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PubMed1984

Computer graphics modelling and the specificity of renins.

Mouse submaxillary, mouse kidney and human renins have been modelled using the three-dimensional structure of the homologous endothiapepsin, which has been defined by high-resolution X-ray analysis, and the amino acid sequences derived from protein, complementary DNA or gene sequencing. These computer graphics studies have shown that all renins can adopt three-dimensional structures similar to those of other aspartic proteinases with small insertions and deletions at the surface and often at beta-turns. The catalytically essential aspartates lie at the centre of a deep and extended cleft, and differences in the subsites, especially at S3' have been correlated with the known specificities of the renins. The models have shown that various residues on the surfaces of the renins adjacent to the active site cleft may play a part in recognizing and binding angiotensinogen. Reasons for a neutral pH optima have also been suggested.

Amino Acid Sequence↗
PubMed1993

The phylogeny of autotrophic ammonia-oxidizing bacteria as determined by analysis of 16S ribosomal RNA gene sequences.

Partial sequences of the 16S ribosomal RNA genes of eleven autotrophic ammonia-oxidizing bacteria were determined by PCR amplification from small amounts of heat-lysed biomass followed by direct sequencing of PCR products. The sequences were aligned with those of representative Proteobacteria and phylogenetic trees inferred using both parsimony and distance matrix methods. This confirmed that the autotrophic ammonia-oxidizers comprise two major lines of descent within the Proteobacteria. Nitrosomonas spp., Nitrosococcus mobilis, and strains of Nitrosovibrio, Nitrosospira and Nitrosolobus were located in the beta-subdivision. The recovery of Nitrosococcus oceanus strains as a deep branch in the gamma-subdivision supported the RNA catalogue data which had indicated that the genus Nitrosococcus is polyphyletic. The autotrophic ammonia-oxidizing bacteria of the beta-Proteobacteria formed a coherent group which is interpreted as representing a single family. Within this clade, the genera Nitrosovibrio, Nitrosospira and Nitrosolobus exhibited very high levels of homology in their 16S ribosomal RNA gene sequences and can be accommodated within a single genus. Separation of these genera is currently based entirely on gross morphological differences and these can now be considered more appropriate for the identification of species within this group. It is therefore proposed that Nitrosolobus, Nitrosovibrio and Nitrosospira strains be reclassified in a single genus for which the name Nitrosospira has priority.

Ammonia↗
PubMedDate not supplied

MR and MR angiography of Sturge-Weber syndrome.

PURPOSE: To assess the potential of magnetic resonance angiography (MRA) as an adjunct to spin-echo sequences in evaluating the cerebral vascular anomalies seen in Sturge-Weber syndrome. METHODS: Four pediatric patients with Sturge-Weber syndrome were evaluated with conventional MR imaging and with arterial and venous MRA. Resultant images were evaluated for evidence of volume loss, cortical enhancement, vascular anomalies, and enlarged choroid plexus. RESULTS: Venous MRA revealed reduced flow of the transverse sinuses and jugular veins, prominent deep collateral venous system, and a lack of superficial cortical veins. Arterial MRA, performed in all cases, revealed a reduced flow signal from the left middle cerebral artery in one hemiparetic patient and angiomatous changes of high branches of a middle cerebral artery in two patients. CONCLUSION: Arterial and, in particular, venous MRA can be useful adjuncts to standard spin-echo sequences in diagnosing Sturge-Weber syndrome.

Brain↗
PubMed2006

intraoperative neuronavigation using diffusion tensor MR tractography for the resection of a deep tumor adjacent to the corticospinal tract.

OBJECTIVE AND IMPORTANCE: Delineation of cerebral white matter tracts using MR tractography adds essential information for planning intracranial surgery. Integrating tractography with intraoperative neuronavigation may reduce the likelihood of new neurological deficits after surgery done to remove tumors adjacent to the projection fibers of eloquent cortex. We report the utility of such integration for the resection of deep (paraventricular) tumors. CLINICAL PRESENTATION: A 67-year-old male with malignant melanoma underwent stereotactic radiosurgery for a single metastasis within the paraventricular white matter of the right frontal lobe near the corticospinal tract. The lesion doubled in size within 12 months of radiotherapy. Surgical extirpation was performed aided by intraoperative neuronavigation. TECHNIQUE: MR images of the brain including MR tractography and post-contrast T1-weighted sequences were acquired and imported into a neuronavigational workstation. Asymmetric fusion of contrast-enhanced images and tractography was employed to assist in preservation of the integrity of critical white matter tracts during the surgical procedure. CONCLUSION: Inclusion of tractography in standard imaging protocols for neuronavigational systems may increase the safety of neurosurgical intervention near white matter tracts, including deep areas adjacent to the ventricles.

