A parasitic coevolution since the Miocene revealed by phase-contrast synchrotron X-ray microtomography and the study of natural history collections.

The discovery of a new fossil species of the Caribbeo-Mexican genus Proptomaphaginus (Coleoptera, Leiodidae, Cholevinae) from Dominican amber, associated with a new fossil parasitic fungus in the genus Columnomyces (Ascomycota, Laboulbeniales), triggered an investigation of extant species of Proptomaphaginus and revealed the long-enduring parasitic association between these two genera. This effort resulted in the description of the fossil species †Proptomaphaginus alleni sp. nov., and one fossil and two extant species of Columnomyces, selectively associated with species of Proptomaphaginus: †Columnomyces electri sp. nov. associated with the fossil †Proptomaphaginus alleni in Dominican amber, Columnomyces hispaniolensis sp. nov. with the extant Proptomaphaginus hispaniolensis (endemic of Hispaniola), and Columnomyces peckii sp. nov. with the extant Proptomaphaginus puertoricensis (endemic of Puerto Rico). Based on biogeography, our current understanding is that the Caribbean species of Proptomaphaginus and their parasitic species of Columnomyces have coevolved since the Miocene. This is the first occurrence of such a coevolution between a genus of parasitic fungus and a genus of Coleoptera. The phylogenetic relations among Proptomaphaginus species are also addressed based on a parsimony analysis. Fossil specimens were observed by propagation phase-contrast synchrotron X-ray microtomography (PPC-SRμCT) and extant specimens were obtained through the study of preserved dried, pinned insects, attesting for the importance of (i) technological advancement and (ii) natural history collections in the study of microparasitic relationships

Australopithecus afarensis endocasts suggest ape-like brain organization and prolonged brain growth

Human brains are three times larger, are organized differently, and mature for a longer period of time than those of our closest living relatives, the chimpanzees. Together, these characteristics are important for human cognition and social behavior, but their evolutionary origins remain unclear. To study brain growth and organization in the hominin species Australopithecus afarensis more than 3 million years ago, we scanned eight fossil crania using conventional and synchrotron computed tomography. We inferred key features of brain organization from endocranial imprints and explored the pattern of brain growth by combining new endocranial volume estimates with narrow age at death estimates for two infants. Contrary to previous claims, sulcal imprints reveal an ape-like brain organization and no features derived toward humans. A comparison of infant to adult endocranial volumes indicates protracted brain growth in A. afarensis, likely critical for the evolution of a long period of childhood learning in hominins

A mathematical model for mechanotransduction at the early steps of suture formation

Growth and patterning of craniofacial sutures are subjected to the effects of mechanical stress. Mechanotransduction processes occurring at the margins of the sutures are not precisely understood. Here, we propose a simple theoretical model based on the orientation of collagen fibres within the suture in response to local stress. We demonstrate that fibre alignment generates an instability leading to the emergence of interdigitations. We confirm the appearance of this instability both analytically and numerically. To support our model, we use histology and synchrotron x-ray microtomography and reveal the fine structure of fibres within the sutural mesenchyme and their insertion into the bone. Furthermore, using a mouse model with impaired mechanotransduction, we show that the architecture of sutures is disturbed when forces are not interpreted properly. Finally, by studying the structure of sutures in the mouse, the rat, an actinopterygian (\emph{Polypterus bichir}) and a placoderm (\emph{Compagopiscis croucheri}), we show that bone deposition patterns during dermal bone growth are conserved within jawed vertebrates. In total, these results support the role of mechanical constraints in the growth and patterning of craniofacial sutures, a process that was probably effective at the emergence of gnathostomes, and provide new directions for the understanding of normal and pathological suture fusion

Epstein-Barr virus nuclear antigen 3A protein regulates CDKN2B transcription via interaction with MIZ-1

The Epstein-Barr virus (EBV) nuclear antigen 3 family of protein is critical for the EBV-induced primary B-cell growth transformation process. Using a yeast two-hybrid screen we identified 22 novel cellular partners of the EBNA3s. Most importantly, among the newly identified partners, five are known to play direct and important roles in transcriptional regulation. Of these, the Myc-interacting zinc finger protein-1 (MIZ-1) is a transcription factor initially characterized as a binding partner of MYC. MIZ-1 activates the transcription of a number of target genes including the cell cycle inhibitor CDKN2B. Focusing on the EBNA3A/MIZ-1 interaction we demonstrate that binding occurs in EBV-infected cells expressing both proteins at endogenous physiological levels and that in the presence of EBNA3A, a significant fraction of MIZ-1 translocates from the cytoplasm to the nucleus. Moreover, we show that a trimeric complex composed of a MIZ-1 recognition DNA element, MIZ-1 and EBNA3A can be formed, and that interaction of MIZ-1 with nucleophosmin (NPM), one of its coactivator, is prevented by EBNA3A. Finally, we show that, in the presence of EBNA3A, expression of the MIZ-1 target gene, CDKN2B, is downregulated and repressive H3K27 marks are established on its promoter region suggesting that EBNA3A directly counteracts the growth inhibitory action of MIZ-1

