selected left L3 and L4 lumbar ventral roots supplying the quadriceps muscle were anastomosed to a NAG. The NAG was taken from the right peroneal nerve and then ventrolaterally implanted into the cord at a level 7 mm rostral to the hemisection. In the control group (n = 6), sectioned lumbar ventral roots were left unrepaired. Nine months later, the animals were assessed with clinical, electrophysiological, and histological examinations. Muscle action potential and motor evoked potential were obtained from the denervated/reinnervated quadriceps in all repaired animals, with a mean amplitude of 918.3+/-328.9 microV and 215.8+/-39.7 microV, respectively. Horseradish peroxidase retrograde labeling from the denervated/repaired lumbar ventral roots, performed in five repaired animals, showed that the mean of labeled neurons, ipsilaterally located in the thoracic ventral horn near the implantation site, was 145.8+/-111.7. Histological analysis showed numerous myelinated axons in the NAG and denervated/repaired lumbar ventral roots of all repaired animals. The study of neuromuscular junctions furthermore confirmed numerous newly formed endplates appearing in the denervated/reinnervated quadriceps. These changes were absent in the control animals. These data indicate that the rostral thoracic spinal motoneurons can innervate the caudal denervated/repaired lumbar ventral roots and the target quadriceps via an implanted NAG, thereby inducing some functional recovery in adult rats after lower thoracic spinal cord injury.

Action Potentials↗

PubMed1999

Structural comparison of cephalopod hemocyanins: phylogenetic significance.

Hemocyanins, the respiratory molecules of cephalopod mollusks, are hollow cylinders with five internal arches. Three hemocyanins representative of three orders of cephalopods (Benthoctopus species, Octopoda; Vampyroteuthis infernalis, Vampyromorpha; Sepia officinalis, Sepioidea) were subjected to cryoelectron microscopy and three-dimensional (3D) reconstruction. The structure of Benthoctopus hemocyanin, solved at 26.4-A resolution, possesses arches comprising two identical functional units. The similarity between these functional units and the structure recently observed in X-ray crystallography for Octopus by Cuff et al. (J. Mol. Biol., 1998, 232, 522-529) allows the identification of their N- and C-terminal domains in the 3D reconstruction volume. Conversely, arches present in the 3D reconstruction volume of Sepia hemocyanin (21.8 A resolution) contain four functional units that are disposed differently. The strong resemblance between the reconstruction volumes of Vampyroteuthis (21.4-A resolution) and Benthoctopus hemocyanins suggests that Sepioidea diverged from a group containing Octopoda and Vampyromorpha.

Animals↗

PubMed1998

Intramolecular localization of the functional units of Sepia officinalis hemocyanin by immunoelectron microscopy.

The quaternary structure of Sepia officinalis hemocyanin (Hc) as studied in immunoelectron microscopy with rabbit IgGs and Fab fragments raised against functional units (FU) Soc, Sod, Soe, Sof, Sog, and Soh and fragment Soab. The architecture of immunocomplexes shows that (i) epitopes characteristic of FUs Soc and Sog and of fragment Soab are located in the two external tiers of FUs, (ii) FUs Soh and Soe or Sod are located in arches. These results were confirmed using immunocomplexes made up of Sepia Hc and IgGs or Fab fragments purified from antisera raised against FUs of Octopus vulgaris and Octopus dofleini. Frozen-hydrated immunocomplexes containing one Hc molecule and at least one FU-specific Fab fragment were observed in the electron microscope and submitted to image processing. When the Hc molecule is viewed along its 5-fold axis (i) anti-Soc Fab fragments project on a radius passing through the arch's pillar, (ii) anti-Sof Fabs project slightly out of the arches, and (iii) anti-Soh Fabs project between neighboring arches. When applied to a recent three-dimensional (3D) reconstruction volume, these results allow us to deduce the intramolecular location of five of the eight FUs. For the last three FUs limited uncertainties remain: (i) Soc can be located in two positions in the external tier of FUs; (ii) Soa and Sob can both occupy three positions in the external tiers; and (iii) because of an immunological cross-reactivity Sod may be located in the wall and Soe in the arch, or vice versa. An analysis of the quaternary structure considering the possible locations of the 80 FUs and postulating a single type of subunit shows that 80 possibilities of paths still exist for the polypeptide chain. To solve definitely these 80 possibilities only five questions remain to be answered.

Animals↗

PubMed1998

Axonal regrowth through a collagen guidance channel bridging spinal cord to the avulsed C6 roots: functional recovery in primates with brachial plexus injury.

