Hybridization in human evolution: Insights from other organisms.

During the late Pleistocene, isolated lineages of hominins exchanged genes thus influencing genomic variation in humans in both the past and present. However, the dynamics of this genetic exchange and associated phenotypic consequences through time remain poorly understood. Gene exchange across divergent lineages can result in myriad outcomes arising from these dynamics and the environmental conditions under which it occurs. Here we draw from our collective research across various organisms, illustrating some of the ways in which gene exchange can structure genomic/phenotypic diversity within/among species. We present a range of examples relevant to questions about the evolution of hominins. These examples are not meant to be exhaustive, but rather illustrative of the diverse evolutionary causes/consequences of hybridization, highlighting potential drivers of human evolution in the context of hybridization including: influences on adaptive evolution, climate change, developmental systems, sex-differences in behavior, Haldane's rule and the large X-effect, and transgressive phenotypic variation.

Cranial measures and ancient DNA both show greater similarity of Neandertals to recent modern Eurasians than to recent modern sub-Saharan Africans.

OBJECTIVES: Ancient DNA analysis has shown that present-day humans of Eurasian ancestry are more similar to Neandertals than are present-day humans of sub-Saharan African ancestry, reflecting interbreeding after modern humans first left Africa. We use craniometric data to test the hypothesis that the crania of recent modern humans show the same pattern. MATERIALS AND METHODS: We computed Mahalanobis squared distances between a published Neandertal centroid based on 37 craniometric traits and each of 2,413 recent modern humans from the Howells global data set (N = 373 sub-Saharan Africans, N = 2,040 individuals of Eurasian descent). RESULTS: The average distance to the Neandertal centroid is significantly lower for Eurasian crania than for sub-Saharan African crania as expected from the findings of ancient DNA (p < 0.001). This result holds when examining distances for separate geographic regions of humans of Eurasian descent (Europeans, Asians, Australasians, Native Americans, and Pacific Islanders). Most of these results are also seen when examining distances partitioning size and shape variation. DISCUSSION: Our results show that the genetic difference in Neandertal ancestry seen in the DNA of present-day sub-Saharan Africans and Eurasians is also found in patterns of recent modern human craniometric variation.

Endoscopic multiple biopsy and rapid diagnosis by in situ fixation and histopathologic processing.

BACKGROUND AND AIMS: Endoscopic forceps biopsy and fixation are laborious and prolong the procedure and anesthesia. Multiple biopsy overcomes these shortcomings with a single endoscope pass that cuts, like a needle biopsy, up to 25 biopsy samples of uniform size and depth during endoscope withdrawal. Biopsy specimens are collected in acquisition order and stored in a perforated plastic storage chamber within the perforated metal tip. The tip is cut off, immersed in fixative, and sent to pathology. A formatted log identifies each biopsy specimen by site and position. In pathology, the plastic storage cylinder, designed for processing and microtomy with biopsy specimens in situ, supports rapid diagnosis by frozen section and microwave or routine paraffin processing. METHODS: After a 10-patient Institutional Review Board safety study and US Food and Drug Administration registration, biopsies were performed in 57 patients during colonoscopy, upper GI endoscopy, and ERCP. A blinded retrospective study compared colon surveillance biopsies in 15 patients who underwent multiple biopsy with 15 patients who underwent forceps biopsies performed by anonymous physicians on the same day. Patient information was removed from slides, and forceps biopsies were oriented manually for blinding. RESULTS: Multiple biopsy specimens fixed and processed in situ were not significantly different from batched processed forceps biopsy specimens for depth, orientation, fixation, artifacts, and diagnostic information. Multiple biopsy colonic specimens were significantly (26%) smaller with better epithelial preservation than forceps specimens. Each biopsy saves 61 seconds during withdrawal. CONCLUSIONS: Single-pass multiple biopsy reduces biopsy time with less specimen damage, work, workplace risk, and soiling. Diagnostic quality is equal to forceps biopsy with better epithelial preservation, although 26% smaller. In pathology, in situ processing and microtomy reduce work and workplace risk. Grossing and manual orientation are unnecessary. Rapid diagnosis by frozen section and microwave or paraffin processing are facilitated. Multiple biopsy speeds diagnosis and improves productivity in endoscopic biopsy and histopathologic processing.