Aged↗
PubMed2001

Accuracy for detection of simulated lesions: comparison of fluid-attenuated inversion-recovery, proton density--weighted, and T2-weighted synthetic brain MR imaging.

OBJECTIVE: The objective of our study was to determine the effects of MR sequence (fluid-attenuated inversion-recovery [FLAIR], proton density--weighted, and T2-weighted) and of lesion location on sensitivity and specificity of lesion detection. MATERIALS AND METHODS: We generated FLAIR, proton density-weighted, and T2-weighted brain images with 3-mm lesions using published parameters for acute multiple sclerosis plaques. Each image contained from zero to five lesions that were distributed among cortical-subcortical, periventricular, and deep white matter regions; on either side; and anterior or posterior in position. We presented images of 540 lesions, distributed among 2592 image regions, to six neuroradiologists. We constructed a contingency table for image regions with lesions and another for image regions without lesions (normal). Each table included the following: the reviewer's number (1--6); the MR sequence; the side, position, and region of the lesion; and the reviewer's response (lesion present or absent [normal]). We performed chi-square and log-linear analyses. RESULTS: The FLAIR sequence yielded the highest true-positive rates (p < 0.001) and the highest true-negative rates (p < 0.001). Regions also differed in reviewers' true-positive rates (p < 0.001) and true-negative rates (p = 0.002). The true-positive rate model generated by log-linear analysis contained an additional sequence-location interaction. The true-negative rate model generated by log-linear analysis confirmed these associations, but no higher order interactions were added. CONCLUSION: We developed software with which we can generate brain images of a wide range of pulse sequences and that allows us to specify the location, size, shape, and intrinsic characteristics of simulated lesions. We found that the use of FLAIR sequences increases detection accuracy for cortical-subcortical and periventricular lesions over that associated with proton density- and T2-weighted sequences.

Adult↗
PubMed2000

Temperature monitoring in fat with MRI.

The aim of the study was to test the hypothesis that fast spin echo T(1)-weighted images can be used to quantify the temperature in fat during thermal therapy in vivo. An MR compatible positioning device was used to manipulate focused ultrasound transducers in an MRI scanner. This system was used to sonicate fat tissue around the kidneys of 12 rabbits at various power levels for 10 to 20 sec. The scan parameters of T(1)-weighted fast spin echo (FSE) sequence were varied to optimize signal intensity characteristics while maintaining short scan times. An invasive optical probe was used to calibrate the temperature related signal intensity changes. For the T(1)-weighted FSE sequence, the signal intensity decreased with the temperature elevation at the rate of 0.97+/-0.02%/ degrees C. The single focused transducer produced a contrast-to-noise ratio more than 10 at power levels below the tissue damage threshold. The signal intensity was linearly dependent on the power, despite the measured temperatures being well above the coagulation threshold. This study demonstrates that T(1)-weighted FSE MRI sequences can be used to quantify the temperature elevation in fat in vivo during short focused ultrasound exposures. This can be very important for breast tumor surgery, fat ablation, and for treating deep seated tumors through superficial fat layers. Magn Reson Med 43:901-904, 2000.

Adipose Tissue↗
PubMed1992

Subunit assembly and active site location in the structure of glutamate dehydrogenase.

The three-dimensional crystal structure of the NAD(+)-linked glutamate dehydrogenase from Clostridium symbiosum has been solved to 1.96 A resolution by a combination of isomorphous replacement and molecular averaging and refined to a conventional crystallographic R factor of 0.227. Each subunit in this multimeric enzyme is organised into two domains separated by a deep cleft. One domain directs the self-assembly of the molecule into a hexameric oligomer with 32 symmetry. The other domain is structurally similar to the classical dinucleotide binding fold but with the direction of one of the strands reversed. Difference Fourier analysis on the binary complex of the enzyme with NAD+ shows that the dinucleotide is bound in an extended conformation with the nicotinamide moiety deep in the cleft between the two domains. Hydrogen bonds between the carboxyamide group of the nicotinamide ring and the side chains of T209 and N240, residues conserved in all hexameric GDH sequences, provide a positive selection for the syn conformer of this ring. This results in a molecular arrangement in which the A face of the nicotinamide ring is buried against the enzyme surface and the B face is exposed, adjacent to a striking cluster of conserved residues including K89, K113, and K125. Modeling studies, correlated with chemical modification data, have implicated this region as the glutamate/2-oxoglutarate binding site and provide an explanation at the molecular level for the B type stereospecificity of the hydride transfer of GDH during the catalytic cycle.