Intraspinal implantation of a collagen guidance channel (CGC) to promote axon regeneration was investigated in marmosets with brachial plexus injury. After avulsion of the right C5, C6 and C7 spinal roots, a CGC containing (group B) or not (group A) a nerve segment, or a nerve graft (group C), was ventro-laterally implanted into the cord to bridge the ventral horn and the avulsed C6 roots. No spinal cord dysfunction was observed following surgery. Two months later, the postoperative flaccid paralysis of the lesioned arm improved. In five months, a normal electromyogram of the affected biceps muscle was recorded in all repaired animals. Motor evoked potentials were obtained with a mean amplitude of 13.37 +/- 13.66 microV in group A, 13.21 +/- 5.16 microV in group B and 37.14 +/- 35.16 microV in group C. The force of biceps muscle contraction was 27.33 +/- 20.03 g (group A), 24.33 +/- 17.03 g (group B) and 37.38 +/- 21.70 g (group C). Retrograde tracing by horseradish peroxidase showed labelled motoneurons ipsilaterally located in the C5 and C6 ventral horn, nearby the implantation site. The mean labelled neurons was 32.33 +/- 21.13, 219.33 +/- 176.29 and 64.33 +/- 23.54 in group A, B and C respectively. Histological analysis presented numerous myelinated and unmyelinated regenerating axons in the implant of these animals. Statistical analysis did not show significant difference among the three repaired groups. Our results indicate that spinal neurons can regenerate through a CGC to avulsed nerve roots and induce motor recovery in primates.

Animals↗

PubMed1997

Strong expression of GFAP mRNA in rat hippocampus after a closed-head injury.

We investigated the spatiotemporal GFAP mRNA expression over a period of 11 days following brain injury in rats caused by impact acceleration, which is known to produce diffuse axonal injury (DAI). We observed widespread GFAP mRNA expression throughout the brain, which was more rapid and intense in the hippocampus. This expression was obvious in most animals 2 days after injury and appeared maximal at day 6. Although it decreased by day 11, the level of expression remained high compared with control levels. We noted slight differences in time of onset and the magnitude of the response between hippocampus and white matter structures or cortical areas. The different mechanisms able to trigger this response are discussed in regard to histopathological changes observed in DAI models.

Analysis of Variance↗

PubMed1997

Axonal regrowth through collagen tubes bridging the spinal cord to nerve roots.

The capacity of central nervous system (CNS) axons to elongate from the spinal cord to the periphery throughout a tubular implant joining the ventral horn of the spinal cord to an avulsed root was investigated in a model of brachial plexus injury. The C5-C7 roots were avulsed by controlled traction and the C6 root was bridged to the spinal cord over a 3 mm gap by the use of a collagen cylinder containing or not containing an autologous nerve segment, or an autologous nerve graft. Nine months later, the functionality and the quality of the axonal regrowth was evaluated by electrophysiology, retrograde labelling of neurons, and histological examination of the gap area. A normal electromyogram of the biceps was observed in all animals where the C6 root was bridged to the spinal cord. The mean average amplitude of the motor evoked potentials was comprised between 17.51 +/- 12.03 microV in animals repaired with a collagen cylinder, and 27.83 +/- 22.62 microV when a nerve segment was introduced in the tube. In nonrepaired animals spontaneous potentials reflecting a muscle denervation were observed at electromyography. Retrograde labelling indicated that a mean number of 58.88 +/- 37.89 spinal cord neurons have reinnervated the biceps in animals repaired with a tube versus 78.38 +/- 62.11 when a nerve segment was introduced in the channel, and 97.25 +/- 56.23 in nerve grafting experiments. Analyses of the repair site showed the presence of numerous myelinated regenerating axons. In conclusion, our results indicate that spinal cord neurons can regenerate through tubular implants over a 3 mm gap, and that this axonal regrowth appeared as effective as in nerve grafting experiments. The combination of an implant and a nerve segment did not significantly increase the regeneration rate.

Animals↗

PubMed1997

Three-dimensional reconstruction of native and reassembled Lumbricus terrestris extracellular hemoglobin. Localization of the monomeric globin chains.

The approximately 3.5 MDa hexagonal bilayer (HBL) hemoglobin (Hb) of the earthworm Lumbricus terrestris is composed of monomers and disulfide-bonded trimers (T) of globin chains and of four types of heme-deficient linker chains (L). Cryoelectron microscopic images of native Hb and of HBL reassembled from the constituent subunits depleted in monomer subunit (HBL[T+L]) were subjected to three-dimensional reconstructions by the random conical tilt series method. Native Hb has an architecture very similar to those of other annelid and vestimentiferan Hbs, consisting of 12 hollow globular substructures (HGS). Each HGS is comprised of six dense masses, has a 3-fold symmetry, and is organized in two hexagonally symmetric layers, with the vertices of the upper layer rotated 16 degrees clockwise relative to those of the lower layer. The layers are tethered to a central linker complex, consisting of two bracelets of connections perpendicular to the 6-fold axis and a set of six vertical connections linked to a flat hexagonal mass. HBL[T+L] shared all these features with the native Hb, except for a large hole around the 3-fold symmetry axis in each HGS, indicating the probable location of the missing monomer subunit.

