Sex Differences in Bone Loss – An Evolutionary Perspective on a Clinical Problem

The dramatic increase in the world\u27s population that has occurred over the past 100 years has come largely through reductions in death due to infectious disease. An epidemiologic transition to a preponderance of deaths due to degenerative conditions such as cardiovascular disease and cancer is occurring in the developing countries as well as in the industrialized ones. In the industrialized countries, demographic profiles now reflect the increased life expectancies of both sexes. However, female life expectancies exceed male by six or more years. Further change in mortality patterns will accompany success in the reduction of the number of mortalities attributable to such degenerative conditions as cardiovascular disease and cancer. In the 21st century, conditions associated with senescence will be of increasing concern. Adaptive strategies that enhanced reproductive success throughout most of human evolution may now prove detrimental to human health as average life expectancies reach unprecedented length. In this environment, differences in the survival mechanisms deployed by males as opposed to females will become increasingly important

Metaanalyse zur genetischen Prädisposition bei akuter lymphatischer Leukämie anhand von Polymorphismen

Deutsch: Die akute lymphatische Leukämie stellt die häufigste maligne Erkrankung im Kindesalter dar. Obwohl dieses Krankheitsbild weit verbreitet ist, ist die Pathophysiologie weitgehend unbekannt. Eine multifaktorielle Genese ist wahrscheinlich. Es wurden verschiedene exogene und endogene Faktoren wie Einzelnukleotid-Polymorphismen mit dem Erkrankungsrisiko in Verbindung gebracht. Diese Genveränderungen können je nach Lokalisation die Funktionalität der entsprechenden Gene und Stoffwechselwege einschränken. Genomweite Assoziationsstudien verbanden unter anderem die Gene IKZF1 und CEBPE mit dem Erkrankungsrisiko, da deren Proteine eine wichtige Rolle in der Lympho- und Granulopoese spielen. Außerdem ist bekannt, dass sowohl das Enzym Methylentetrahydrofolatreduktase als auch der Folattransporter 1 eine Rolle in der Erhaltung der Homöostase des Folatstoffwechsels spielen, der unter anderem an der DNA-Synthese beteiligt ist. Deren codierende Gene MTHFR und SLC19A1 wurden erstmals im Jahr 1999 und im Jahr 2001 im Rahmen einer Fall-Kontroll-Studie mit dem Erkrankungsrisiko der akuten lymphatischen Leukämie in Zusammenhang gebracht. Diese vier verschiedenen Gene scheinen eine Rolle in der Pathogenese der akuten lymphatischen Leukämie zu spielen. Es wurden einige Polymorphismen auf den genannten Genabschnitten identifiziert und in zahlreichen Studien untersucht, deren Ergebnisse teilweise widersprüchlich sind. Die Polymorphismen rs4132601 (T > G) und rs11978267 (A > G) auf IKZF1, rs2239633 (G > A) auf CEBPE, rs1801131 (A1298C) und rs1801133 (C677T) auf MTHFR und rs1051266 (G80A) auf SLC19A1 wurden im Rahmen dieser Dissertation untersucht. Zu diesem Zweck wurden die bisher veröffentlichten Arbeiten zu den Genvarianten in der Literaturdatenbank PubMed durchsucht. In einem weiteren Schritt wurde eine Metaanalyse der ausgewählten Publikationen durchgeführt und jeweils die gepoolte Odds Ratio und das 95 %-Konfidenzintervall berechnet. In die Analyse wurden insgesamt 88 Studien eingeschlossen, die 23.844 Patienten mit akuter lymphatischer Leukämie und 74.513 gesunde Kontrollpersonen untersuchten. Die Berechnungen ergaben für die Polymorphismen rs4132601 und rs11978267 im Gen IKZF1 sowohl im rezessiven als auch im dominanten Modell ein statistisch signifikantes