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Vol. 96, Issue 10, 5581-5585, May 11, 1999
* Max Planck Institute for Evolutionary Anthropology, Inselstrasse
22, D-04103 Leipzig, Germany; Edited by L. L. Cavalli-Sforza, Stanford University School of
Medicine, Stanford, CA, and approved February 17, 1999 (received for review December 28, 1998)
The DNA sequence of the second hypervariable region of the
mitochondrial control region of the Neandertal type specimen, found in
1856 in central Europe, has been determined from 92 clones derived from
eight overlapping amplifications performed from four independent
extracts. When the reconstructed sequence is analyzed together with the
previously determined DNA sequence from the first hypervariable region,
the Neandertal mtDNA is found to fall outside a phylogenetic tree
relating the mtDNAs of contemporary humans. The date of divergence
between the mtDNAs of the Neandertal and contemporary humans is
estimated to 465,000 years before the present, with confidence limits
of 317,000 and 741,000 years. Taken together, the results support the
concept that the Neandertal mtDNA evolved separately from that of
modern humans for a substantial amount of time and lends no support to
the idea that they contributed mtDNA to contemporary modern humans.
The role of Neandertals with respect to the evolution of
anatomically modern humans is controversial. Although some
paleontologists view Neandertals as a distinct branch in hominid
evolution that became extinct without any direct genetic contribution
to present-day humans (1), others consider the Neandertals to be among
the direct ancestors of modern Europeans (2). Recently, as a part of an
interdisciplinary project of the Rheinisches Landesmuseum Bonn (3, 4),
the DNA sequence of the first hypervariable region (HVRI) of the mtDNA
from the Neandertal type specimen was determined (5). When compared
with HVRI sequences of contemporary humans, the Neandertal mtDNA tended
to fall outside the variation of modern humans. Furthermore,
phylogenetic analyses suggested that the Neandertal mtDNA was an
outgroup to the mtDNAs of modern humans, and the age of the most recent
common ancestor (MRCA) of the mtDNAs of the Neandertal and modern
humans was estimated to be about four times older than the age of the
MRCA of modern human mtDNAs. These results indicate that the Neandertal
mtDNA gene pool evolved for a substantial time period as an entity
distinct from modern humans and give no indication that Neandertals
contributed mtDNA to modern humans (5, 6).
However, because these analyses were based on a DNA sequence of only
333 bp, the results are less than conclusive. For example, the support
for the placement of the Neandertal mtDNA outside the variation of
modern human mtDNA in the phylogenetic tree was merely 89% (5). To
better estimate the relationship of the Neandertal mtDNA to the current
mtDNA gene pool, we have determined 340 bp of the second mtDNA HVR
(HVRII) from the Neandertal type specimen and analyzed the relationship
of the combined sequences to the contemporary human mtDNA gene pool.
Experimental Procedures.
Sampling, precautions against
contamination, DNA extraction, PCR amplifications, cloning of PCR
products, and sequencing of clones were performed as described (5).
Extracts A, B, and C were prepared previously (5), whereas extracts D
and E were prepared for this work from 0.4 g of bone each.
Extracts A, B, and C were known to yield PCR products that contained
various proportions of modern human mtDNA sequences in addition to the Neandertal sequence (5). To test the degree of contamination of
extracts D and E, PCRs were performed for a part of HVRI, which had
been determined previously (primers L16209 and H16271; ref. 5). The PCR
products were cloned, and 10 clones each were sequenced. In both
extracts, 8 of 10 clones carried 7 substitutions and an adenosine
insertion was determined for the Neandertal in this region (5), whereas
two clones were identical to the reference sequence (data not shown).