Animals↗

PubMed1997

Three-dimensional reconstruction of Limulus polyphemus hemocyanin from cryoelectron microscopy.

Hemocyanin (Hc) the respiratory pigment of the horseshoe crab Limulus polyphemus (Lp) is composed of 48 approximately 75 kDa copper-containing subunits arranged in eight hexameric groups. In this study, we used the random conical tilt series method to do a three-dimensional (3D) reconstruction of Lp Hc observed in vitreous ice. This approach allowed the unambiguous determination of the handedness of the molecule. Lp Hc contains two superimposed 4 x 6mer structures possessing the same structural features as the other 4 x 6meric Hcs, namely flip and flop views and a rocking effect. Moreover, 3D fitting of the X-ray structure of subunit LpII with the reconstruction volume shows that the intra4 x 6meric contacts described in arthropod Hcs also occur within Limulus Hc. The two half-molecules composing the 8 x 6mer have their flop faces in contact (flop/flop association), the main links being formed by subunits LpIV. Model building shows that the flop/flop association is the only possible arrangement which allows the assembly of the whole particle. The two alternate constructions (flip/flop and flip/flip) are forbidden because of steric hindrance.

Algorithms↗

PubMed1996

Similar architectures of native and transformed human alpha2-macroglobulin suggest the transformation mechanism.

The refined three-dimensional structure of native human alpha2-macroglobulin (alpha2M) has been determined by cryoelectron microscopy and three-dimensional reconstruction. New features corresponding to "sigmoid arches," "basal bodies," and "apical connections" were observed in the molecule. Since similar elements are found in the architecture of transformed alpha2M, the 2 volumes were aligned in three dimensions. In their common orientations, they show many similarities except near the openings of the central chamber. In the native conformation, these apertures are fully opened, allowing the proteases to access the central chamber of the molecule, while in the transformed structure, they are partially closed. These structures suggest that alpha2M conformational change involves a strong lateral compression and a vertical stretching of the native particle seen in its four-petaled flower view to produce the H view of the transformed form. A model of structural transformation, in which all the parts of the alpha2M molecule seem involved in the entrapment of the proteinases is proposed.

Cryopreservation↗

PubMed1996

Three-dimensional reconstruction of the chlorocruorin of the polychaete annelid Eudistylia vancouverii.

The chlorocruorin of the polychaete Eudistylia vancouverii observed in the electron microscope in vitreous ice, was subjected to a three-dimensional (3D) reconstruction by the random conical tilt series method. The 3D volume with a resolution of 35 A reconstructed from 1062 images in top, side and intermediate view orientations has a D6 point-group symmetry. It possesses the characteristic hexagonal bilayer (HBL) appearance. Each hexagonal half-molecule comprises size hollow globular substructures (HGS) presumed to correspond to the dodecameric subunits. In projection, when the molecule is viewed along its 6-fold axis, the two halves are not perfectly eclipsed. The vertices of the upper hexagonal layer are 14 degrees rotated clockwise compared with those of the lower half. At a threshold displaying 100% of the expected molecular volume, the 3D volume contains in its center a flat hexagonal central mass disconnected from the rest of the volume. Several types of connections, termed c1 through c4, are visible between the HGSs. The c1 and c2 connections link the HGSs of the same hexagonal half-molecule. The c3 connections make a hexagonal inner bracelet linking the HGSs of each half-molecule. The c4 connections link pairs of HGSs superposed in the two hexagonal layers. Because of the half-molecules rotation around the 6-fold axis, the two HGSs linked by a c4 connection are not exactly superposed. It is proposed that the c3 and c4-connection bodies and less probably the flat central hexagonal mass are composed of chloroheme-deficient linker chains. When eroding the 3D volume by raising the threshold, the HGS appears composed of three elongated structures likely containing four globin chains. In addition, they show an approximate 3-fold symmetry. At high thresholds, two of these masses, dumbbell-shaped, separate into globular masses while the third structure remains compact as long as 1% of the molecular volume is displayed.

Animals↗

PubMed1995

Three-dimensional reconstruction of the hemocyanin of the protobranch bivalve mollusc Nucula hanleyi from frozen-hydrated specimens.