Amino Acid Sequence↗
PubMed2001

Phylogeny and Abundance of Novel Denitrifying Bacteria Isolated from the Water Column of the Central Baltic Sea.

The Baltic Sea is an estuarine ecosystem where denitrification in the low oxic and anoxic parts of the deep water contributes significantly to the nitrogen budget. Seventy-six heterotrophic, denitrifying, strains have been isolated by four cultivation procedures from the water column of the Gotland Deep, the main anoxic basin of the Central Baltic. Phylogenetic positions of representative strains of 10 different genotypes, grouped beforehand by low molecular weight (LMW) RNA profiling, were estimated by 16S rRNA sequence analysis. The 10 genotypes consisted of two members of the alpha subclass of the Proteobacteria and eight members of the gamma subclass. The major fraction of the genotypes was considered to be novel species or even genera. The gamma-Proteobacteria were the most abundant of the denitrifying isolates (96% of the total isolates) with a predominance of Shewanella baltica (77%), whereas the alpha-Proteobacteria were represented by single isolates. The diversity spectrum of Baltic sea denitrifying isolates was rather distinct from that previously described for marine and freshwater environments. Denitrifying bacteria could be isolated from all depths of the water column with the highest diversity and abundance of genotypes detected in samples of the oxic-anoxic interface, the layer of high in situ denitrification. For success of isolation of phylogenetically divers denitrifiers, both sample origin and cultivation procedure were observed to have an impact.

Journal Article↗
PubMed2004

Anaerofustis stercorihominis gen. nov., sp. nov., from human feces.

Phenotypic and phylogenetic studies were performed on an unidentified Gram-positive, strictly anaerobic, non-spore-forming, rod-shaped bacterium isolated from human feces. The organism was catalase-negative, resistant to 20% bile, produced acetic and butyric acids as end products of glucose metabolism, and possessed a G+C content of approximately 70 mol%. Comparative 16S rRNA gene sequencing demonstrated that the unidentified bacterium was a member of the Clostridium sub-phylum of the Gram-positive bacteria, and formed a loose association with rRNA cluster XV. Sequence divergence values of 12% or greater were observed between the unidentified bacterium and all other recognized species within this and related rRNA clusters. Treeing analysis showed the unknown anaerobe formed a deep line branching near to the base of rRNA cluster XV and phylogenetically represents a hitherto unknown taxon, distinct from Acetobacterium, Eubacterium sensu stricto, Pseudoramibacter and other related organisms. Based on both phylogenetic and phenotypic evidence, it is proposed that the unknown bacterium from feces be classified in a new genus Anaerofustis, as Anaerofustis stercorihominis sp. nov. The type strain of Anaerofustis stercorihominis is ATCC BAA-858(T)=CCUG 47767(T).

Journal Article↗
PubMed2000

Crystal structure of protein isoaspartyl methyltransferase: a catalyst for protein repair.

BACKGROUND: Formation of isoaspartyl residues is one of several processes that damage proteins as they age. Protein L-isoaspartate (D-aspartate) O-methyltransferase (PIMT) is a conserved and nearly ubiquitous enzyme that catalyzes the repair of proteins damaged by isoaspartyl formation. RESULTS: We have determined the first structure of a PIMT from crystals of the T. maritima enzyme complexed to S-adenosyl-L-homocysteine (AdoHcy) and refined it to 1.8 A resolution. Although PIMT forms one structural unit, the protein can be divided functionally into three subdomains. The central subdomain closely resembles other S-adenosyl-L-methionine-dependent methyltransferases but bears a striking alteration of topological connectivity, which is not shared by any other member of this family. Rather than arranged as a mixed beta sheet with topology 6 upward arrow7 downward arrow5 upward arrow4 upward arrow1 upward arrow2 upward arrow3 upward arrow, the central sheet of PIMT is reorganized to 7 upward arrow6 downward arrow5 upward arrow4 upward arrow1 upward arrow2 upward arrow3 upward arrow. AdoHcy is largely buried between the N-terminal and central subdomains by a conserved and largely hydrophobic loop on one rim of the binding cleft, and a conserved Ser/Thr-rich beta strand on the other. The Ser/Thr-rich strand may provide hydrogen bonds for specific interactions with isoaspartyl substrates. The side chain of Ile-206, a conserved residue, crosses the cleft, restricting access to the donor methyl group to a deep well, the putative isoaspartyl methyl acceptor site. CONCLUSIONS: The structure of PIMT reveals a unique modification of the methyltransferase fold along with a site for specific recognition of isoaspartyl substrates. The sequence conservation among PIMTs suggests that the current structure should prove a reliable model for understanding the repair of isoaspartyl damage in all organisms.

