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Enamel hypoplasia in deciduous teeth of great apes: do differences in defect prevalence imply differential levels of physiological stress?

This paper presents new data on enamel hypoplasia in the deciduous canine teeth of great apes. The enamel defect under consideration is known as localized hypoplasia of primary canines (LHPC), and is characterized by an area of thin or missing enamel on the labial surface of deciduous canine teeth (Skinner [1986a] Am. J. Phys. Anthropol. 69:59-69). Goals of this study are: 1) to determine if significant differences in the frequency of LHPC occur among three genera of great apes, and 2) to evaluate variation in LHPC prevalence among great apes as evidence of differential physiological stress. Infant and juvenile apes with deciduous teeth were examined at the Cleveland Museum of Natural History (n = 100) and at the Smithsonian Institution, National Museum of Natural History (n = 36). Deciduous teeth were observed under oblique incandescent light, with the naked eye and with a 10x hand lens. Enamel hypoplasia was scored using Federation Dentaire International (FDI)-Defects of Dental Enamel (DDE) standards. Hypoplasias were recorded by drawing defect location and size on a dental chart, and by measuring defect size and location with Helios needlepoint dial calipers. The prevalence of LHPC is reported by genus and sex, using two approaches: 1) the frequency of affected individuals-those having one or more deciduous canine teeth scored positive for LHPC; and 2) the number of canine teeth scored positive for LHPC as a percentage of all canine teeth observed. Variation in defect size and location will be described elsewhere. Localized hypoplasia of primary canine teeth was found in 62.5% of 128 individual apes, and in 45.5% of 398 great ape deciduous canines. As in humans, LHPC is the most common form of enamel hypoplasia in deciduous teeth of great apes, while LEH is rare or absent. The distribution and pattern of expression of LHPC in great apes is similar to that described in humans: side differences are not significant, but mandibular canines exhibit the defect two to five times more often than maxillary canine teeth. Differences in LHPC prevalence by sex are small and not significant. Intergeneric differences are large and non-random: chimpanzees (Pan) exhibit a significantly lower frequency of LHPC (22%, n = 50) by individual count, than either the orangutan (Pongo, 88.0%, n = 25) or the gorilla (Gorilla, 88.7%, n = 53). Tooth count prevalences exhibit a similar pattern of variation and are also statistically significant. These findings suggest that large bodied great apes (gorilla and orangutan) may be under greater physiological stress during perinatal and early postnatal development than the chimpanzee. The size, position, and timing of LHPC lesions are currently under analysis and may yield more insight into the etiological origin of this enamel defect.

Animals↗

Gross anatomy of the pancreatic lobes and ducts in six breeds of domestic ducks and six species of wild ducks in China.

A previously unreported pancreatic duct was found by Liu (1989) in Pekin ducks. This duct has now been consistently found in six breeds of domestic ducks and six species of wild ducks in China. For purposes of Nomina Anatomica Avium it is hereby called the 'first pancreatic duct' (Ductus pancreaticus primus) since it enters the duodenum at or near the flexure where the descending duodenum becomes the ascending duodenum. All other pancreatic ducts enter the duodenum later, closer to where it joins the jejunum. This first pancreatic duct drains the caudal extremity of the dorsal lobe of the pancreas and can be easily exteriorized for experimental purposes. Within the parenchyma of the dorsal lobe of the pancreas this duct communicates with the dorsal pancreatic duct. In the present study of the gross anatomy of the pancreatic lobes of domestic and wild Chinese ducks we describe and illustrate variations in position and number of all biliary and pancreatic ducts.

Animals↗

Variations in uterine innervation during the estrous cycle in rat.