Ergebnis. Die Analyse gibt Anlass zu der Annahme, dass Träger des G-Allels in rs4132601 und in rs11978267 ein erhöhtes Erkrankungsrisiko aufweisen. Im Gegensatz dazu weisen die Ergebnisse bezüglich des Polymorphismus rs2239633 im CEBPE-Gen darauf hin, dass Personen, die mindestens ein A-Allel tragen, weniger häufig an akuter lymphatischer Leukämie erkranken. In den jeweiligen Subgruppenanalysen wurden diese Beobachtungen vor allem für die kaukasische Ethnie bestätigt. Bei den Polymorphismen des MTHFR-Gens, rs1801131 und rs1801133, konnte kein signifikanter Zusammenhang nachgewiesen werden. Der dritte Polymorphismus, welcher mit dem Folatstoffwechsel assoziiert ist, rs1051266 auf SLC19A1, zeigt nur im dominanten Modell eine Assoziation des A-Allels mit einem gesteigerten ALL-Risiko.English: Acute lymphoblastic leukemia is the most common malignant disease in children. While a lot of children are suffering from this disease, the pathophysiology stays mainly unknown and a multifactorial etiology seems most likely. Many different intrinsic and extrinsic factors for example single nucleotide polymorphisms were associated with the risk of disease. Depending on their location, genetic variants are capable of limiting the functionality of genes and metabolic pathways. Genome wide association studies identified IKZF1 and CEBPE as risk factors for acute lymphoblastic leukemia, because they play an important role in lympho- and granulopoesis. The enzyme methylenetetrahydrofolate reductase and the corresponding gene, as well as the folatetransporter 1 are involved in the homeostasis of the folate pathway, which is associated with DNA synthesis. The association of acute lymphoblastic leukemia risk and MTHFR was first examined in a case-control study in 1999, while the earliest study with case-control design about SLC19A1 was published in 2001. These four genes may play a role in the pathogenesis of acute lymphoblastic leukemia. Many polymorphisms could be identified on the related gene sequences and were analyzed in several studies whose findings are sometimes inconsistent. In this thesis the single nucleotide polymorphisms rs4132601 (T > G) and rs11978267 (A > G) in IKZF1, rs2239633 (G > A) in CEBPE, rs1801131 (A1298C) and rs1801133 (C677T) in MTHFR and rs1051266 (G80A) in SLC19A1 were examined. For this purpose, the PubMed database was screened for all publications referring to these polymorphisms and acute lymphoblastic leukemia risk. In the next step a meta-analysis of the selected studies was conducted and the odds ratio and 95 % confidence interval were calculated for the single nucleotide polymorphisms. Overall, the analysis included 88 studies containing a total of 23.844 patients with ALL and 74.513 healthy controls. The calculations showed significant association in the dominant and recessive model for the polymorphisms rs4132601 and rs11978267 in IKZF1. Based on this analysis it can be assumed, that there is a higher risk of acute lymphoblastic leukemia in carriers of the G-allele in both loci. In contrast to these results the analysis of the polymorphism rs2239633 in CEBPE revealed a protective effect of the A-allele in acute lymphoblastic leukemia. The subgroup analysis pointed out, that these findings are especially true for Caucasians. The single nucleotide polymorphisms of the MTHFR-Gene rs1801131 and rs1801133 showed no statistically significant results. The third polymorphism, which was studied in connection with the folate pathway was rs1051266 in SLC19A1. In the dominant calculation model the A-allele was associated with increased risk of acute lymphoblastic leukemia

