CD4 receptor diversity represents an ancient protection mechanism against primate lentiviruses.

Infection with human and simian immunodeficiency viruses (HIV/SIV) requires binding of the viral envelope glycoprotein (Env) to the host protein CD4 on the surface of immune cells. Although invariant in humans, the Env binding domain of the chimpanzee CD4 is highly polymorphic, with nine coding variants circulating in wild populations. Here, we show that within-species CD4 diversity is not unique to chimpanzees but found in many African primate species. Characterizing the outermost (D1) domain of the CD4 protein in over 500 monkeys and apes, we found polymorphic residues in 24 of 29 primate species, with as many as 11 different coding variants identified within a single species. D1 domain amino acid replacements affected SIV Env-mediated cell entry in a single-round infection assay, restricting infection in a strain- and allele-specific fashion. Several identical CD4 polymorphisms, including the addition of N-linked glycosylation sites, were found in primate species from different genera, providing striking examples of parallel evolution. Moreover, seven different guenons (Cercopithecus spp.) shared multiple distinct D1 domain variants, pointing to long-term trans-specific polymorphism. These data indicate that the HIV/SIV Env binding region of the primate CD4 protein is highly variable, both within and between species, and suggest that this diversity has been maintained by balancing selection for millions of years, at least in part to confer protection against primate lentiviruses. Although long-term SIV-infected species have evolved specific mechanisms to avoid disease progression, primate lentiviruses are intrinsically pathogenic and have left their mark on the host genome.

The Genome of the Endangered Dryas Monkey Provides New Insights into the Evolutionary History of the Vervets.

Genomic data can be a powerful tool for inferring ecology, behavior, and conservation needs of highly elusive species, particularly, when other sources of information are hard to come by. Here, we focus on the Dryas monkey (Cercopithecus dryas), an endangered primate endemic to the Congo Basin with cryptic behavior and possibly <250 remaining adult individuals. Using whole-genome sequencing data, we show that the Dryas monkey represents a sister lineage to the vervets (Chlorocebus sp.) and has diverged from them ∼1.4 Ma with additional bidirectional gene flow ∼750,000-∼500,000 years ago that has likely involved the crossing of the Congo River. Together with evidence of gene flow across the Congo River in bonobos and okapis, our results suggest that the fluvial topology of the Congo River might have been more dynamic than previously recognized. Despite the presence of several homozygous loss-of-function mutations in genes associated with sperm mobility and immunity, we find high genetic diversity and low levels of inbreeding and genetic load in the studied Dryas monkey individual. This suggests that the current population carries sufficient genetic variability for long-term survival and might be larger than currently recognized. We thus provide an example of how genomic data can directly improve our understanding of highly elusive species.

Morphological analysis of new Dryas Monkey specimens from the Central Congo Basin: Taxonomic considerations and an emended diagnosis.

OBJECTIVES: The little known guenon Cercopithecus dryas has a controversial taxonomic history with some recognizing two taxa (C. dryas and C. salongo) instead of one. New adult specimens from the TL2 region of the central Congo Basin allow further assessment of C. dryas morphology and, along with CT scans of the juvenile holotype, provide ontogenetically stable comparisons across all C. dryas and "C. salongo" specimens for the first time. MATERIALS AND METHODS: The skins and skulls of two newly acquired C. dryas specimens, male YPM MAM 16890 and female YPM MAM 17066, were compared to previously described C. dryas and "C. salongo" specimens, along with a broader guenon comparative sample (cranial sample n = 146, dental sample n = 102). Qualitative and quantitative assessments were made on the basis of commonly noted pelage features as well as craniodental characters in the form of shape ratios and multivariate discriminant analyses. RESULTS: All C. dryas specimens, including the TL2 adults, are comparatively small in overall cranial size, have relatively small I1 s, and display tall molar cusps; these osteological characters, along with pelage features, are shared with known "C. salongo" specimens. Discriminant analyses of dental features separate C. dryas/salongo specimens from all other guenons. DISCUSSION: In addition to pelage-based evidence, direct osteological evidence suggests "C. salongo" is a junior synonym of C. dryas. Combined with molecular analyses suggesting C. dryas is most closely related to Chlorocebus spp., we emend the species diagnosis and support its transfer to Chlorocebus or possibly a new genus to reflect its distinctiveness.