Thus, as in the case of extracts A and B, a small proportion of
contaminating sequences is present in extracts D and E. Extract C,
which was prepared in another laboratory, contains a majority of
contaminating modern human DNA (5). Thus, whenever this extract was
used, primers specific for putative Neandertal sequences determined
from adjacent segments were used (cf. Fig. 1). There were 6, 2, and 19 clones derived from amplifications C21, C23, and E24 (Fig. 1),
respectively, that contained sequences with only one or no difference
from the reference sequence (7). These clones (not shown) were
considered contaminants and were not included in the reconstruction of
the Neandertal sequence. For the other amplifications, all clones sequenced and the primers used are shown in Fig. 1.
Alignments and Sequence Analyses.
For the analysis of the HVRI
and HVRII sequences, the Neandertal sequences were aligned to a data
set of 663 contemporary mtDNA lineages, i.e., distinct mtDNA sequences
found among 682 contemporary humans (8). All human sequences with
ambiguities in the reported sequences were excluded before the
analysis. In addition, nine mtDNA lineages from seven common
chimpanzees and two bonobos ("pygmy chimpanzees") were used
(9-14). At positions where insertions/deletions occurred between the
sequences of the apes, humans and the Neandertal were excluded from the
alignment. Sequence comparisons thus were based on a total of 600 nucleotide positions, encompassing positions 16024-16365 and 73-340,
but excluding positions 16078, 16166, 252, 291, 299, and 317-321
(numbering according to ref. 7). Pairwise sequence differences were
calculated by using unpublished software by A. von Haeseler (Max Planck
Institute for Evolutionary Anthropology Leipzig, Germany).
Evolution
DNA sequence of the mitochondrial hypervariable region II from
the Neandertal type specimen
,
, and Landschaftsverband Rheinland,
Rheinisches Amt für Bodendenkmalpflege/Rheinisches
Landesmuseum, Bonn, Endenicher Strasse 133, D-53115 Bonn, Germany; and
Höhere Berufsfachschule für
präparationstechnische Assistenten, Markstrasse 185, D-44799
Bochum, Germany
ABSTRACT
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS AND DISCUSSION
CONCLUSIONS
REFERENCES
INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS AND DISCUSSION
CONCLUSIONS
REFERENCES
MATERIALS AND METHODS
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS AND DISCUSSION
CONCLUSIONS
REFERENCES
Nei algorithm (19) as implemented in PUZZLE 4.0. The parameters 
(transition/transversion
ratio), 
(purine/pyrimidine transition ratio), and 
, which
describes the distribution of the evolutionary rates of individual
nucleotide positions (20, 21), were estimated from the human sequences
by using PUZZLE 4.0. Means and SDs of the
genetic distances within and between species were calculated by using
the program EXCEL 4.0.
chimpanzee split, and the lower confidence limit of the genetic
distance and the older date for the humanchimpanzee split. These two
rates, in turn, were used to calculate the lower and upper limits of
the age of the MRCA of the human and chimpanzee mtDNA gene pools.
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RESULTS AND DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS AND DISCUSSION
CONCLUSIONS
REFERENCES
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Retrieval of the Neandertal HVRII. Primers designed to amplify human and chimpanzee mtDNA sequences were used to amplify a 122-bp segment (including primers) of HVRII from extract B, prepared from the 0.4 g of the right humerus of the Neandertal type specimen (24). A weak amplification product could be visualized on an agarose gel. This product was reamplified and cloned in a plasmid vector, and the inserts of 13 clones were sequenced (Fig. 1, B18). All clones carried four identical substitutions from the contemporary human reference sequence (7). Furthermore, two other positions differed from the reference sequence in six and seven clones, respectively, and four more positions showed substitutions in single clones. The same primers were used to amplify the same DNA segment from a different extract (Fig. 1, D20). Among the seven clones sequenced, the four substitutions found in all clones of the first amplification were found in all of these clones, with the sole exception of a G at position 189 in one of the clones. Neither the four singleton substitutions nor the two substitutions observed in several clones from the first amplification were seen among the clones from the second amplification. However, three more singleton substitutions were observed at positions that showed no variation among the first amplification. Substitutions that are not reproducible between amplifications are likely to be due to nucleotide misincorporations during the PCR, which may be induced by damage present in ancient DNA (25). That two nonreproducible substitutions occur in a large proportion of clones from one of the amplifications indicates that the amplifications start from very few template molecules, a supposition that agrees with the quantitation performed previously (5). When the sequence with the four substitutions seen in both amplifications was compared with a collection of 951 contemporary human mtDNA control region lineages (8), this combination of substitutions was not found, although all four positions are variable among humans.