Place Appropriation Method: Byzantine Monuments of Plaka

157 σ.Η παρούσα διπλωματική εργασία επεξεργάζεται τη μεθοδολογία οικειοποίησης του χώρου με στόχο την ανάδειξη της βυζαντινής πολιτιστικής κληρονομιάς της Πλάκας στην Αθήνα και την ευαισθητοποίηση του κοινού υπέρ αυτής. Η μελέτη επικεντρώνεται στις Βυζαντινές Εκκλησίες του 10ου -12ου αιώνα μ.Χ. Οι Βυζαντινές Εκκλησίες προβάλουν την ελληνική παράδοση και την ιστορική συνέχεια της περιοχής. Σκοπός της μεθοδολογίας είναι ο προσδιορισμός της καλύτερης διαδρομής πρόσβασης και επίσκεψης τους, η οποία θα διέπεται από τα αντιληπτικά κριτήρια των κατοίκων και των επισκεπτών. Έτσι σ’ αυτά τα πλαίσια προγραμματίστηκε μια μεθοδολογία διαφόρων ερευνών. Οι έρευνες που έλαβαν χώρα ήταν η περιγραφική (περιγραφή των χαρακτηριστικών στοιχείων της περιοχής), η αντιληπτική (εντοπισμός της αίσθησης που προκαλείται στο κοινό από την περιοχή), η γραφική (απεικόνιση των στοιχείων της περιοχής), η φωτογραφική (λήψη φωτογραφιών). Ακολούθησε η ανάλυση των στοιχείων της περιοχής που διακρίνονται μέσα από χάρτες, αξιοποιώντας τα εργαλεία της χαρτογραφίας, αλλά και η σύνταξη και διάθεση ενός ερωτηματολογίου στους κατοίκους και χρήστες της συνοικίας της Πλάκας. Έτσι αφού συγκεντρώθηκαν και αξιολογήθηκαν όλες οι πληροφορίες, κατασκευάστηκαν χάρτες με τις επιμέρους διαδρομές που έγιναν για την κάλυψη του συνόλου της περιοχής. Στόχος της όλης μελέτης είναι να ευαισθητοποιηθεί το κοινό υπέρ της Βυζαντινής πολιτιστικής κληρονομιάς ή ακόμη και να μάθει για την ύπαρξη κάποιων μνημείων που δεν γνωρίζει. Επίσης οι παραγόμενοι χάρτες μπορούν να χρησιμοποιηθούν από τους πολίτες για την αναζήτηση πληροφοριών, ενώ σε καθημερινό πρακτικό επίπεδο οι χάρτες πρόκειται να αναρτηθούν σε χαρακτηριστικά σημεία (στάσεις) κατά μήκος της προτεινόμενης βέλτιστης διαδρομής.The issue of the present dissertation elaborates a method for the advancement and appreciation of the Byzantine cultural heritage of Plaka which is a particular place and it is entitled «Place Appropriation Method». The work is focused on the Byzantine Churches of 10th -12th century. The Byzantine Churches is part of Greek culture and they testify the historical continuity of region. The purpose of the method is the determination of a better walking access to the visitors and the residents, which will be evaluated by their perception. The last fifty years the bibliography provides various methods and theories. They provide different tools for the evaluation of a place (description of the characteristic elements of a place, perception and definition of the particular atmosphere that place causes to the public and photographic records (reception of photographs). These were the main issues of the presented method. The analysis of all previous elements of the place of Plaka have been elaborated through maps with the purpose to develop some cartographical tools. Also there was distributed a questionnaire in the residents and users of Plaka to reveal the local perception for these monuments. The synthesis of the collected information guided the proposed walking path through Plaka in order to experience and appreciate the Byzantine churches. The walking experience of a place is the mean for the public to appropriate the Byzantine cultural heritage and for the visitors to become familiar with these monuments and understand the Greek history. The produced maps can be used by the citizens for the search of information, while in daily practical level the maps can be placed in characteristic points (attitudes) at length of the proposed most optimal way.Σταματίνα Θ. Στίν

Nutritional influence on childhood development and genetic control of adolescent growth of Quechuas and Mestizos from the Peruvian Lowlands