Developmental simulation of the adult cranial morphology of australopithecus sediba.

The type specimen of Australopithecus sediba (MH1) is a late juvenile, prompting some commentators to suggest that had it lived to adulthood its morphology would have changed sufficiently so as to render hypotheses regarding its phylogenetic relations suspect. Considering the potentially critical position of this species with regard to the origins of the genus Homo, a deeper understanding of this change is especially vital. As an empirical response to this critique, a developmental simulation of the MH1 cranium was carried out using geometric morphometric techniques to extrapolate adult morphology using extant male and female chimpanzees, gorillas and humans by modelling remaining development. Multivariate comparisons of the simulated adult A. sediba crania with other early hominin taxa indicate that subsequent cranial development primarily reflects development of secondary sexual characteristics and would not likely be substantial enough to alter suggested morphological affinities of A. sediba. This study also illustrates the importance of separating developmental vectors by sex when estimating ontogenetic change. Results of the ontogenetic projections concur with those from mandible morphology, and jointly affirm the taxonomic validity of A. sediba.Andrew W. Mellon Foundation and National Geographic Society.NCS201

Osteogenic tumour in Australopithecus sediba: Earliest hominin evidence for neoplastic disease

We describe the earliest evidence for neoplastic disease in the hominin lineage. This is reported from the type specimen of the extinct hominin Australopithecus sediba from Malapa, South Africa, dated to 1.98 million years ago. The affected individual was male and developmentally equivalent to a human child of 12 to 13 years of age. A penetrating lytic lesion affected the sixth thoracic vertebra. The lesion was macroscopically evaluated and internally imaged through phase-contrast X-ray synchrotron microtomography. A comprehensive differential diagnosis was undertaken based on gross- and micro-morphology of the lesion, leading to a probable diagnosis of osteoid osteoma. These neoplasms are solitary, benign, osteoid and bone-forming tumours, formed from well-vascularised connective tissue within which there is active production of osteoid and woven bone. Tumours of any kind are rare in archaeological populations, and are all but unknown in the hominin record, highlighting the importance of this discovery. The presence of this disease at Malapa predates the earliest evidence of malignant neoplasia in the hominin fossil record by perhaps 200 000 years.NCS201

Contribution of chronic diseases to the mild and severe disability burden in Belgium

Background: Population aging accompanied by an increased longevity with disability has raised international concern, especially due to its costs to the health care systems. Chronic diseases are the main causes of physical disability and their simultaneous occurrence in the population can impact the disablement process, resulting in different severity levels. In this study, the contribution of chronic diseases to both mild and severe disability burden in Belgium was investigated. Methods: Data on 21 chronic diseases and disability from 35,799 individuals aged 15years or older who participated in the 1997, 2001, 2004, or 2008 Belgian Health Interview Surveys were analysed. Mild and severe disability were defined based on questions related to six activities of daily living and/or mobility limitations. To attribute disability by severity level to selected chronic diseases, multiple additive hazard models were fitted to each disability outcome, separately for men and women. Results: A stable prevalence of mild (5%) and severe (2-3%) disability was observed for the Belgian population aged 15years or older between 1997 and 2008. Arthritis was the most important contributor in women with mild and severe disability. In men, low back pain and chronic respiratory diseases contributed most to the mild and severe disability burden, respectively. The contribution also differed by age: for mild disability, depression and chronic respiratory diseases were important contributors among young individuals, while heart attack had a large contribution for older individuals. For severe disability, neurological diseases and stroke presented a large contribution in young and elderly individuals, respectively. Conclusions: Our results indicate that the assessment of the contribution of chronic diseases on disability is more informative if different levels of disability are taken into consideration. The identification of diseases which are related to different levels of disability - mild and severe - can assist policymakers in the definition and prioritisation of strategies to tackle disability, involving prevention, rehabilitation programs, support services, and training for disabled individuals

