Light microscopy, particularly the use of polarized light, has such a high value for the differential diagnosis of dry bones that it can no longer be neglected. Alterations caused intra vitam by disease or other living conditions can clearly be differentiated by this technique from changes due to postmortem reactions (e.g., pseudopathology). As a reliable diagnosis is the basis not only of the study of case reports but also of the etiology and epidemiology of diseases in ancient populations, paleopathologists would be well-advised to employ histological analysis for their research, to avoid false diagnoses. The necessary basis for such research is the knowledge of the general histology, histogenesis, and growth as well as pathophysiology of bone. Some new techniques which facilitate the practical use of microscopic analysis, such as the preparation of thin-ground sections from undecalcified bone samples and nonrehydrated mummified soft tissues, are described. Selected examples of mechanisms of pathological bone changes, particularly the determination of vestiges of diseases in macerated bones by microscopy, are presented. Emphasis is placed on the differential diagnoses of proliferative reactions (e.g., periosteal processes of long bones and the skull). In this context, the importance of meningeal reactions on the endocranial lamina of the skull for morbidity and mortality in ancient populations is demonstrated. Furthermore, porotic hyperostosis of the skull vault and the orbital roof, i.e., the cribra cranii externa and cribra orbitalia, is discussed. Selected examples of the etiology and epidemiology of ancient diseases are presented (e.g., anemia, scurvy, rickets, and meningeal diseases), and ideas on living conditions and their implications for the origin and the spread of disease are given to establish a better understanding of deficiency and infectious diseases in the past.

From AD 1347 to AD 1353, the Black Death killed tens of millions of people in Europe, leaving misery and devastation in its wake, with successive epidemics ravaging the continent until the 18th century. The etiology of this disease has remained highly controversial, ranging from claims based on genetics and the historical descriptions of symptoms that it was caused by Yersinia pestis to conclusions that it must have been caused by other pathogens. It has also been disputed whether plague had the same etiology in northern and southern Europe. Here we identified DNA and protein signatures specific for Y. pestis in human skeletons from mass graves in northern, central and southern Europe that were associated archaeologically with the Black Death and subsequent resurgences. We confirm that Y. pestis caused the Black Death and later epidemics on the entire European continent over the course of four centuries. Furthermore, on the basis of 17 single nucleotide polymorphisms plus the absence of a deletion in glpD gene, our aDNA results identified two previously unknown but related clades of Y. pestis associated with distinct medieval mass graves. These findings suggest that plague was imported to Europe on two or more occasions, each following a distinct route. These two clades are ancestral to modern isolates of Y. pestis biovars Orientalis and Medievalis. Our results clarify the etiology of the Black Death and provide a paradigm for a detailed historical reconstruction of the infection routes followed by this disease.

Light microscopy, particularly the use of polarized light, has such a high value for the differential diagnosis of dry bones that it can no longer be neglected. Alterations caused intra vitam by disease or other living conditions can clearly be differentiated by this technique from changes due to postmortem reactions (e.g., pseudopathology). As a reliable diagnosis is the basis not only of the study of case reports but also of the etiology and epidemiology of diseases in ancient populations, paleopathologists would be well-advised to employ histological analysis for their research, to avoid false diagnoses. The necessary basis for such research is the knowledge of the general histology, histogenesis, and growth as well as pathophysiology of bone. Some new techniques which facilitate the practical use of microscopic analysis, such as the preparation of thin-ground sections from undecalcified bone samples and nonrehydrated mummified soft tissues, are described. Selected examples of mechanisms of pathological bone changes, particularly the determination of vestiges of diseases in macerated bones by microscopy, are presented. Emphasis is placed on the differential diagnoses of proliferative reactions (e.g., periosteal processes of long bones and the skull). In this context, the importance of meningeal reactions on the endocranial lamina of the skull for morbidity and mortality in ancient populations is demonstrated. Furthermore, porotic hyperostosis of the skull vault and the orbital roof, i.e., the cribra cranii externa and cribra orbitalia, is discussed. Selected examples of the etiology and epidemiology of ancient diseases are presented (e.g., anemia, scurvy, rickets, and meningeal diseases), and ideas on living conditions and their implications for the origin and the spread of disease are given to establish a better understanding of deficiency and infectious diseases in the past.

I. Introduction 4495 A. Synthesis of a GlycoundecapeptidesMajor Problems and Solutions 4496 1. Synthesis of the Sialyl−Tn Building Block 4496 2. Solid-Phase Synthesis of Undecaglycopeptide 1 4498 II. O-Glycopeptides Carrying Mono-and Disaccharides 4499 A. O-Glycopeptides Carrying RGalNAc 4499 B. Glycopeptides Carrying the T Antigen (βGal-1,3-RGalNAc) 4500 C. O-Glycopeptides Carrying βGlcNAc 4503 D. O-Fucosylated Glycopeptides 4505 E. O-Glycopeptides Carrying the Sialyl−Tn Antigen (RNeuNAc-2,6-RGalNAc) 4505 F. Collagen Type II Derived Glycopeptides Carrying β-Gal and RGlc-1,2-βGal Side Chains

Cribra orbitalia is a porotic or sieve-like lesion in the bony orbital roof. Its cause has been the object of research and discussion since the end of the 19th century. Since about 1960, most scientists have started to agree on the hypothesis that the lesion is a result of hypertrophy of the red bone marrow, and therefore is proof of anemia. However, recent investigations showed that in some cases, the histologic bone structure does not support the diagnosis of anemia. The status of cribra orbitalia as an indicator then becomes uncertain. We carried out a histologic examination of thin-ground sections in polarized light to clarify the possible sources of orbital roof lesions in a Nubian population from Missiminia, northern Sudan (n = 333). In at least 56.5% of cribra orbitalia cases, there were no histologic features indicating changes due to anemia. Signs of other pathological conditions, such as inflammation or osteoporosis, as well as pseudopathological cases, were found.