Uterine innervation undergoes profound remodeling during puberty, pregnancy, and after parturition. However, the extent to which uterine innervation may change during the estrous cycle is uncertain. The objective of the present study was to determine whether nerve fiber density of the uterine horn is altered during the estrous cycle and, if so, which subpopulations are affected. Immunostaining for the pan-neuronal marker protein gene product (PGP) 9.5 revealed fibers within the vascular zone, myometrium, and endometrium, with greater density in the ovarian and cervical regions than in the middle. In most structures, nerve density was reduced during estrus. This could not be accounted for by increased target volume, as the reduction in longitudinal muscle innervation persisted after correction for changes in target size. Immunostaining for vasoactive intestinal polypeptide-immunoreactive parasympathetic nerves revealed fibers associated predominantly with the vascular zone and circular muscle within the cervical region. No cyclical variation was detected. Calcitonin gene-related peptide-immunoreactive nerves were present within all structures, and density was highest at the ovarian end. These fibers also did not vary significantly through estrous. Dopamine beta-hydroxylase-immunoreactive sympathetic nerves innervated all structures, with greater density in the ovarian end. These fibers were reduced substantially during estrus, but the decline was also significant in proestrus, thus preceding that detected by using the pan-neuronal marker. We conclude that the estrous cycle in rat is accompanied by structural remodeling of sympathetic nerves by way of retraction or degeneration of terminal fibers during estrus. The structural loss of the terminal axon apparently is preceded by depletion of catecholamine-synthesizing enzyme.

Animals↗

mtDNA polymorphism in East Asian Populations, with special reference to the peopling of Japan.

Nucleotide sequences of the major noncoding (D-loop) region of human mtDNA from five East Asian populations including mainland Japanese, Ainu, Ryukyuans, Koreans, and Chinese were analyzed. On the basis of a comparison of 482-bp sequences in 293 East Asians, 207 different sequence types were observed. Of these, 189 were unique to their respective populations, whereas 18 were shared between two or three populations. Among the shared types, eight were found in common between the mainland Japanese and Koreans, which is the largest number in the comparison. The intergenic COII/tRNA(Lys) 9-bp deletion was observed in every East Asian population with varying frequencies. The D-loop sequence variation suggests that the deletion event occurred only once in the ancestry of East Asians. Phylogenetic analysis revealed that East Asian lineages were classified into at least 18 monophyletic clusters, though lineages from the five populations were completely intermingled in the phylogenetic tree. However, we assigned 14 of the 18 clusters for their specificity on the basis of the population from which the maximum number of individuals in each cluster was derived. Of note is the finding that 50% of the mainland Japanese had continental specificity in which Chinese or Koreans were dominant, while < 20% of either Ryukyuans or Ainu possessed continental specificity. Phylogenetic analysis of the entire human population revealed the closest genetic affinity between the mainland Japanese and Koreans. Thus, the results of this study are compatible with the hybridization model on the origin of modern Japanese. It is suggested that approximately 65% of the gene pool in mainland Japanese was derived from the continental gene flow after the Yayoi Age.

Asian People↗

Bathymetric and geographic population structure in the pan-Atlantic deep-sea bivalve Deminucula atacellana (Schenck, 1939).

The deep-sea soft-sediment environment hosts a diverse and highly endemic fauna of uncertain origin. We know little about how this fauna evolved because geographic patterns of genetic variation, the essential information for inferring patterns of population differentiation and speciation are poorly understood. Using formalin-fixed specimens from archival collections, we quantify patterns of genetic variation in the protobranch bivalve Deminucula atacellana, a species widespread throughout the Atlantic Ocean at bathyal and abyssal depths. Samples were taken from 18 localities in the North American, West European and Argentine basins. A hypervariable region of mitochondrial 16S rDNA was amplified by polymerase chain reaction (PCR) and sequenced from 130 individuals revealing 21 haplotypes. Except for several important exceptions, haplotypes are unique to each basin. Overall gene diversity is high (h = 0.73) with pronounced population structure (Phi(ST) = 0.877) and highly significant geographic associations (P < 0.0001). Sequences cluster into four major clades corresponding to differences in geography and depth. Genetic divergence was much greater among populations at different depths within the same basin, than among those at similar depths but separated by thousands of kilometres. Isolation by distance probably explains much of the interbasin variation. Depth-related divergence may reflect historical patterns of colonization or strong environmental selective gradients. Broadly distributed deep-sea organisms can possess highly genetically divergent populations, despite the lack of any morphological divergence.

Animals↗

Phylogeography of Varicorhinus barbatulus (Cyprinidae) in Taiwan based on nucleotide variation of mtDNA and allozymes.