The growth in height of 1,202 Quechua and Mestizo children aged 6 to 19 years of the province of Lamas in the Peruvian Eastern Lowlands was studied. As shown by evaluations of ABO, Rh systems, and skin reflectance measurements, the Quechuas are genetically different from the Mestizos. The heights of Quechuas and Mestizos were matched for nutritional status based on measurements of subcutaneous fat and body muscle. The study indicates that: (1) during childhood, Quechuas and Mestizos matched for the same nutritional status attain similar heights; (2) during adolescence (or after the age of 11 years), the Mestizos are significantly taller than the Quechuas of the same nutritional status; 3) during childhood, the relative difference in height between Quechuas and Mestizos matched for the same nutritional status is less than the difference between Quechuas (or Mestizos) of the same genetic composition characterized by good and poor nutritional status. These findings suggest that the influence of environmental factors, such as nutrition, have a greater influence in producing differences in body size during childhood than during adolescence. Conversely, the present findings support the hypothesis that the influence of genetic factors on body size are greater during adolescence than during childhood. However, comparison of adolescent samples of similar genetic composition (whether they be Quechuas or Mestizos), characterized by good and poor nutritional status, reveal large differences in height, suggesting that under conditions of malnutrition, the genetic control of growth is diminished.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37600/1/1330520308_ftp.pd

Relationship between body mass, lean mass, fat mass, and limb bone cross-sectional geometry: Implications for estimating body mass and physique from the skeleton.

OBJECTIVES: Estimating body mass from skeletal dimensions is widely practiced, but methods for estimating its components (lean and fat mass) are poorly developed. The ability to estimate these characteristics would offer new insights into the evolution of body composition and its variation relative to past and present health. This study investigates the potential of long bone cross-sectional properties as predictors of body, lean, and fat mass. MATERIALS AND METHODS: Humerus, femur and tibia midshaft cross-sectional properties were measured by peripheral quantitative computed tomography in sample of young adult women (n = 105) characterized by a range of activity levels. Body composition was estimated from bioimpedance analysis. RESULTS: Lean mass correlated most strongly with both upper and lower limb bone properties (r values up to 0.74), while fat mass showed weak correlations (r ≤ 0.29). Estimation equations generated from tibial midshaft properties indicated that lean mass could be estimated relatively reliably, with some improvement using logged data and including bone length in the models (minimum standard error of estimate = 8.9%). Body mass prediction was less reliable and fat mass only poorly predicted (standard errors of estimate ≥11.9% and >33%, respectively). DISCUSSION: Lean mass can be predicted more reliably than body mass from limb bone cross-sectional properties. The results highlight the potential for studying evolutionary trends in lean mass from skeletal remains, and have implications for understanding the relationship between bone morphology and body mass or composition

A multi‐method assessment of bone maintenance and loss in an Imperial Roman population: Implications for future studies of age‐related bone loss in the past

ObjectivesOne of the hallmarks of contemporary osteoporosis and bone loss is dramatically higher prevalence of loss and fragility in females post‐menopause. In contrast, bioarchaeological studies of bone loss have found a greater diversity of age‐ and sex‐related patterns of bone loss in past populations. We argue that the differing findings may relate to the fact that most studies use only a single methodology to quantify bone loss and do not account for the heterogeneity and complexity of bone maintenance across the skeleton and over the life course.MethodsWe test the hypothesis that bone mass and maintenance in trabecular bone sites versus cortical bone sites will show differing patterns of age‐related bone loss, with cortical bone sites showing sex difference in bone loss that are similar to contemporary Western populations, and trabecular bone loss at earlier ages. We investigated this hypothesis in the Imperial Roman population of Velia using three methods: radiogrammetry of the second metacarpal (N = 71), bone histology of ribs (N = 70), and computerized tomography of trabecular bone architecture (N = 47). All three methods were used to explore sex and age differences in patterns of bone loss.ResultsThe suite of methods utilized reveal differences in the timing of bone loss with age, but all methods found no statistically significant differences in age‐related bone loss.DiscussionWe argue that a multi‐method approach reduces the influence of confounding factors by building a reconstruction of bone turnover over the life cycle that a limited single‐method project cannot provide. The implications of using multiple methods beyond studies of bone loss are also discussed.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138337/1/ajpa23256_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138337/2/ajpa23256.pd