A natural history of Chlorocebus dryas from camera traps in Lomami National Park and its buffer zone, Democratic Republic of the Congo, with notes on the species status of Cercopithecus salongo.

The natural history and taxonomic status of two central African primates, Cercopithecus dryas and Cercopithecus salongo have long been in question. Recent studies confirmed that C. dryas is a basal member of the savanna monkey clade, and that it prefers dense undergrowth in lowland rainforest. While these studies advanced our knowledge of this enigmatic species, key aspects of its natural history remain poorly documented. Furthermore, the lack of a field study that documents pelage patterns of both sexes and different age classes of C. dryas has led to a disagreement over the validity of C. salongo as a sister taxon to C. dryas. Using the results of two multi-strata camera trap surveys in Lomami National Park (Democratic Republic of the Congo) and its buffer zone, we conducted a third survey in the understory of degraded forest to accumulate videos of C. dryas/salongo. We used these videos to test the hypothesis that C. dryas and C. salongo are synonymous, and to assess the species' group composition, density, behavior and vocalizations. Camera traps revealed an ontogenetic change in pelage pattern that supports the view that C. salongo is the adult of C. dryas. Videos revealed that adult males develop a blue perineum and scrotum, and a red subcaudal patch, similar to other savanna monkeys. We provide a preliminary assessment of C. dryas' group composition, density, behavior, and vocalizations. This long-overlooked monkey is an exceptional member of the Chlorocebus clade, and all aspects of its biology require further investigation.

Skeletal morphology of the lesula (Cercopithecus lomamiensis) and the evolution of guenon locomotor behavior.

OBJECTIVES: The guenons (tribe Cercopithecini) are a diverse and primarily arboreal radiation of Old World monkeys from Africa. However, preliminary behavioral observations of the lesula (Cercopithecus lomamiensis), a little-known guenon species described in 2012, report it spending substantial amounts of time on the ground. New specimens allow us to present the first description of lesula postcranial morphology and apply a comparative functional morphology approach to supplement our knowledge of its locomotor behavior. MATERIALS AND METHODS: To infer the substrate use preferences of the lesula, 22 postcranial variables correlated with locomotion were assessed in a sample of 151 adult guenon specimens, including two C. lomamiensis. Using multivariate statistical analyses, we predict the amount of time the lesula spends on the ground relative to the comparative sample. RESULTS: Results suggest that the lesula spends nearly half its time on the ground, and the two available individuals were classified as semiterrestrial and terrestrial with strong support. Comparisons with two outgroup cercopithecid taxa (Colobus guereza and Macaca mulatta) demonstrate that, as a group, guenons retain signals of a generalized, semiterrestrially adapted postcranium compared to specialized arboreal cercopithecids. DISCUSSION: These results corroborate preliminary behavioral observations of the lesula as a semiterrestrial to terrestrial primate and imply multiple evolutionary transitions in substrate use among the guenon radiation. A broader view of cercopithecoid evolution suggests that a semiterrestrial ancestor for extant guenons is more parsimonious than an arboreal one, indicating that the arboreal members of the group are probably recently derived from a more semiterrestrial ancestor.

Dissection-enabled scaffold-assisted resection (DeSCAR): a novel technique for resection of residual or non-lifting GI neoplasia of the colon (with video).

