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Concept: Skeleton

202

We have examined the remains of a Pilgrim burial from St Mary Magdalen, Winchester. The individual was a young adult male, aged around 18-25 years at the time of death. Radiocarbon dating showed the remains dated to the late 11th-early 12th centuries, a time when pilgrimages were at their height in Europe. Several lines of evidence in connection with the burial suggested this was an individual of some means and prestige. Although buried within the leprosarium cemetery, the skeleton showed only minimal skeletal evidence for leprosy, which was confined to the bones of the feet and legs. Nonetheless, molecular testing of several skeletal elements, including uninvolved bones all showed robust evidence of DNA from Mycobacterium leprae, consistent with the lepromatous or multibacillary form of the disease. We infer that in life, this individual almost certainly suffered with multiple soft tissue lesions. Genotyping of the M.leprae strain showed this belonged to the 2F lineage, today associated with cases from South-Central and Western Asia. During osteological examination it was noted that the cranium and facial features displayed atypical morphology for northern European populations. Subsequently, geochemical isotopic analyses carried out on tooth enamel indicated that this individual was indeed not local to the Winchester region, although it was not possible to be more specific about their geographic origin.

Concepts: Bone, Mycobacterium, Isotope, Skeleton, Leprosy, Mycobacterium leprae, The Passion of the Christ, Mary Magdalene

172

A finding of high BMD on routine DXA scanning is not infrequent and most commonly reflects degenerative disease. However, BMD increases may also arise secondary to a range of underlying disorders affecting the skeleton. Although low BMD increases fracture risk, the converse may not hold for high BMD, since elevated BMD may occur in conditions where fracture risk is increased, unaffected or reduced. Here we outline a classification for the causes of raised BMD, based on identification of focal or generalized BMD changes, and discuss an approach to guide appropriate investigation by clinicians after careful interpretation of DXA scan findings within the context of the clinical history. We will also review the mild skeletal dysplasia associated with the currently unexplained high bone mass phenotype and discuss recent advances in osteoporosis therapies arising from improved understanding of rare inherited high BMD disorders.

Concepts: Osteoporosis, Bone, Bone density, Density, Skeletal system, Dual energy X-ray absorptiometry, Human skeleton, Skeleton

164

Physical activity is recommended for skeletal health because bones adapt to mechanical loading. The young skeleton shows greatest plasticity to physical activity-related mechanical loads, but bones are most at risk of failure later in life. The discrepancy raises the question of whether the skeletal benefits of physical activity completed when young persist with aging. Here we present a unique case wherein the cortical bone benefit of physical activity completed over five decades earlier could be established within an individual aged in their tenth decade of life. Specifically, we compared bone properties at the midshaft humerus between the throwing and nonthrowing arms of a 94-year-old former Major League Baseball player who ceased throwing 55 years earlier. By performing analyses within-subject, the long-term skeletal benefit of physical activity completed when young could be assessed independent of inherited and systemic traits. Also, as the subject threw left-handed during his throwing career, but was right-hand dominant in all other activities throughout life, any lasting skeletal benefits in favor of the throwing arm could not be attributable to simple arm dominance. Analyses indicated that any cortical bone mass, area and thickness benefits of throwing-related physical activity completed when young were lost with aging, possibly due to accelerated intracortical remodeling. In contrast, the subject’s throwing (nondominant) arm had greater total cross-sectional area and estimated strength (polar moment of inertia) than in his dominant arm, despite muscle indices favoring the latter. These data indicate that physical activity completed when young can have lasting benefits on bone size and strength, independent of the maintenance of bone mass benefits.