The phylogeographical patterns and population genetic structures of Varicorhinus barbatulus in Taiwan were investigated based on genetic diversity of 34 allozyme loci and nucleotide sequences of 3' end of the cytochrome b gene, tRNA genes, D-loop control region, and the 5' end of the 12S rRNA of mtDNA. Allozyme and mtDNA analyses revealing evident geographical structuring suggest limited gene flow between populations (F(ST)=0.511 and 0.791, respectively). Low genetic variability within populations (P=5.56%; He=0.018) based on allozymes and significantly negative Tajima's D statistics based on mtDNA suggest that most populations in Taiwan may have originated from a small number of founders followed by demographic expansion. The gene genealogy of mtDNA identified six lineages corresponding to major drainages that were separated by the geological barriers due to vicariant events. A minimum spanning network based on nucleotide substitutions reflects divergence from populations of the Miao-li Plateau to northern and southern regions of the island. In contrast to a previous hypothesis that suggests an early invasion to eastern part of Taiwan prior to the lifting of central mountain range some one million years ago, the mtDNA genealogy and molecular dating reveal very recent colonization of the eastern population. Nested clade analyses revealing significant associations between genetic structure and geographical division identify past fragmentation and range expansion as major phylogeographical events that shaped the geographical distribution of this species in Taiwan.

Animals↗

Quantifying trabecular orientation in the pelvic cancellous bone of modern humans, chimpanzees, and the Kebara 2 Neanderthal.

The adaptive nature of bone lies in its ability to respond to the environment by conforming and reshaping itself constantly to accommodate life-time stresses experienced throughout daily activities. In order to keep strains within the bone as uniform and isotropic as possible, the trabecular orientation is determined by forces acting on the bone through adaptive remodeling. Hence, the preserved structure of bones may contain direct information about the forces they may have undergone. Some authors (Correnti [1952], Atti Acc Naz Lincei 12:518-523, [1955] Riv Antrop 42:289-336; Macchiarelli et al. [1999] J Hum Evol 36:211-232, [2001] Cambridge, UK: Cambridge University Press) have described in detail the trabecular systems of the hip bone in different primate species and have identified a gait-related system above the acetabulum with substantial differences across species (Macchiarelli et al. [1999]; Rook et al. [1999] Proc Natl Acad Sci USA 96:8875-8879). The aim of this study was to quantify trabecular orientation above the acetabulum to test the hypothesis that hominoid biomechanical behavior is recorded in the cancellous bone. The pelvic bones of 23 archaeological adult modern humans (12 females, 11 males), 20 adult Pan troglodytes (10 females, 10 males), and one adult male Neanderthal were radiographed and digitized. Fast Fourier transforms (FFTs) of the regions of interest in the corpus of the ilium were performed, with the angular distribution of the trabeculae quantified. All species displayed a constant and periodic orthogonal arrangement in the trabeculae with differences in the pattern of dominance between the arcades oriented along the 0 degrees or the 90 degrees axes. The variation in the FFT spectrum between species is discussed in the light of distinctive biomechanical features.

Animals↗

The simian T-lymphotropic virus STLV-PP1664 from Pan paniscus is distinctly related to HTLV-2 but differs in genomic organization.

We have isolated a highly divergent simian T-lymphotropic virus, STLV-PP1664, from a wild-caught bonobo (Pan paniscus). Previous phylogenetic analysis suggested that this virus represents an additional type of STLV but this has now become a matter of discussion. We have now obtained and analyzed the entire genome of STLV-PP1664. All major genes and their corresponding viral messengers were identified. Sequence comparison and phylogenetic analysis indicated that this virus, together with the closely related panp isolate, belongs to an early lineage within the PTLV-2 clade, differing from HTLV-2 by about 25%. In contrast to the HTLV-1 and HTLV-2 LTR, only two 21-bp repeats instead of three were found in the STLV-PP1664 LTR. Additional messengers, resulting from alternative splicing, potentially encode five different accessory proteins from open reading frames in the pX region: prorfI, porfII, ptorfV', and two isoforms of Rex. The amino acid sequences of these proteins are only distinctly related to the accessory proteins from HTLV-2. These data suggest a different genomic organization of the STLV-PP1664 pX region than that of HTLV-2. We conclude that STLV-PP1664, although related to HTLV-2, has some distinct features in the LTR and the pX regions, the impact of which needs further investigation. Although arguments pro and contra a distinct classification are nearly equally balanced, we propose to classify this virus as an STLV-2, designated STLV-2PP1664.