BACKGROUND AND AIMS: As a result of previous manipulation or submucosal invasion, GI lesions referred for EMR frequently have flat areas of visible tissue that cannot be snared. Current methods for treating residual tissue may lead to incomplete eradication or not allow complete tissue sampling for histologic evaluation. Our aim is to describe dissection-enabled scaffold-assisted resection (DeSCAR), a new technique combining circumferential ESD with EMR for removal of superficial non-lifting or residual "islands" with suspected submucosal involvement/fibrosis. METHODS: From 2015 to 2017, lesions referred for EMR were retrospectively reviewed. Cases were identified where lifting and/or snaring of the lesion was incomplete and the DeSCAR technique was undertaken. Cases were reviewed for location, previous manipulation, rates of successful hybrid resection, and adverse events. RESULTS: Twenty-nine lesions underwent DeSCAR because of non-lifting or residual "islands" of tissue. Fifty-two percent of the patients were male and 48% were female; average age was 66 years (standard deviation ±9.9 years). Lesions were located in the cecum (n = 10), right side of the colon (n = 12), left side of the colon (n = 4), and rectum (n = 3). Average size was 31 mm (standard deviation ±20.6 mm). Previous manipulation had occurred in 28 of 29 cases (83% biopsy, 34% resection attempt, 52% tattoo). The technical success rate for resection of non-lifting lesions was 100%. There was one episode of delayed bleeding but no other adverse events. CONCLUSIONS: DeSCAR is a feasible and safe alternative to argon plasma coagulation and avulsion for the endoscopic management of non-lifting or residual GI lesions, providing en bloc resection of tissue for histologic review. Further studies are needed to demonstrate long-term eradication and for comparison with other methods.

Dietary changes of large herbivores in the Turkana Basin, Kenya from 4 to 1 Ma.

A large stable isotope dataset from East and Central Africa from ca. 30 regional collection sites that range from forest to grassland shows that most extant East and Central African large herbivore taxa have diets dominated by C4 grazing or C3 browsing. Comparison with the fossil record shows that faunal assemblages from ca. 4.1-2.35 Ma in the Turkana Basin had a greater diversity of C3-C4 mixed feeding taxa than is presently found in modern East and Central African environments. In contrast, the period from 2.35 to 1.0 Ma had more C4-grazing taxa, especially nonruminant C4-grazing taxa, than are found in modern environments in East and Central Africa. Many nonbovid C4 grazers became extinct in Africa, notably the suid Notochoerus, the hipparion equid Eurygnathohippus, the giraffid Sivatherium, and the elephantid Elephas. Other important nonruminant C4-grazing taxa switched to browsing, including suids in the lineage Kolpochoerus-Hylochoerus and the elephant Loxodonta. Many modern herbivore taxa in Africa have diets that differ significantly from their fossil relatives. Elephants and tragelaphin bovids are two groups often used for paleoecological insight, yet their fossil diets were very different from their modern closest relatives; therefore, their taxonomic presence in a fossil assemblage does not indicate they had a similar ecological function in the past as they do at present. Overall, we find ecological assemblages of C3-browsing, C3-C4-mixed feeding, and C4-grazing taxa in the Turkana Basin fossil record that are different from any modern ecosystem in East or Central Africa.

Stable isotope-based diet reconstructions of Turkana Basin hominins.

Hominin fossil evidence in the Turkana Basin in Kenya from ca. 4.1 to 1.4 Ma samples two archaic early hominin genera and records some of the early evolutionary history of Paranthropus and Homo. Stable carbon isotopes in fossil tooth enamel are used to estimate the fraction of diet derived from C3 or C4 resources in these hominin taxa. The earliest hominin species in the Turkana Basin, Australopithecus anamensis, derived nearly all of its diet from C3 resources. Subsequently, by ca. 3.3 Ma, the later Kenyanthropus platyops had a very wide dietary range--from virtually a purely C3 resource-based diet to one dominated by C4 resources. By ca. 2 Ma, hominins in the Turkana Basin had split into two distinct groups: specimens attributable to the genus Homo provide evidence for a diet with a ca. 65/35 ratio of C3- to C4-based resources, whereas P. boisei had a higher fraction of C4-based diet (ca. 25/75 ratio). Homo sp. increased the fraction of C4-based resources in the diet through ca. 1.5 Ma, whereas P. boisei maintained its high dependency on C4-derived resources.