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Authenticity.
The sequence determined was considered to be
derived from the mtDNA of the Neandertal individual for the following
reasons. (i) An analysis of the state of preservation of
amino acids in the bone (5) has shown that the conditions under which
the bone has been preserved are compatible with macromolecular
preservation. (ii) The DNA sequence could be amplified
reproducibly from different extracts. Because the amount of bone
available for extractions is limited, the HVRII sequence was not
reproduced from an independent extract in another laboratory. However,
this was done for the HVRI sequence determined previously (5). For the
HVRII sequence, the extract prepared at Penn State University (extract
C) yielded the same sequence as extracts prepared in Munich.
(iii) The DNA sequence falls as an outgroup to modern human
sequences in phylogenetic analyses (see below), an observation that may
be taken to support that it is derived from the bone. However, in some
cases, divergent mtDNA sequences derived from amplifications of
contemporary DNA containing nuclear insertions of mtDNA segments have
been misidentified as ancient sequences (26). Therefore, we designed a
primer pair (NL152, cf. Fig. 1 and NH243 5'-TGG CTG TGC A A CAT TTA
GTC-3') that matches the sequence from the Neandertal type specimen and not contemporary human mtDNA sequences. Under amplification conditions that allow less than one copy of the Neandertal sequence per genome of
human genomic DNA to be amplified, these primers failed to produce
products in amplifications attempted from nine Africans, six Europeans,
eight Asians, and three Australians/Oceanians. This makes a nuclear
insertion an unlikely source of the sequence. (iv) If some
form of miscoding DNA damage that was highly sequence-specific were
prevalent in the Neandertal DNA molecules, this would result in
nucleotide substitutions that would be reproduced between independent amplifications and thus would be mistaken for substitutions in the
authentic Neandertal DNA sequence. We consider this unlikely because 37 of 38 positions in which a substitutional difference between the
Neandertal and reference sequence are observed in HVRI and HVRII also
show differences among modern humans, chimpanzees, and bonobos. Because
295 of 600 positions studied are variable in this data set, this would
be an extremely unlikely result (P < 1.13 × 10
11) if the substitutions in the Neandertal
were generated by a process different from the process generating the
differences in the contemporary species, for example, some form of
postmortem chemical damage.
Sequence Comparisons. Among the 340 positions determined for HVRII, 11 transitional differences from the reference sequence (7) were identified. In addition, an insertion of three thymine residues occurs in a C-rich region after position 307 that shows length variation in humans (8).
To estimate the relationship of the Neandertal mtDNA to that of contemporary humans, positions 73-340 of HVRII were joined with positions 16024-16365 of HVRI and aligned to the homologous sequences from 151 Africans, 472 Europeans, 41 Asians, 10 Native Americans, and 15 Australian/Oceanians as well as 7 chimpanzees and 2 bonobos. Positions at which insertions/deletions occurred were excluded. Some humans shared the same sequences such that the data set could be collapsed to 663 different mitochondrial lineages. The contemporary human mtDNA lineages differ at an average of 10.9 positions from one another and at 35.3 positions from the Neandertal (Table 1). Thus, on average, the Neandertal mtDNA has more than three times as many differences from modern human sequences as the latter have between them. In addition to the substitutions, the Neandertal sequences carry an insertion of an A after position 16263 in HVRI as well as the insertion of three T residues in HVRII. It may be noted that a small fraction (0.037%) of the interhuman comparisons are larger than the smallest distance (29 substitutions) between the Neandertal and humans.