Amino Acid Sequence↗
PubMed2002

High resolution contrast enhanced MR-angiography of the hand arteries: preliminary experiences.

BACKGROUND: In contrast to magnetic-resonance-angiography (MRA) of the peripheral vessels of the lower extremity, which gains more and more clinical application, MRA of the hand arteries is still exceptional. Our objective was to introduce an appropriate protocol for high resolution contrast-enhanced MR-angiography of the hand arteries. PATIENTS AND METHODS: 7 healthy volunteers and 13 patients with suspected hand artery obstructions underwent MRA. The examinations were performed on a 1.5 T system equipped with a flexible surface coil. A modified 3D-gradient-echo sequence was used. Criteria for image analysis were the overall image quality, vessel visibility and the timing of the contrast material bolus. RESULTS: In the volunteer group delineation of the superficial or deep palmar arch, common palmar digital arteries and of the proximal and middle segments of the digital arteries was possible. No pathologic findings were seen in the volunteer group. In 10 patients MRA revealed pathologic findings. In 9 examinations bolus-timing was correct, 7 examinations showed incomplete arterial enhancement, 4 examinations showed venous overlay. CONCLUSIONS: Contrast enhanced MR-angiography of the hand arteries in the described technique is a promising method. Compared to intraarterial digital subtraction angiography (IA-DSA) MRA still has limitations concerning spatial and temporal resolution. For clinical evaluation comparative studies with IA-DSA are necessary.

Adult↗
PubMed2006

Equine herpesvirus 2-associated granulomatous dermatitis in a horse.

Granulomatous dermatitis in horses has been linked to many etiologies, including various parasites, fungi, and bacteria. Idiopathic forms of granulomatous inflammation-producing diseases, some of which are localized to the skin, also have been reported in horses. Herein we describe a case of recurrent equine granulomatous skin disease characterized by intranuclear viral inclusions within macrophages and giant cells. The histologic changes were primarily noted in the deep dermis and included multifocal to coalescing areas of necrosis marked by histiocytic cell infiltration and presence of giant cells. Electron microscopic examination revealed intranuclear and intracytoplasmic viral particles consistent with herpesvirus. Sequence results of the polymerase chain reaction product were consistent with equine herpesvirus 2, adding another possible etiology to the list of differentials in cases of equine granulomatous skin disease.

Animals↗
PubMed2003

Genetic differences within and between species of deep-sea crabs (chaceon) from the North Atlantic Ocean.

The deep-sea red crab Chaceon quinquedens is a commercially important crustacean on the Atlantic continental shelf and slope of North America. To assess genetic subdivision in C. quinquedens, we examined the nucleotide sequence of the mitochondrial 16S rDNA gene and the internal transcribed spacers (ITS) of the nuclear ribosomal repeat in samples from southern New England and the Gulf of Mexico. We compared those data to sequences from two congeners, a sympatric species from the Florida coast, C. fenneri, and an allopatric eastern Atlantic species, C. affinis. The 16S rDNA data consisted of 379 aligned nucleotides obtained from 37 individuals. The greatest genetic difference among geographical groups or nominal species was between C. quinquedens from southern New England and C. quinquedens from the Gulf of Mexico. Haplotypes from these two groups had a minimum of 10 differences. All 11 C. fenneri samples matched the most common haplotype found in C. quinquedens from the Gulf of Mexico, and this haplotype was not detected in C. quinquedens from southern New England. The three haplotypes of C. affinis were unique to that recognized species, but those haplotypes differed only slightly from those of C. fenneri and C. quinquedens from the Gulf of Mexico. Based on 16S rDNA and ITS data, genetic differences between C. quinquedens from southern New England and the Gulf of Mexico are large enough to conclude that these are different fishery stocks. Our results also indicate that the designation of morphological species within the commercially important genus Chaceon is not congruent with evolutionary history. The genetic similarity of C. affinis from the eastern Atlantic and C. quinquedens from the Gulf of Mexico suggests these trans-Atlantic taxa share a more recent common history than the two populations of "C. quinquedens" that we examined.