Widespread extinctions of co-diversified primate gut bacterial symbionts from humans.

Humans and other primates harbour complex gut bacterial communities that influence health and disease, but the evolutionary histories of these symbioses remain unclear. This is partly due to limited information about the microbiota of ancestral primates. Here, using phylogenetic analyses of metagenome-assembled genomes (MAGs), we show that hundreds of gut bacterial clades diversified in parallel (that is, co-diversified) with primate species over millions of years, but that humans have experienced widespread losses of these ancestral symbionts. Analyses of 9,460 human and non-human primate MAGs, including newly generated MAGs from chimpanzees and bonobos, revealed significant co-diversification within ten gut bacterial phyla, including Firmicutes, Actinobacteriota and Bacteroidota. Strikingly, ~44% of the co-diversifying clades detected in African apes were absent from available metagenomic data from humans and ~54% were absent from industrialized human populations. In contrast, only ~3% of non-co-diversifying clades detected in African apes were absent from humans. Co-diversifying clades present in both humans and chimpanzees displayed consistent genomic signatures of natural selection between the two host species but differed in functional content from co-diversifying clades lost from humans, consistent with selection against certain functions. This study discovers host-species-specific bacterial symbionts that predate hominid diversification, many of which have undergone accelerated extinctions from human populations.

Malaria-driven adaptation of MHC class I in wild bonobo populations.

The malaria parasite Plasmodium falciparum causes substantial human mortality, primarily in equatorial Africa. Enriched in affected African populations, the B*53 variant of HLA-B, a cell surface protein that presents peptide antigens to cytotoxic lymphocytes, confers protection against severe malaria. Gorilla, chimpanzee, and bonobo are humans' closest living relatives. These African apes have HLA-B orthologs and are infected by parasites in the same subgenus (Laverania) as P. falciparum, but the consequences of these infections are unclear. Laverania parasites infect bonobos (Pan paniscus) at only one (TL2) of many sites sampled across their range. TL2 spans the Lomami River and has genetically divergent subpopulations of bonobos on each side. Papa-B, the bonobo ortholog of HLA-B, includes variants having a B*53-like (B07) peptide-binding supertype profile. Here we show that B07 Papa-B occur at high frequency in TL2 bonobos and that malaria appears to have independently selected for different B07 alleles in the two subpopulations.

A low-cost genomics workflow enables isolate screening and strain-level analyses within microbiomes.

Earth's environments harbor complex consortia of microbes that affect processes ranging from host health to biogeochemical cycles. Understanding their evolution and function is limited by an inability to isolate genomes in a high-throughput manner. Here, we present a workflow for bacterial whole-genome sequencing using open-source labware and the OpenTrons robotics platform, reducing costs to approximately $10 per genome. We assess genomic diversity within 45 gut bacterial species from wild-living chimpanzees and bonobos. We quantify intraspecific genomic diversity and reveal divergence of homologous plasmids between hosts. This enables population genetic analyses of bacterial strains not currently possible with metagenomic data alone.

Determining priority for joint replacement: comparing the views of orthopaedic surgeons and other professionals.