Amino Acid Sequence↗

SSADH variation in primates: intra- and interspecific data on a gene with a potential role in human cognitive functions.

In the present study we focus on the nucleotide and the inferred amino acid variation occurring in humans and other primate species for mitochondrial NAD(+)-dependent succinic semialdehyde dehydrogenase, a gene recently supposed to contribute to cognitive performance in humans. We determined 2527 bp of coding, intronic, and flanking sequences from chimpanzee, bonobo, gorilla, orangutan, gibbon, and macaque. We also resequenced the entire coding sequence on 39 independent chromosomes from Italian families. Four variable coding sites were genotyped in additional populations from Europe, Africa, and Asia. A test for constancy of the nonsynonymous vs. synonymous rates of nucleotide changes revealed that primates are characterized by largely variable d(N)/d(S) ratios. On a background of strong conservation, probably controlled by selective constraints, the lineage leading to humans showed a ratio increased to 0.42. Human polymorphic levels fall in the range reported for other genes, with a pattern of frequency and haplotype structure strongly suggestive of nonneutrality. The comparison with the primate sequences allowed inferring the ancestral state at all variable positions, suggesting that the c.538(C) allele and the associated functional variant is indeed a derived state that is proceeding to fixation. The unexpected pattern of human polymorphism compared to interspecific findings outlines the possibility of a recent positive selection on some variants relevant to new cognitive capabilities unique to humans.

Adaptation, Biological↗

Ultrastructural allelic variation in HLA-DQB1 promoter elements.

Sequence variation among HLA class II promoter elements may contribute to functional differences in transcriptional regulation of different class II alleles. In addition to influencing the binding sites for nuclear transcription factors, promoter polymorphism may also alter intrinsic structural properties of the DNA strands, such as conformation and curvature, which influence the formation of stable transcription complexes. We used SSCP analysis of PCR-amplified promoter regions from the DQB1 locus to evaluate conformational polymorphism within DQ alleles. Distinct electrophoretic migration patterns of the SSCP products were detected for six DQB1 alleles; analysis of the DQB1*0302 promoter, known to be associated with type 1 diabetes, showed no SSCP differences between IDDM patients and normal controls. Using computer modeling based on a "nearest-neighbor" energy of predicted curvature theory, we examined the effect of allelic promoter region sequence polymorphism on the predicted curvature of double-stranded DNA, and found distinct allelic differences in predicted DNA curvature, both in transcriptional consensus binding sites and in regions located between binding sites. These data are consistent with a model in which intrinsic sequence variation in the promoter region results in ultrastructural differences which may influence DNA bending and interactions with multimeric DNA-protein transcription complexes.

Alleles↗

Time of symptom onset of eight common medical emergencies.

Specific time periods of the day may be associated with different frequencies of symptom onset in different diseases. The purpose of the current study was to examine times of symptom onset in eight commonly encountered emergent conditions--cerebral infarction, cerebral hemorrhage, transient ischemic attacks, cardiac dysrhythmias, angina pectoris, acute myocardial infarction, gastrointestinal bleeding, and acute asthma. Data from 4554 cases were retrospectively reviewed. Symptom onset frequency curve diagrams were derived, illustrating peak hours of symptom presentation for each of the eight emergent conditions. Hormonal and metabolic factors that may be related to diurnal variations in symptom onset of the eight diseases are briefly discussed.

Acute Disease↗

Grading xerostomia by physicians or by patients after intensity-modulated radiotherapy of head-and-neck cancer.

PURPOSE: To assess observer-based vs. patient self-reported scoring of xerostomia after intensity-modulated radiotherapy (IMRT) of head-and-neck (HN) cancer. METHODS: A total of 38 patients who had received IMRT for HN cancer underwent xerostomia evaluations 6 to 24 months after completion of therapy using three methods each time: (1) Grading by 3 observers according to the Radiotherapy Oncology Group/European Organization for Research and Therapy of Cancer (RTOG/EORTC) system; (2) patient self-reported validated xerostomia questionnaire (XQ); and (3) major salivary gland flow measurements. RESULTS: The interobserver agreement regarding the RTOG/EORTC grades was moderate: kappa-coefficient 0.54 (95% CI=0.31-0.76). The correlations between the average RTOG/EORTC grades and the salivary flow rates were not statistically significant. A trend for significant correlation was observed between these grades and the percent (relative to the pretherapy) nonstimulated salivary flow rates (p=0.07), but not with the percent stimulated flow rates. Better correlations were found between grading made more than the median time (15 min) after the last liquid sipping and the nonstimulated (but not the stimulated) flows compared with grading made shortly after sipping. In contrast, significant correlations were found between the XQ scores and the nonstimulated (p<0.005) and the stimulated (p<0.005) salivary flow rates, as well as with the percentages of the corresponding pretherapy values (p=0.002 and 0.038, respectively). No significant correlation was found between the RTOG/EORTC grades and the XQ scores. The observer-based grades underestimated the severity of xerostomia compared with the patient self-reported scores. CONCLUSIONS: Patient self-reported, rather than physician-assessed scores, should be the main end points in evaluating xerostomia.