Unexpectedly recent dates for human remains from Vogelherd.

The human skeletal remains from the Vogelherd cave in the Swabian Jura of southwestern Germany are at present seen as the best evidence that modern humans produced the artefacts of the early Aurignacian. Radiocarbon measurements from all the key fossils from Vogelherd show that these human remains actually date to the late Neolithic, between 3,900 and 5,000 radiocarbon years before present (bp). Although many questions remain unresolved, these results weaken the arguments for the Danube Corridor hypothesis--that there was an early migration of modern humans into the Upper Danube drainage--and strengthen the view that Neanderthals may have contributed significantly to the development of Upper Palaeolithic cultural traits independent of the arrival of modern humans.

Cardiac epithelioid hemangioendothelioma with 8-year follow-up.

An incidentally discovered right atrial mass excised from the heart of a 51-year-old woman was found on pathological examination to be an epithelioid hemangioendothelioma. No further therapy was undertaken, and the patient has remained free of recurrence for 8 years. To our knowledge, this is the first report on the behavior of this distinctive vascular neoplasm occurring as an isolated cardiac tumor.

Vindija cave and the modern human peopling of Europe.

Vindija cave in Croatia has yielded the youngest securely dated Neandertal skeletal remains in Central/Eastern Europe. In addition, these remains have been found in association with archaeological material exhibiting Upper Paleolithic elements. Due to its geographic location and date, the Vindija remains are particularly crucial for the understanding of initial modern human peopling of Europe and the nature of the Neandertal demise. The significance of archaeological and paleontological finds and hominin fossils from this site is discussed in the light of new finds at Vindija and recent developments in the fields of paleoanthropology and prehistoric archaeology. Furthermore, the impact of revised chronology for several crucial specimens and sites throughout Europe, including Vindija, is discussed.

On some aspects of Neandertal zygomatic morphology.

Neandertals are characterized by a series of well-documented facial characteristics, including midfacial prognathism, large nasal and orbital areas, and a marked supraorbital torus. We provide a comparative morphometric study of another part of this facial complex, the frontal process of the zygomatic. We find that European Neandertals have a distinctly columnar form of the frontal process not found in recent modern humans and most Pleistocene modern humans. Some purportedly modern specimens and specimens pre-dating Neandertals exhibit the same pattern as European Neandertals, while others exhibit the modern human pattern. The columnar form is likely a retention of the ancestral state in Neandertals and the other late Pleistocene specimens that exhibit it, but variation in the pattern seen in early modern humans reveals possible insights into late Pleistocene human evolution.

Global effect of PEG-IFN-alpha and ribavirin on gene expression in PBMC in vitro.

Using oligonucleotide microarrays, we have examined the expression of 22,000 genes in peripheral blood cells treated with pegylated interferon-alpha2b (PEG-IFN-alpha) and ribavirin. Treatment with ribavirin had very little effect on gene expression, whereas treatment with PEG-IFN-alpha had a dramatic effect, modulating the expression of approximately 1000 genes (at p < 0.001). In addition to genes previously reported to be induced by type I or type II IFNs, many novel genes were found to be upregulated, including transcription factors, such as ATF3, ATF4, properdin, a key regulator of the complement pathway, a homeobox gene (HESX1), and an RNA editing enzyme (apobec3). Chemokines CXCL10 and CXCL11 were upregulated, whereas CXCL5 was downregulated. Cytokines interleukin-15 (IL-15) and IL-18 were also significantly induced, whereas IL-1alpha and IL-1beta were downregulated. Most other interleukins were not affected. The results of the microarrays were confirmed by kinetic real-time PCR. These data indicate that IFN treatment causes upregulation of genes associated with the stress response, apoptosis, and signaling, and an equal number of genes are downregulated, including those associated with protein synthesis, specific cytokines and chemokines and other biosynthetic functions.

A review of research on chaplains and community-based clergy in the Journal of the American Medical Association, Lancet, and the New England Journal of Medicine: 1998-2000.

Based on the content analysis of quantitative research appearing in three medical journals, the authors conclude that, despite the shared ideal of providing spiritual care to patients on the part of physicians and chaplains, there is little attention given in these journals demonstrating and promoting this shared perspective. Suggestions for future research that would focus on this common medicine/religion interface and concern are noted.