OBJECTIVE: To assess which patient characteristics influence the assessments of urgency for surgery by orthopaedic surgeons and non-orthopaedic professionals. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study of 80 patients requiring elective hip or knee replacement attending a public hospital orthopaedic outpatient clinic or orthopaedic surgeon's private rooms. Patients were interviewed after being placed on the surgery waiting list. The interview asked about the severity of their joint disease and its effects on physical capability, psychological distress and social circumstances. Patient interviews were summarised and presented to assessors who ranked groups of eight patients in order of their perceived urgency for surgery. Eleven orthopaedic surgeon assessors completed 360 patient ratings and nine non-orthopaedic assessors from various professions, including physiotherapy, social work, research, management and engineering, completed 720 patient ratings. MAIN OUTCOME MEASURES: Visual analogue scale rating of patient urgency for surgery; patient rankings for surgery; scores for individual domain contributions to urgency rating. RESULTS: A broad spread of perceived urgency was evident among the patients. For each group of eight patients, there was moderate agreement on overall urgency rankings between the two groups of assessors. Linear regression demonstrated that pain was the dominant determinant of urgency score for both assessor groups. Orthopaedic surgeons also took into account limitations to mobility and concurrent medical illness but gave less priority to psychological distress or social circumstances. For the non-orthopaedic assessors, limitations to mobility, social circumstances and psychological distress also contributed to urgency. CONCLUSION: Both orthopaedic surgeons and non-orthopaedic professionals considered pain the most important factor in establishing urgency and priority for joint replacement. Only the non-orthopaedic professionals considered psychosocial factors important when determining priority for surgery. Broader community discussion about prioritisation for elective surgery is needed to facilitate agreement about which patients factors should be considered.

Aberrant expression of cytokeratin 7 in perivenular hepatocytes correlates with a cholestatic chemistry profile in patients with heart failure.

A cholestatic liver chemistry profile (elevations in alkaline phosphatase and bilirubin) is commonly encountered in patients with hepatic venous outflow obstruction due to right heart failure. Liver biopsies from these patients demonstrate varying degrees of sinusoidal dilatation, red blood cell extravasation and sinusoidal congestion. Recently, a bile ductular reaction mimicking biliary tract disease has been identified in ∼ 50% of patients with venous outflow obstruction possibly explaining the cholestatic profile encountered in these patients. In this study, we evaluated the liver biopsies from 22 patients with heart failure. Marked sinusoidal dilatation involving zones 2 and 3 was observed in 15 patients. Similar to a previous study, 7 of 22 patients had histologic evidence of a mild ductular reaction. Cytokeratin 7 immunohistochemistry revealed a mild ductular reaction in an additional two cases. Strikingly, CK7 was aberrantly expressed in perivenular hepatocytes in 20 of 22 cases. Perivenular CK7 immunoreactivity was focal in most cases; however, in five cases it was quite extensive and extended into zone 2. There was no significant association between marked sinusoidal dilatation and extensive perivenular CK7 positivity. Extensive perivenular CK7 positivity was significantly associated with both elevated bilirubin, as well as the presence of fibrosis. However, a ductular reaction was not associated with a cholestatic liver chemistry profile.

Ancient Introgression between Two Ape Malaria Parasite Species.

The Laverania clade comprises the human malaria parasite Plasmodium falciparum as well as at least seven additional parasite species that infect wild African apes. A recent analysis of Laverania genome sequences (Otto TD, et al. 2018. Genomes of all known members of a Plasmodium subgenus reveal paths to virulent human malaria. Nat Microbiol. 3: 687-697) reported three instances of interspecies gene transfer, one of which had previously been described. Generating gene sequences from additional ape parasites and re-examining sequencing reads generated in the Otto et al. study, we identified one of the newly described gene transfers as an assembly artifact of sequences derived from a sample coinfected by two parasite species. The second gene transfer between ancestors of two divergent chimpanzee parasite lineages was confirmed, but involved a much larger number of genes than originally described, many of which encode exported proteins that remodel, or bind to, erythrocytes. Because successful hybridization between Laverania species is very rare, it will be important to determine to what extent these gene transfers have shaped their host interactions.

Is the risk of concomitant invasive esophageal cancer in high-grade dysplasia in Barrett's esophagus overestimated?