|
Phylogenetic Analysis. The observed nucleotide differences among all pairs of sequences of the Neandertal, the 663 modern humans, and the 7 chimpanzees and 2 bonobos were corrected for multiple substitutions, and a phylogenetic tree was constructed by using the neighbor-joining algorithm (17). In this tree the Neandertal forms the outgroup to the modern human mtDNAs (Fig. 2). The reliability of the branch connecting the Neandertal mtDNA with that of the modern humans was tested by the likelihood-mapping approach (18), where quartets of sequences involving the Neandertal, a chimpanzee or bonobo, and two humans were analyzed such that the probability of sampling each human sequence at least once was 0.96. For each quartet, the likelihood of each of the three possible tree topologies was calculated. In 100% of the 1,898,505 quartets tested the most likely topology had the Neandertal mtDNA as an outgroup to that of the humans. Furthermore, among the modern human mtDNAs, nine and eight African sequences were found to branch off on the first and the second branch after the Neandertal, respectively. These branches were supported by 91% and 92% of quartets, respectively.
|
Dates of Divergences.
For the estimation of the ages of MRCAs
of different groups of mtDNAs, the observed nucleotide differences were
corrected for multiple substitutions by using the Tamura-Nei algorithm
(17). The resulting genetic distances and the estimated age of the
modern human-chimpanzee split of 4-5 million years (22, 23) were used
to calculate the substitution rate of 0.94 × 107 substitutions per site per year per lineage
with 5.92 × 108 and 1.38 × 107 as the lower and upper confidence limits.
These estimates are in reasonable agreement with previous rate
estimations for the mtDNA control region (32, 33). Using these rates,
the age of the MRCA of the Neandertal and modern human mtDNAs was
estimated to be 465,000 years, with confidence limits of 317,000 and
741,000 years. This age is significantly older than that of the MRCA of modern human mtDNAs, which, by the same procedure, was determined to be
163,000 years, with 111,000 and 260,000 years as confidence limits.
Finally, the age of the MRCA of the mtDNAs of the seven chimpanzees and
the two bonobos was calculated as 2,844,000 years (confidence limits:
1,940,000 and 4,534,000 years).
Relative Divergence Between Neandertals and Humans. In western Europe, Neandertals and modern humans coexisted from approximately 40,000 years ago to less than 30,000 years ago (34). The implications of that coexistence in terms of culture and genetic relationships are a matter of debate. The results presented here indicate that the mtDNA gene pools of these two hominid forms had diverged for a substantial time before they came into contact. To put the extent of genetic differentiation that had resulted into perspective, a useful comparison may be the differentiation found today among chimpanzees and bonobos. The number of differences between the Neandertal and modern humans is 35.5 ± 2.3, about half that between chimpanzees and bonobos (75.7 ± 4.6). Unfortunately, HVRII sequences are not available for different subspecies of chimpanzees. However, if the analysis is confined to 312 bp of HVRI, the average difference between modern humans and the Neandertal is 25.6 ± 2.2, whereas that among 19 bonobos is 17.7 ± 8.5, among 10 central chimpanzees (Pan troglodytes troglodytes) is 14.6 ± 8.1, among 25 western chimpanzees (P. troglodytes verus) is 21.8 ± 9.7, and among 108 eastern chimpanzees (P. troglodytes schweinfurthii) is 7.9 ± 3.0. The observed differences between the subspecies varies from 19.7 ± 2.9 between central and eastern chimpanzees and 36.2 ± 6.1 and 33.0 ± 4.5 between western and central, and western and eastern chimpanzees, respectively. Thus, the average observed difference between the Neandertal mtDNA and the mtDNA of modern humans exceeds that occurring within chimpanzee subspecies and within bonobos, but is less than what is found between two of three pairwise comparisons between currently recognized subspecies of chimpanzees. When the differences are corrected for multiple substitutions, this general situation remains unchanged. However, mtDNA sequences from more Neandertal individuals are needed to obtain a better understanding of the extent of separation between the mtDNA gene pools of Neandertals and modern humans.