A counting strategy for estimating plasma cell number in CD138-stained bone marrow core biopsy sections.

Plasma cells are readily identified microscopically after immunostaining for the CD138 antigen, and CD138-stained bone marrow core biopsy sections have proved superior to Giemsa-stained aspirate smears and hematoxylineosin (H&E) sections for determining plasma cell percentages in marrow. The CD138-stained plasma cell percentage is generally obtained by visual estimation, after viewing the entire section. We propose an alternative method, in which the microscopist initially views the immunostained section under low- and medium-power magnification, then selects a single high-power field in which the relative concentration of plasma cells appears most representative of the section as a whole, and performs a manual differential count of plasma cells in that field. On 44 CD138-stained core biopsy specimens from patients with plasma cell myeloma, selected area counting provided plasma cell percentage values that were more closely correlated with total section plasma cell area, determined by computerized image cytometry, than were visual estimates. This simple method requires only slightly more time than visual appraisal, does not require extensive training or experience, and appears to provide a more accurate estimate of the plasma cell population within the entire specimen.

Potential role of nuclear appearance in pathologic recognition and delimitation of sessile serrated polyps of the colon: a karyometric study.

OBJECTIVE: To estimate the extent to which surgical pathologists can rely on abnormal nuclear appearance to recognize sessile serrated adenoma (SSP) and to define its extent. STUDY DESIGN: Digitized images of nuclei of superficial crypt cells from SSPs, banal hyperplastic polyps (BHPs), tubular adenomas (TAs) and normal colonic mucosa (N) in surgical pathology specimens were analyzed for size, shape, area, optical density (summed and average) and 22 Markovian texture characteristics. RESULTS: Statistical classification functions correctly distinguished TA from N nuclear image profiles in 93.3% of cases, SSP from N in 70.0% and BHP from N in 74.1%. SSP nuclear feature vectors were less effectively separated from N than BHP and TA on discriminant analysis of the combined data set, and correct classification was achieved in 79.6% of TAs, 53.5% of SSPs and N and 64.2% of BHPs. CONCLUSION: Karyometry distinguished stained nuclei of TAs, but had limited ability to separate nuclei of SSP from those of N and BHP. This suggests that the pathologist attempting to diagnose or delimit the margins of an SSP will find nuclear appearances less helpful than when examining a TA.

Out of the veil of death rode the one million! Neandertals and their genes.

Two recent papers report extensive nuclear DNA sequence from a 38,000-year-old Neandertal fossil, comparing it to modern humans and estimating when it diverged from, and whether it contributed to, our gene pool. Based on 65,250 and over a million base-pairs of sequence across the genome, respectively, the groups arrived at slightly different interpretations. The data are an exciting and interesting new contribution, but are not surprising, and a sense of history and question helps put them in perspective.

Ontogenetic study of the supraorbital region in modern humans: a longitudinal test of the spatial model.

The structural significance of the hominid supraorbital torus and its morphological variation have always been a controversial topic in physical anthropology. Understanding the function of browridge variation in living and fossil human populations is relevant to questions of human evolution. This study utilizes radiograph images to evaluate the spatial model in modern humans during ontogeny. This structural model attributes variation in the supraorbital region to the positional relationship between the neurocranium and the orbits. The relationship between measurements of the antero-posterior supraorbital length and the factors specified in the spatial model were assessed by correlation and partial correlation analyses. Growth rates were also examined to study ontogenetic trajectories and infer aspects of developmental relationships between critical variables. Results agree with previous research supporting the existence of spatial influences between the neural and orbital-upper facial regions on browridge length during ontogeny.

Revised direct radiocarbon dating of the Vindija G1 Upper Paleolithic Neandertals.

The 1998/1999 direct dating of two Neandertal specimens from level G(1) of Vindija Cave in Croatia to approximately 28,000 and approximately 29,000 radiocarbon ((14)C) years ago has led to interpretations concerning the late survival of Neandertals in south-central Europe, patterns of interaction between Neandertals and in-dispersing early modern humans in Europe, and complex biocultural scenarios for the earlier phases of the Upper Paleolithic. Given improvements, particularly in sample pretreatment techniques for bone radiocarbon samples, especially ultrafiltration of collagen samples, these Vindija G(1) Neandertal fossils are redated to approximately 32,000-33,000 (14)C years ago and possibly earlier. These results and the recent redating of a number of purportedly old modern human skeletal remains in Europe to younger time periods highlight the importance of fine chronological control when studying this biocultural time period and the tenuous nature of monolithic scenarios for the establishment of modern humans and earlier phases of the Upper Paleolithic in Europe.