Animals↗
PubMedDate not supplied

Engineering crops, a deserving venture.

Plant transformation has had a deep impact on several aspects of basic and applied research. Genetic transformation has offered new opportunities compared to traditional breeding practises since it allows the integration into a host genome of specific sequences leading to a strong reduction of the casualness of gene transfer. One of the first target areas was plant protection against pests, pathogens and environmental stresses while the recent plant engineering programs are aimed at increasing food quality, in particular at increasing nutritional characteristics of food crops. Moreover, transgenic plants, tissue or cell cultures represent an attractive biological system for producing heterologous proteins since they offer economic and qualitative benefits. High yield production can be obtained and large-scale commercial production will take advantage of the existing infrastructure for crop cultivation, processing and storage. There are also qualitative benefits since protein synthesis secretion and post-translational modifications are similar in plants and animal cells. There are no human viral pathogens harboured by plants: thus, especially for pharmaceuticals, plants represent the safer production system. Plant transformation has become an essential instrument also for basic research, in particular for the functional characterisation of genes identified by sequencing of whole genomes. Large collections of insertion mutants have been obtained in the model plant Arabidopsis to provide a high level of genome saturation that means 95% chance of inactivating any gene at least once. To instil greater public confidence in modern plant biotechnology recent advances have already been made to overcome the potential risks for human health and environment.

Agriculture↗
PubMed2002

Identification of novel membrane proteins by searching for patterns in hydropathy profiles.

A technique has been developed to search a proteome database for new members of a functional class of membrane protein. It takes advantage of the highly conserved secondary structure of functionally related membrane proteins. Such proteins typically have the same number of transmembrane domains located at similar relative positions in their polypeptide sequence. This gives rise to a characteristic pattern of peaks in their hydropathy profiles. To conduct a search, each member of a polypeptide database is converted to a hydropathy profile, peaks are automatically detected, and the pattern of peaks is compared with a template. A template was designed for the acetylcholine (ACh) and glycine receptors of the cys-loop receptor superfamily. The key feature was a closely spaced triplet of hydropathy peaks bracketed by deep valleys. When applied to the human proteome the search procedure retrieved 153 profiles with a receptor-like triplet of peaks. The approach was highly selective with 70% of the retrieved profiles annotated as known or putative receptors. These included ACh, glycine, gamma-amino butyric acid and serotonin receptors, which are all related by sequence. However, ionotropic glutamate receptors, which have almost no sequence homology with ACh receptors, were also retrieved. Thus, the strategy can find members of a functional class that cannot be identified by sequence alignment. To demonstrate that the strategy can easily be extended to other membrane protein families, a template was developed for the neurotransmitter/Na+ symporter family, and similar results were obtained. This approach should prove a useful adjunct to sequence-based retrieval tools when searching for novel membrane proteins.

Databases, Protein↗
PubMed1997

Expression of functionally active cytochrome b5 in Escherichia coli: isolation, purification, and use of the immobilized recombinant heme protein for affinity chromatography of electron-transfer proteins.

Cytochrome b5 is an integral membrane protein which is localized in endoplasmic reticulum membranes. In this paper we present the results on expression in E. coli, purification, and characterization of recombinant rat cytochrome b5. The full-length cDNA for rat liver microsomal cytochrome b5 has been modified using polymerase chain reaction (PCR) to introduce corresponding restriction sites as well as to insert silent mutations in the N-terminal sequence to increase the content of A and T nucleotides that prevents formation of elements of secondary structure of the mRNA transcripts and facilitates high expression. The expression plasmid was constructed by cloning of amplified cDNA to pCWori+ plasmid and used for transformation of E. coli DH5 alpha. The optimization of recombinant cytochrome b5 expression procedure induces expression level up to 3000 nmoles per liter of growth medium; this confers in the cells a deep pink color. The most interesting fact is that cytochrome b5 is expressed in this system in the reduced state. Recombinant cytochrome b5 was purified from solubilized cell membranes by a combination of ion-exchange chromatography and gel filtration. During purification, part of the cytochrome b5 is subjected to limited proteolysis with formation of truncated form. Sequencing of the N-terminal part of the recombinant cytochrome b5 indicates that it coincides with the sequence of rat cytochrome b5. Recombinant cytochrome b5 was found to have physicochemical, catalytic, and immunochemical properties to that of the native protein and was used as an efficient affinity matrix for purification of the various electron-transfer proteins.