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CONCLUSIONS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS AND DISCUSSION
CONCLUSIONS
REFERENCES
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The divergence of the Neandertal mtDNA from the line leading to the contemporary human mtDNA gene pool is almost 3-fold older than the deepest divergence among contemporary human mtDNAs. The extent of sequence divergence exceeds that found within current chimpanzee subspecies. This shows that the Neandertal mtDNA and the human ancestral mtDNA gene pool have evolved as separate entities for a substantial period of time and gives no support to the notion that Neandertals should have contributed mtDNA to the modern human gene pool.
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ACKNOWLEDGEMENTS |
|---|
We are indebted to F. G. Zehnder and H.-E. Joachim (Rheinisches Landesmuseum Bonn) for permission to remove samples, to I. Boschi and V. Pascali for unpublished human mtDNA sequences, to P. Gagneux and U. Gerloff for unpublished chimpanzee and bonobo mtDNA sequences, to C. Capelli, S. Meyer, K. Strimmer, L. Vigilant, A. von Haeseler, and W. Schartau for discussion and technical help, and to the Boehringer-Ingelheim Fonds and the Deutsche Forschungsgemeinschaft for financial support.
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ABBREVIATIONS |
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HVRI and HVRII, first and second hypervariable region, respectively; MRCA, most recent common ancestor.
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FOOTNOTES |
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§ To whom reprint requests should be addressed. e-mail: paabo{at}eva.mpg.de.
This paper was submitted directly (Track II) to the Proceedings Office.
Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AF142095).
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ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS AND DISCUSSION
CONCLUSIONS
REFERENCES
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| 1. | Stringer, C. & McKie, R. (1996) African Exodus (Random House, London). |
| 2. | Wolpoff, M. & Caspari, R. (1997) Race and Human Evolution (Simon & Schuster, New York). |
| 3. | Schmitz, R. W., Pieper, P., Bonte, W. & Krainitzki, H. (1995) in Advances in Forensic Sciences, Forensic Odontology, eds. Jacob, B. & Bonte, W. (Köster, Berlin), Vol. 7, pp. 42-44. |
| 4. | Schmitz, R. W. (1996) Doctoral thesis (University of Cologne, Germany). |
| 5. | Krings, M., Stone, A., Schmitz, R.-W., Krainitzki, H., Stoneking, M. & Pääbo, S. (1997) Cell 90, 19-30 [CrossRef][ISI][Medline] . |
| 6. | Nordborg, M. (1998) Am. J. Hum. Genet. 63, 1237-1240 [CrossRef][ISI][Medline] . |
| 7. | Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., et al. (1981) Nature (London) 290, 457-474 [CrossRef][Medline] . |
| 8. |
Handt, O., Meyer, S. & von Haeseler, A.
(1998)
Nucleic Acids Res.
26,
126-129
|
| 9. | Arnason, U., Xu, X. & Gullberg, A. (1996) J. Mol. Evol. 42, 145-152 [CrossRef][ISI][Medline] . |
| 10. |
Foran, D. R., Hixson, J. E. & Brown, W. M.
(1988)
Nucleic Acids Res.
16,
5841-5861
|
| 11. | Goldberg, T. L. & Ruvolo, M. (1997) Mol. Biol. Evol. 14, 976-984 [Abstract]. |
| 12. |
Horai, S., Hayasaka, K., Kondo, R., Tsugane, K. & Takahata, N.
(1995)
Proc. Natl. Acad. Sci. USA
92,
532-536
|
| 13. | Kocher, T. D. & Wilson, A. C. (1991) in Evolution of Life: Fossils, Molecules and Culture, eds. Osawa, S. & Honjo, T. (Springer, Tokyo), pp. 391-413. |
| 14. |
Morin, P. A., Moore, J. J., Chakraborty, R., Jin, L., Goodall, J. & Woodruff, D. S.