The ligation of coronary arteries with electrocardiographic study. 1918.

This article is based on a study of sixty-six dogs in which known myocardial lesions had been produced by the ligation of definite branches of the coronary arteries of the heart. While the experiments were made with the primary object of determining the change in the electrocardiograms brought about by these ligations, other results, anatomic and pathologic, are deemed worthy of brief mention.

Hidradenoma papilliferum of nasal skin.

Pathologic examination of an excisional biopsy specimen of a subepidermal nodule from the nasal tip of a 37-year-old black man demonstrated papillae covered by eosinophilic columnar epithelial cells, suggesting cylindric cell papilloma or well-differentiated papillary adenocarcinoma of nasal mucosa. The patient did not submit to further investigation of the sinonasal tract but sought attention 15 months later because of local recurrence of the lesion. A protuberant, 3-cm, cystic nodule of the subcutis over the left nasal ala and tip was excised completely and found to have characteristics of hidradenoma papilliferum, an apocrine gland neoplasm most commonly occurring in the anogenital skin of white women. This case demonstrates how easily an apocrine neoplasm arising near a mucocutaneous junction can be confused with a mucosal tumor, potentially leading to inappropriate treatment.

New discoveries and interpretations of hominid fossils and artifacts from Vindija Cave, Croatia.

Beginning with excavations during the 1970s, Vindija Cave (Croatia) has yielded significant Middle and Upper Paleolithic fossil and archaeological finds. We report on seven recently identified hominid fossils, a newly associated partial hominid cranial vault from level G(3), nine possible bone retouchers, and a revised interpretation of the Mousterian artifact assemblage from the site. This new information reinforces our knowledge of the complex biocultural phenomena revealed in unit G and earlier deposits at Vindija. Six of the new hominid fossils derive from stratigraphic units G and I, while one lacks exact provenience. All specimens preserving diagnostic anatomy are from Neandertals. One of the postcranial remains, a radius fragment which exhibits Neandertal-like anatomy, comes from level G(1)and is congruent with the previously established association of Neandertals with an early Upper Paleolithic industry at the site. The partial cranial vault represents the most complete Neandertal from Vindija. The possible retouchers derive from unit G. Our analysis of these artifacts suggests that both percussion and pressure techniques may have been used by Neandertals in the final stage of tool production (retouching). This paper also presents a revision of the artifact analysis for late Mousterian level G(3). We separated raw materials into two main groups due to the differing ways that the materials fracture and the differing morphology of the debitage. The use of raw material in level G(3)is different from earlier Middle Paleolithic levels at Vindija. This indicates that the G(3)late Neandertals were making choices regarding source material somewhat more like the Upper Paleolithic people at the site. When interpreted within a larger regional framework, the Vindija archaeological and hominid fossil remains demonstrate a complex, mosaic pattern of biocultural change in the Late Pleistocene of south-central Europe.

The Neandertal type site revisited: interdisciplinary investigations of skeletal remains from the Neander Valley, Germany.

The 1856 discovery of the Neandertal type specimen (Neandertal 1) in western Germany marked the beginning of human paleontology and initiated the longest-standing debate in the discipline: the role of Neandertals in human evolutionary history. We report excavations of cave sediments that were removed from the Feldhofer caves in 1856. These deposits have yielded over 60 human skeletal fragments, along with a large series of Paleolithic artifacts and faunal material. Our analysis of this material represents the first interdisciplinary analysis of Neandertal remains incorporating genetic, direct dating, and morphological dimensions simultaneously. Three of these skeletal fragments fit directly on Neandertal 1, whereas several others have distinctively Neandertal features. At least three individuals are represented in the skeletal sample. Radiocarbon dates for Neandertal 1, from which a mtDNA sequence was determined in 1997, and a second individual indicate an age of approximately 40,000 yr for both. mtDNA analysis on the same second individual yields a sequence that clusters with other published Neandertal sequences.