The didecameric hemocyanin of the bivalve mollusc Nucula hanleyi, observed in the electron microscope in vitreous ice, was subjected to a three-dimensional (3D) reconstruction by the random conical tilt series method. The 3D volume was analyzed by computing solid-body surface representations and slices through the volume and by eroding the structure progressively. The molecule was reconstructed from 288 and 63 images in the side- and end-on view orientations, respectively. It comprises three parts: one cylindrical wall composed of 10 oblique wall units and two collar complexes located at both ends of the cylinder and made up each of five arches and one annular collar. Erosion of the volume reveals that the wall looks like a segment of a five-stranded right-handed helix and that each oblique wall unit resembles a figure 8 inclined to the right. The 3D volumes reconstructed from Helix pomatia and N. hanleyi hemocyanins look perfectly similar, except that when the threshold is expressed as a function of the molecular volume left apparent, the various connections between the wall, the arches, and the collar disappear at a lower threshold in N. hanleyi than in H. pomatia. Conversely, with thresholds expressed as a fraction of the dynamic range of the 3D volume, the two structures are quite similar. This behavior means either that the molecular weights of Helix and Nucula hemocyanins (and therefore their molecular volumes) are not so different as indicated in the literature or that all the portions of Nucula hemocyanin have molecular weights lower than those of Helix hemocyanins.

Animals↗

PubMed1995

Three-dimensional reconstruction of the alpha D and beta C-hemocyanins of Helix pomatia from frozen-hydrated specimens.

The three-dimensional (3D) reconstructions of the di-decameric forms of alpha D and beta C-hemocyanins of the Roman snail Helix pomatia and of the decameric half molecules of alpha D-hemocyanin were carried out on frozen-hydrated specimens observed in the electron microscope by using the random conical tilt series method. The three 3D volumes were examined by computing solid-body surface representations and slices through the volume and by eroding the structure progressively through raising of the threshold. The di-decameric molecule of alpha D and beta C-hemocyanins, reconstructed from side views, are very similar and are composed of a cylindrical wall, comprising ten oblique wall units, and of two collar complexes located at both ends of the cylinder, comprising each five arches and an annular collar made up of five collar units. Erosion of the structure reveals that the wall looks like a segment of a five-stranded right-handed helix and that each oblique wall unit resembles a figure 8 inclined to the right. The decameric half molecule of alpha D-hemocyanin, reconstructed from end-on views, resembles the whole molecule, except that the collar is thinner and appears composed of five independent collar complex units. It is suggested that the difference in structural appearance of the collar complex between the whole and the half alpha D-hemocyanin may be due to the missing cone artifact, induced by the angular limitations imposed by the goniometer of the electron microscope. The comparison between the alpha D-hemocyanin and the beta C-di-decameric hemocyanin at high thresholds suggests that in the beta C-hemocyanin the oblique wall units of each half molecule may be linked by two connections, whereas in alpha D-hemocyanin there may be only one. This difference in the number of connections may be responsible for the lower stability of the alpha D molecule at high salt concentration.

Animals↗

PubMed1995

Three-dimensional reconstruction of Sepia officinalis hemocyanin from frozen-hydrated specimens.

The three-dimensional reconstruction of Sepia hemocyanin from randomly oriented native molecules was carried out by the method of the random conical tilt series on a frozen-hydrated specimen. As other molluscan hemocyanins, the molecule resembles a hollow cylinder or pentahedron composed of five dimeric subunits. Each dimeric subunit, composed of 16 functional units, comprises one wall oblique unit made up of 12 functional units and one arch made up of four functional units. The five wall oblique units are separated from each other by five oblique clefts bridged by the five arches, formerly termed collar structures. Each arch is composed of two types of functional units that are probably Soe, a functional unit absent in Octopus hemocyanin, and Soh, the C-terminal functional unit of the polypeptide chain. The architecture of the arches and their intramolecular location in front of the edges of the pentahedron are strongly reminiscent of the arches of Octopus hemocyanin. The D5 point-group symmetry of the molecule suggests that the orientation of the polypeptide chains is antiparallel as in Octopus hemocyanin. Several models of architecture compatible with these results are designed.

Animals↗

PubMed1995

Estimation of variance distribution in three-dimensional reconstruction. II. Applications.

A previously developed theory of three-dimensional (3-D) variance estimation [J. Opt. Soc. Am. A 12, 2615-2627 (1995)] is applied to the structural study of a hemocyanin-Fab complex with the electron microscope. The precise locations of structurally variable regions of the macromolecule are determined from the 3-D variance maps. The structural differences among different classes of the macromolecular complex are assessed by the use of the statistical t-test, and the 3-D antibody binding sites are revealed. From a model analysis, a rule is demonstrated for visually identifying a 3-D conformational change by the inspection of the 3-D variance map. Our analysis lays the foundation for numerous practical applications of variance estimation in the 3-D imaging of macromolecules.

Analysis of Variance↗