Concepts: Bone, Skeletal system, Ageing, Intramembranous ossification, Area, Moment of inertia, Skeleton, Major League Baseball

82

Preceramic human skeletal remains preserved in submerged caves near Tulum in the Mexican state of Quintana Roo, Mexico, reveal conflicting results regarding 14C dating. Here we use U-series techniques for dating a stalagmite overgrowing the pelvis of a human skeleton discovered in the submerged Chan Hol cave. The oldest closed system U/Th age comes from around 21 mm above the pelvis defining the terminus ante quem for the pelvis to 11311±370 y BP. However, the skeleton might be considerable older, probably as old as 13 ky BP as indicated by the speleothem stable isotope data. The Chan Hol individual confirms a late Pleistocene settling of Mesoamerica and represents one of the oldest human osteological remains in America.

Concepts: United States, Mexico, Cave, Human skeleton, Skeleton, Mexico City, Speleothem, Quintana Roo

49

King Philip II was the father of Alexander the Great. He suffered a notorious penetrating wound by a lance through his leg that was nearly fatal and left him lame in 339 B.C.E. (i.e., 3 y before his assassination in 336 B.C.E.). In 1977 and 1978 two male skeletons were excavated in the Royal Tombs II and I of Vergina, Greece, respectively. Tomb I also contained another adult (likely a female) and a newborn skeleton. The current view is that Philip II was buried in Tomb II. However, the male skeleton of Tomb II bears no lesions to his legs that would indicate lameness. We investigated the skeletal material of Tomb I with modern forensic techniques. The male individual in Tomb I displays a conspicuous case of knee ankylosis that is conclusive evidence of lameness. Right through the overgrowth of the knee, there is a hole. There are no obvious signs that are characteristic of infection and osteomyelitis. This evidence indicates that the injury was likely caused by a severe penetrating wound to the knee, which resulted in an active inflammatory process that stopped years before death. Standard anthropological age-estimation techniques based on dry bone, epiphyseal lines, and tooth analysis gave very wide age ranges for the male, centered around 45 y. The female would be around 18-y-old and the infant would be a newborn. It is concluded that King Philip II, his wife Cleopatra, and their newborn child are the occupants of Tomb I.

Concepts: Human skeleton, Skeleton, Alexander the Great, Philip II of Spain, Philip II of Macedon, Olympias, Philip III of Macedon, Alexander IV of Macedon

46

Reduced bone mineral density (BMD) and its clinical sequelae, osteoporosis, occur at a much greater rate the rate in patients with Alzheimer’s disease (AD), often emerging early in the disease before significant cognitive decline is seen. Reduced BMD translates to increased bone fracture risk, decreased quality of life, and increased mortality for AD patients. However, the mechanism responsible for this observation is unclear. We hypothesize that bone loss is an additional component of an AD prodrome, changes that emerge prior to dementia and are mediated by dysfunction of the central serotonergic pathways. We characterized the skeletal phenotype of htau mice that express human forms of the microtubule-associated protein tau that become pathologically hyperphosphorylated in AD. Using radiographic densitometry, we measured BMD in female and male htau mice from 2-6 months of age-time-points prior to the presence of significant tauopathy in the hippocampal/entorhinal regions characteristic of this model. We found a significantly reduced BMD phenotype in htau mice that was most pronounced in males. Using western blotting and immunofluorescence, we showed overall reduced tryptophan hydroxylase (TPH) protein in htau brainstem and a 70% reduction in TPH-positive cells in the dorsal raphe nucleus (DRN)-a pivotal structure in the regulation of the adult skeleton. Elevations of hyperphosphorylated tau (ptau) proteins were also measured in brainstem, and co-labeled immunofluorescence studies showed presence of ptau in TPH-positive cells of the DRN as early as 4 months of age in htau mice. Together, these findings demonstrate that reduced BMD occurs earlier than overt degeneration in a tau-based AD model and that pathological changes in the tau phosphorylation occur in the serotonin-producing neurons of the brainstem raphe in these mice. This illuminates a need to define a mechanistic relationship between bone loss and serotonergic deficits in early AD.