Cross-Sectional Studies↗

Complete nucleotide sequence and viral envelope protein expression of a hepatitis B virus DNA derived from a hepatitis B surface antigen-seronegative patient.

An HBV strain isolated from a patient lacking conventional serological markers of HBV infection was characterized. The complete nucleotide sequence was determined following PCR amplification. Only 22 nucleotide substitutions were found relative to the reported sequence of the ayw subtype. Five of these point mutations in the preS/S and preC/C genes led to amino acid substitutions and, with one exception, were located in regions coding for antigenic determinants of viral envelope or capsid proteins. Eight amino acid substitutions were located in terminal protein and the spacer domain of the polymerase gene product. Despite these amino acid changes, transient expression of the preS2 and S envelope proteins in eucaryotic cells yielded viral proteins detectable in the culture medium with polyclonal and monoclonal anti-preS2 and -S antibodies. These data conclusively demonstrate persistent infection by HBV in subjects without HBV serological markers. The absence of conventional HBV serological markers is probably due to several factors: a low level of viral replication, some genetic modifications, as well as an abnormal immune response to the virus.

Animals↗

Genomic structure of the human prototype strain H of hepatitis C virus: comparison with American and Japanese isolates.

Genomic RNA from the human prototype strain H of the hepatitis C virus (HCV-H) has been molecularly cloned and sequenced. The HCV-H sequence reported consists of 9416 nucleotides including the 5' and 3' untranslated regions. HCV-H shows 96% amino acid identity with the American isolate HCV-1 but only 84.9% with the Japanese isolates HCV-J and HCV-BK. In addition to the hypervariable region (region V) previously identified in the putative E2 domain, three other variable domains were identified: region V1 (putative E1), region V2 (putative E2), and region V3 (putative NS5). These regions appear rather conserved (86-100%) among the American isolates (HCV-1 and HC-J1) or among various Japanese isolates (HCV-J, HCV-BK, HCV-JH, and HC-J4) but show striking heterogeneity when the two subgroups are compared (42-87.5% amino acid difference). A structural similarity between the 5'-terminal hairpin structure of HCV and of poliovirus was observed. This study further suggests the existence of at least two genomic subtypes of HCV and confirms a distant relationship between HCV and pestiviruses.

Amino Acid Sequence↗

Prevention of hepatitis C virus infection in chimpanzees by hyperimmune serum against the hypervariable region 1 of the envelope 2 protein.

The identification of the neutralization domains of hepatitis C virus (HCV) is essential for the development of an effective vaccine. Here, we show that the hypervariable region 1 (HVR1) of the envelope 2 (E2) protein is a critical neutralization domain of HCV. Neutralization of HCV in vitro was attempted with a rabbit hyperimmune serum raised against a homologous synthetic peptide derived from the HVR1 of the E2 protein, and the residual infectivity was evaluated by inoculation of HCV-seronegative chimpanzees. The source of HCV was plasma obtained from a patient (H) during the acute phase of posttransfusion non-A, non-B hepatitis, which had been titered for infectivity in chimpanzees. The anti-HVR1 antiserum induced protection against homologous HCV infection in chimpanzees, but not against the emergence of neutralization escape mutants that were found to be already present in the complex viral quasispecies of the inoculum. The finding that HVR1 can elicit protective immunity opens new perspectives for the development of effective preventive strategies. However, the identification of the most variable region of HCV as a critical neutralization domain poses a major challenge for the development of a broadly reactive vaccine against HCV.

Amino Acid Sequence↗