Aminolevulinic Acid↗
PubMed1992

Emerging principles for the recognition of peptide antigens by MHC class I molecules.

Class I major histocompatibility complex (MHC) molecules interact with self and foreign peptides of diverse amino acid sequences yet exhibit distinct allele-specific selectivity for peptide binding. The structures of the peptide-binding specificity pockets (subsites) in the groove of murine H-2Kb as well as human histocompatibility antigen class I molecules have been analyzed. Deep but highly conserved pockets at each end of the groove bind the amino and carboxyl termini of peptide through extensive hydrogen bonding and, hence, dictate the orientation of peptide binding. A deep polymorphic pocket in the middle of the groove provides the chemical and structural complementarity for one of the peptide's anchor residues, thereby playing a major role in allele-specific peptide binding. Although one or two shallow pockets in the groove may also interact with specific peptide side chains, their role in the selection of peptide is minor. Thus, usage of a limited number of both deep and shallow pockets in multiple combinations appears to allow the binding of a broad range of peptides. This binding occurs with high affinity, primarily because of extensive interactions with the peptide backbone and the conserved hydrogen bonding network at both termini of the peptide. Interactions between the anchor residue (or residues) and the corresponding allele-specific pocket provide sufficient extra binding affinity not only to enhance specificity but also to endure the presentation of the peptide at the cell surface for recognition by T cells.

Amino Acid Sequence↗
PubMed2005

Worldwide genomic diversity of the human papillomaviruses-53, 56, and 66, a group of high-risk HPVs unrelated to HPV-16 and HPV-18.

Among more than 200 human papillomavirus (HPV) types presumed to exist, 18 "high-risk" HPV types are frequently found in anogenital cancer. The best studied types are HPV-16 and 18, which are only distantly related to one another and form two separate phylogenetic branches, each including six closely related types. HPV-30, 53, 56, and 66 form a third phylogenetic branch unrelated to HPV-16 and 18. Worldwide comparison of HPV-16 and 18 isolates revealed a distribution of variant genomes that correlated with the geographic origin and the ethnicity of the infected cohort and led to the concept of unique African, European, Asian, and Native American HPV-16 and 18 variants. Here, we address the question whether similar phylogenies are found for HPV-53, 56, and 66 by determining the sequence of the long control regions (LCR) of these HPVs in samples from Europe, Asia, and Africa, and from immigrant societies in North and South America. Phylogenetic trees calculated from point mutations and a few insertions/deletions affecting 2-4.2% of the nucleotide sequences were distinct for each of the three HPVs and divergent from HPV-16 and 18. In contrast to the "star-phylogenies" formed by HPV-16 and 18 variants, 44 HPV-53 isolates represented nine variants, which formed two deep dichotomic branches reminiscent of the beginning split into two new taxa, as recently observed for subtypes of HPV-44 and 68. A total of 66 HPV-56 isolates represented 17 variants, which formed three branches preferentially containing European, Asian, and African variants. Variants of a fourth branch, deeply separated from the other three, were characterized by a 25 bp insertion and created a dichotomy rather than star-like phylogeny. As it contained isolates from cohorts in all continents, it may have evolved before the spread of humans into all continents. 18 of 31 HPV-66 isolates represented the prototype clone, which was found in all parts of the world, while the remaining 13 clones formed 11 branches without any geographic association. Our findings confirm the notion of a quantitatively limited genomic diversity of each HPV type with some correlation to the geographic origin of the sample. In addition, we observed in some variants of these three HPV types mutations that affect the amino acid sequence of the E6 oncoproteins and the L1 capsid protein, supporting the possibility of immunogenic and oncogenic diversity between variants of any HPV type.

Aleutian Mink Disease Virus↗