BACKGROUND & AIMS: Recent studies have claimed long neoplasia-free survival rates with endoscopic mucosal resection of high-grade dysplasia (HGD) in Barrett's esophagus (BE). However, reports have contended that approximately 40% of patients who have esophagectomy for HGD have occult invasive cancer. The aim of this study was to use explicit criteria to determine the true prevalence of invasive adenocarcinoma in reports of patients who had esophagectomy for HGD in BE. METHODS: Studies reporting rates of esophageal cancer in patients who underwent esophagectomy for HGD in BE were gathered using MEDLINE and PUBMED. We defined invasive esophageal adenocarcinoma (IEAC) as tumor with submucosal invasion or beyond. Intramucosal carcinoma (IMC) was not considered IEAC. RESULTS: Twenty-three articles were selected for analysis. Most investigators reported rates of invasive cancer in the esophagectomy specimen, and the pooled average was 39.9% among the 441 patients who underwent an esophagectomy for HGD. Reported rates varied from 0% to 73%. A total of 267 patients had American Joint Committee on Cancer stage 0 postoperatively, 132 patients had stage I, 23 patients had stage IIa, 10 patients had stage IIb, and 9 patients had stage III. Fourteen studies provided differentiation between intramucosal and submucosal invasion. Among 213 patients, only 12.7% had IEAC, whereas 87.3% had HGD or IMC. The IEAC rate of 11% among patients with visible lesions is greater than the rate of 3% among patients with no visible lesion. CONCLUSIONS: By using strict pathologic definitions of invasive disease, the present study indicates the true prevalence of IEAC in BE and HGD may have been overestimated significantly. Separating IMC from IEAC is clinically relevant because endoscopic techniques potentially may treat IMC.

Allometry and Ecology of the Bilaterian Gut Microbiome.

Classical ecology provides principles for construction and function of biological communities, but to what extent these apply to the animal-associated microbiota is just beginning to be assessed. Here, we investigated the influence of several well-known ecological principles on animal-associated microbiota by characterizing gut microbial specimens from bilaterally symmetrical animals (Bilateria) ranging from flies to whales. A rigorously vetted sample set containing 265 specimens from 64 species was assembled. Bacterial lineages were characterized by 16S rRNA gene sequencing. Previously published samples were also compared, allowing analysis of over 1,098 samples in total. A restricted number of bacterial phyla was found to account for the great majority of gut colonists. Gut microbial composition was associated with host phylogeny and diet. We identified numerous gut bacterial 16S rRNA gene sequences that diverged deeply from previously studied taxa, identifying opportunities to discover new bacterial types. The number of bacterial lineages per gut sample was positively associated with animal mass, paralleling known species-area relationships from island biogeography and implicating body size as a determinant of community stability and niche complexity. Samples from larger animals harbored greater numbers of anaerobic communities, specifying a mechanism for generating more-complex microbial environments. Predictions for species/abundance relationships from models of neutral colonization did not match the data set, pointing to alternative mechanisms such as selection of specific colonists by environmental niche. Taken together, the data suggest that niche complexity increases with gut size and that niche selection forces dominate gut community construction.IMPORTANCE The intestinal microbiome of animals is essential for health, contributing to digestion of foods, proper immune development, inhibition of pathogen colonization, and catabolism of xenobiotic compounds. How these communities assemble and persist is just beginning to be investigated. Here we interrogated a set of gut samples from a wide range of animals to investigate the roles of selection and random processes in microbial community construction. We show that the numbers of bacterial species increased with the weight of host organisms, paralleling findings from studies of island biogeography. Communities in larger organisms tended to be more anaerobic, suggesting one mechanism for niche diversification. Nonselective processes enable specific predictions for community structure, but our samples did not match the predictions of the neutral model. Thus, these findings highlight the importance of niche selection in community construction and suggest mechanisms of niche diversification.

The mitochondrial ancestor of bonobos and the origin of their major haplogroups.

We report here where the most recent common ancestor (MRCA) of bonobos (Pan paniscus) ranged and how they dispersed throughout their current habitat. Mitochondrial DNA (mtDNA) molecular dating to analyze the time to MRCA (TMRCA) and the major mtDNA haplogroups of wild bonobos were performed using new estimations of divergence time of bonobos from other Pan species to investigate the dispersal routes of bonobos over the forest area of the Congo River's left bank. The TMRCA of bonobos was estimated to be 0.64 or 0.95 million years ago (Ma). Six major haplogroups had very old origins of 0.38 Ma or older. The reconstruction of the ancestral area revealed the mitochondrial ancestor of the bonobo populations ranged in the eastern area of the current bonobos' habitat. The haplogroups may have been formed from either the riparian forests along the Congo River or the center of the southern Congo Basin. Fragmentation of the forest refugia during the cooler periods may have greatly affected the formation of the genetic structure of bonobo populations.