(1994)
Science
265,
1193-1201
|
| 15. | Strimmer, K. & von Haeseler, A. (1996) J. Mol. Evol. 13, 964-969 . |
| 16. | Felsenstein, J. (1994) PHYLIP (University of Washington, Seattle), Version 3.5. |
| 17. | Saitou, N. & Nei, M. (1987) Mol. Biol. Evol. 4, 406-425 [Abstract]. |
| 18. |
Strimmer, K. & von Haeseler, A.
(1997)
Proc. Natl. Acad. Sci. USA
94,
6815-6819
|
| 19. | Tamura, K. & Nei, M. (1993) J. Mol. Evol. 10, 512-526 . |
| 20. | Wakeley, J. (1993) J. Mol. Evol. 37, 613-623 [ISI][Medline] . |
| 21. | Yang, Z. (1994) J. Mol. Evol. 39, 306-314 [CrossRef][ISI][Medline] . |
| 22. | Adachi, J. & Hasegawa, M. (1995) J. Mol. Evol. 40, 622-628 [CrossRef][ISI][Medline] . |
| 23. | Takahata, N., Satta, Y. & Klein, J. (1995) Theor. Popul. Biol. 48, 198-221 [CrossRef][ISI][Medline] . |
| 24. | King, W. (1864) Q. J. Sci. 1, 88-97 . |
| 25. |
Höss, M., Jaruga, P., Zastawny, T. H., Dizdaroglu, M. & Pääbo, S.
(1996)
Nucleic Acids Res.
24,
1304-1307
|
| 26. | Zischler, H., Höss, M., Handt, O., von Haeseler, A., van der Kuyl, A. C., Goudsmit, J. & Pääbo, S. (1995) Science 268, 1193 . |
| 27. | Smith, F. H., Falsetti, A. B. & Donelly, S. M. (1989) Yearbook Phys. Anthropol. 32, 35-68 [CrossRef][ISI]. |
| 28. | Wolpoff, M. (1998) Evol. Anthropol. 7, 1-3 . |
| 29. | Cann, R. L., Stoneking, M. & Wilson, A. C. (1987) Nature (London) 325, 31-36 . |
| 30. |
Vigilant, L., Stoneking, M., Harpending, H., Hawkes, K. & Wilson, A. C.
(1991)
Science
253,
1503-1507
|
| 31. | Zischler, H., Geisert, H., von Haeseler, A. & Pääbo, S. (1995) Nature (London) 378, 489-492 [CrossRef][Medline] . |
| 32. | Jazin, E., Soodyall, H., Jalonen, P., Lindholm, E., Stoneking, M. & Gyllensten, U. (1998) Nat. Genet. 18, 109-110 [CrossRef][ISI][Medline] . |
| 33. |
Ward, R. H., Frazier, B. L., Dew-Jager, K. & Pääbo, S.
(1991)
Proc. Natl. Acad. Sci. USA
88,
8720-8724
|
| 34. | Hublin, J.-J., Barosso Ruiz, C., Medina Lara, P., Fontugne, M. & Reyss, J.-L. (1995) C. R. Acad. Sci. Paris 321, 931-937 . |
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T. R. DISOTELL Molecular Anthropology and Race Ann. N.Y. Acad. Sci., December 1, 2000; 925(1): 9 - 24. [Abstract] [Full Text] [PDF]
|
|
|
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|
|
F. H. Smith, E. Trinkaus, P. B. Pettitt, I. Karavanic, and M. Paunovic Direct radiocarbon dates for Vindija G1 and Velika Pec'ina Late Pleistocene hominid remains PNAS, October 26, 1999; 96(22): 12281 - 12286. [Abstract] [Full Text] [PDF]
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