Contribution of chronic diseases to the disability burden in a population 15 years and older, Belgium, 1997-2008

Background: Age-associated disability reduces quality of life in older populations and leads to wide-range implications for social and health policy. The identification of diseases that contribute to the disability burden is crucial to the development of prevention and intervention strategies to reduce disability. In this study, we assessed the contribution of chronic diseases to the prevalence of disability in Belgium. Methods: Data from 35,837 individuals aged 15 years or older who participated in the 1997, 2001, 2004, or 2008 Belgian Health Interview Surveys were used. Disability was defined as difficulties in doing at least one of six activities of daily living (transfer in and out of bed, transfer in and out of chair, dressing, washing hands and face, feeding, and going to the toilet) and/or mobility limitations (ability to walk without stopping less than 200 m). Multiple additive regression models were fitted separately for men and women to estimate the age-specific background disability rate (experienced by everyone, independent of the presence of specific diseases) and disease-specific disability rates (disability rate in subjects who reported selected chronic diseases). Results: Musculoskeletal, cardiovascular, and respiratory diseases were the main contributors to the disability burden in Belgium. Musculoskeletal diseases were the most prevalent diseases in men and women in all age groups. Neurological diseases and stroke were the most disabling diseases, i.e. caused the highest level of disability among the diseased individuals, in all age groups for men and women, respectively. Back pain was the main cause of disability in men aged 15 to 64 years, while heart attack was the major contributor to the disability prevalence in men aged 65 or older. Likewise, arthritis was the main cause of disability among women across all age groups. Depression was also an important contributor in young subjects (15-54 years). Cancer was not an important contributor to the disability prevalence in Belgium. Conclusions: To reduce the burden of disability in Belgium, interventions should target musculoskeletal, cardiovascular and respiratory diseases especially among elderly. Furthermore, attention should also be given to depression in young individuals

Morphological and Chemical Investigation of Ovarian Structures in a Bovine Model by Contrast-Enhanced X-ray Imaging and Microscopy

An improved understanding of an ovary’s structures is highly desirable to support advances in folliculogenesis knowledge and reproductive medicine, with particular attention to fertility preservation options for prepubertal girls with malignant tumors. Although currently the golden standard for structural analysis is provided by combining histological sections, staining, and visible 2D microscopic inspection, synchrotron radiation phase-contrast microtomography is becoming a new challenge for three-dimensional studies at micrometric resolution. To this aim, the proper use of contrast agents can improve the visualization of internal structures in ovary tissues, which normally present a low radiopacity. In this study, we report a comparison of four staining protocols, based on iodine or tungsten containing agents, applied to bovine ovarian tissues fixed in Bouin’s solution. The microtomography (microCT) analyses at two synchrotron facilities under different set-ups were performed at different energies in order to maximize the image contrast. While tungsten-based agents allow large structures to be well identified, Iodine ones better highlight smaller features, especially when acquired above the K-edge energy of the specific metal. Further scans performed at lower energy where the setup was optimized for overall quality and sensitivity from phase-contrast still provided highly resolved visualization of follicular and intrafollicular structures at different maturation stages, independent of the staining protocol. The analyses were complemented by X-ray Fluorescence mapping on 2D sections, showing that the tungsten-based agent has a higher penetration in this type of tissues

Virtual histological assessment of the prenatal life history and age at death of the Upper Paleolithic fetus from Ostuni (Italy)

The fetal remains from the Ostuni 1 burial (Italy, ca 27 ka) represent a unique opportunity to explore the prenatal biological parameters, and to reconstruct the possible patho-biography, of a fetus (and its mother) in an Upper Paleolithic context. Phase-contrast synchrotron X-ray microtomography imaging of two deciduous tooth crowns and microfocus CT measurements of the right hemimandible of the Ostuni 1b fetus were performed at the SYRMEP beamline and at the TomoLab station of the Elettra - Sincrotrone laboratory (Trieste, Italy) in order to refne age at death and to report the enamel developmental history and dental tissue volumes for this fetal individual. The virtual histology allowed to estimate the age at death of the fetus at 31–33 gestational weeks. Three severe physiological stress episodes were also identifed in the prenatal enamel. These stress episodes occurred during the last two months and half of pregnancy and may relate to the death of both individuals. Compared with modern prenatal standards, Os1b’s skeletal development was advanced. This cautions against the use of modern skeletal and dental references for archaeological fnds and emphasizes the need for more studies on prenatal archaeological skeletal samples