Concepts: Alzheimer's disease, Osteoporosis, Gene, Bone density, Skeletal system, Serotonin, Skeleton, Tau protein

43

It has been posited that the consumption of extra protein (> 0.8 g/kg/d) may be deleterious to bone mineral content. However, there is no direct evidence to show that consuming a high-protein diet results in a demineralization of the skeleton. Thus, the primary endpoint of this randomized controlled trial was to determine if a high-protein diet affected various parameters of whole body and lumbar bone mineral content in exercise-trained women.

Concepts: Protein, Nutrition, Collagen, The Canon of Medicine, Randomized controlled trial, Diet, Skeleton, Evidence law

37

Body mass is a key biological variable, but difficult to assess from fossils. Various techniques exist for estimating body mass from skeletal parameters, but few studies have compared outputs from different methods. Here, we apply several mass estimation methods to an exceptionally complete skeleton of the dinosaur Stegosaurus. Applying a volumetric convex-hulling technique to a digital model of Stegosaurus, we estimate a mass of 1560 kg (95% prediction interval 1082-2256 kg) for this individual. By contrast, bivariate equations based on limb dimensions predict values between 2355 and 3751 kg and require implausible amounts of soft tissue and/or high body densities. When corrected for ontogenetic scaling, however, volumetric and linear equations are brought into close agreement. Our results raise concerns regarding the application of predictive equations to extinct taxa with no living analogues in terms of overall morphology and highlight the sensitivity of bivariate predictive equations to the ontogenetic status of the specimen. We emphasize the significance of rare, complete fossil skeletons in validating widely applied mass estimation equations based on incomplete skeletal material and stress the importance of accurately determining specimen age prior to further analyses.

Concepts: Scientific method, Prediction, Futurology, Estimation, Skeleton, Dinosaur

35

In November and December 2013, unidentified human skeletal remains buried in a mokgwakmyo (a traditional wooden coffin) were unearthed while conducting an archaeological investigation near Gyeongju, which was the capital of the Silla Kingdom (57 BCE- 660 CE) of ancient Korea. The human skeletal remains were preserved in relatively intact condition. In an attempt to obtain biological information on the skeleton, physical anthropological, mitochondrial DNA, stable isotope and craniofacial analyses were carried out. The results indicated that the individual was a female from the Silla period, of 155 ± 5 cm height, who died in her late thirties. The maternal lineage belonged to the haplogroup F1b1a, typical for East Asia, and the diet had been more C3- (wheat, rice and potatoes) than C4-based (maize, millet and other tropical grains). Finally, the face of the individual was reconstructed utilizing the skull (restored from osseous fragments) and three-dimensional computerized modeling system. This study, applying multi-dimensional approaches within an overall bio-anthropological analysis, was the first attempt to collect holistic biological information on human skeletal remains dating to the Silla Kingdom period of ancient Korea.

Concepts: Seoul, Human skeleton, Skeleton, Goguryeo, History of Korea, Balhae, Three Kingdoms of Korea, Silla

35

Seventy-one individuals from the late Neolithic population of the 7000-year-old site of Hódmezővásárhely-Gorzsa were examined for their skeletal palaeopathology. This revealed numerous cases of infections and non-specific stress indicators in juveniles and adults, metabolic diseases in juveniles, and evidence of trauma and mechanical changes in adults. Several cases showed potential signs of tuberculosis, particularly the remains of the individual HGO-53. This is an important finding that has significant implications for our understanding of this community. The aim of the present study was to seek biomolecular evidence to confirm this diagnosis. HGO-53 was a young male with a striking case of hypertrophic pulmonary osteopathy (HPO), revealing rib changes and cavitations in the vertebral bodies. The initial macroscopic diagnosis of HPO secondary to tuberculosis was confirmed by analysis of Mycobacterium tuberculosis complex specific cell wall lipid biomarkers and corroborated by ancient DNA (aDNA) analysis. This case is the earliest known classical case of HPO on an adult human skeleton and is one of the oldest palaeopathological and palaeomicrobiological tuberculosis cases to date.

Concepts: Cell, Metabolism, Skeletal system, Tuberculosis, Mycobacterium, Neolithic, Human skeleton, Skeleton