Childhood retardation resulting in reduction of adult body size due to lesser adolescent skeletal delay

The skeletal maturation of 7972 rural children from the six Central American nations, aged one month through 22 years, is evaluated. The results suggest that retardation in skeletal maturation during childhood is significantly greater than during adolescence, while growth in body size shows a progressive delay from infancy through adolescence. In other words, the apparent improvement in skeletal maturation during adolescence is not associated with an equivalent “catch-up” in body size. Similarly, prolongation of the period of growth does not fully compensate for the slow rate of growth. It is postulated that the small stature in Central America is related to the marked childhood retardation and to the fact that during adolescence, the timing of skeletal maturation is less affected than growth in size.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37507/1/1330330306_ftp.pd

Human hips, breasts and buttocks: Is fat deceptive?

In humans, reproductive-age females, unlike other ages and classes of individuals, deposit fat preferentially on the breasts, hips, and buttocks. This suggests that such fat deposition is a deceptive sexual signal, mimicking other signals of high reproductive value and potential.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26924/1/0000490.pd

Brief communication: Evidence of pathology on the frontal bone from Gongwangling

The hominid fossil from Gongwangling (Lantian) is well known and described (Woo, [1965] Scientia Sinca 14:1032–1036; Woo [1966] Curr. Anthropol. 7:83–86; Wu and Dong [1985] in R Wu and JW Olsen (eds.): Palaeoanthropology and Paleolithic Archaeology in the People's Republic of China [New York: Academic Press, pp. 79–89]; Wu and Poirier [1995] Human Evolution in China: A Metric Description of the Fossils and a Review of the Sites [Oxford: Oxford University Press]). However, evidence of pathology on the frontal bone has been previously unreported. Two lesions occur on the right supraorbital region that can be distinguished from marks of erosion prevalent on this specimen. These are discrete and irregularly shaped, with evidence of secondary bone formation surrounding them. The cause of the condition is unclear. Possibilities include trauma or abscess from an unspecified infection. Am J Phys Anthropol 102:565–568, 1997. © 1997 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37681/1/10_ftp.pd

Seasonality, resource stress, and food sharing in so-called "egalitarian" foraging societies

Most discussions of food sharing among so-called "egalitarian" hunters and gatherers implicitly assume that, because all adult members of a group participate in the network of sharing, all must therefore be receiving portions of more or less equivalent nutritional worth. This assumption is questioned and five basic points are raised: (1) because fat is not uniformly distributed over the carcass of an animal and because it is depleted sequentially when an animal is stressed, certain individuals may receive nutritionally inferior portions of meat, with potentially serious health consequences for the recipients during seasonal or interannual periods when other food resources are in short supply; (2) even when sharing is quantitatively and nutritionally equitable, food taboos may block certain individuals from access to meat and/or fat, particularly children, women at critical stages in their reproductive life, and the elderly (however, in the case of pregnant women, such food taboos and seemingly inequitable sharing practices may have positive as well as negative consequences for the health and survivorship of the fetus or newborn infant by keeping maternal protein consumption below about 20% of total calories and by reducing the mother's risk of exposure to potentially teratogenic substances that may accumulate in animal tissues); (3) skilled hunters may acquire nutritionally more valuable parts than do other males by "snacking" at kill sites and through differential sharing; (4) food-sharing practices and food taboos vary widely among foragers, and this diversity may contribute to observed differences among groups in fertility and infant mortality patterns; and (5) the focus of anthropologists on the sharing of food, especially meat, as opposed to the sharing of a broad spectrum of social, political, economic, and sexual rights and privileges, is an overly narrow and potentially misleading perspective. In closing, the paper briefly discusses the utility of the term "egalitarian," concluding that the concept, by conflating ideology with actual behavior, may obscure rather than enhance our understanding of the origins and adaptations of foraging societies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28530/1/0000327.pd