Wild bonobos host geographically restricted malaria parasites including a putative new Laverania species.

Malaria parasites, though widespread among wild chimpanzees and gorillas, have not been detected in bonobos. Here, we show that wild-living bonobos are endemically Plasmodium infected in the eastern-most part of their range. Testing 1556 faecal samples from 11 field sites, we identify high prevalence Laverania infections in the Tshuapa-Lomami-Lualaba (TL2) area, but not at other locations across the Congo. TL2 bonobos harbour P. gaboni, formerly only found in chimpanzees, as well as a potential new species, Plasmodium lomamiensis sp. nov. Rare co-infections with non-Laverania parasites were also observed. Phylogenetic relationships among Laverania species are consistent with co-divergence with their gorilla, chimpanzee and bonobo hosts, suggesting a timescale for their evolution. The absence of Plasmodium from most field sites could not be explained by parasite seasonality, nor by bonobo population structure, diet or gut microbiota. Thus, the geographic restriction of bonobo Plasmodium reflects still unidentified factors that likely influence parasite transmission.

Rab11a immunohistochemical analysis does not distinguish indefinite, low-, and high-grade dysplasia in Barrett esophagus.

Our aim was to determine whether p53 and Rab11a immunoreactivity enhance diagnostic assessment of esophageal dysplasia. Histologic sections from 68 cases of Barrett esophagus obtained as part of a 12-institution study were stained with antibodies to p53 and Rab11a, randomized, and coded. The mucosal surface layer and deeper glands were scored blindly on a semiquantitative scale. The correlations between p53 and Rab11a scoring with the consensus diagnosis of dysplasia were analyzed. The histologic scale was as follows: no dysplasia, indefinite, low-grade dysplasia, high-grade dysplasia, intramucosal carcinoma, and invasive carcinoma. Rab11a staining was most prominent in epithelia negative for dysplasia but with regenerative features. There was an inverse relationship between Rab11a staining and findings of surface dysplasia (P < .02, chi(2)). However, statistical significance largely reflected loss of Rab11a immunoreactivity in intramucosal and invasive carcinoma, which was not a diagnostic dilemma. There was a strong positive correlation of p53 immunoreactivity with an increasing degree of epithelial dysplasia and carcinoma (P < .03, chi(2)). Rab11a immunoreactivity did not enhance the diagnostic assessment of dysplasia in Barrett esophagus. The previously reported positive correlation of p53 immunoreactivity with the presence of dysplasia in Barrett esophagus was confirmed.

Protected areas in tropical Africa: assessing threats and conservation activities.

Numerous protected areas (PAs) have been created in Africa to safeguard wildlife and other natural resources. However, significant threats from anthropogenic activities and decline of wildlife populations persist, while conservation efforts in most PAs are still minimal. We assessed the impact level of the most common threats to wildlife within PAs in tropical Africa and the relationship of conservation activities with threat impact level. We collated data on 98 PAs with tropical forest cover from 15 countries across West, Central and East Africa. For this, we assembled information about local threats as well as conservation activities from published and unpublished literature, and questionnaires sent to long-term field workers. We constructed general linear models to test the significance of specific conservation activities in relation to the threat impact level. Subsistence and commercial hunting were identified as the most common direct threats to wildlife and found to be most prevalent in West and Central Africa. Agriculture and logging represented the most common indirect threats, and were most prevalent in West Africa. We found that the long-term presence of conservation activities (such as law enforcement, research and tourism) was associated with lower threat impact levels. Our results highlight deficiencies in the management effectiveness of several PAs across tropical Africa, and conclude that PA management should invest more into conservation activities with long-term duration.