Paleobiology of titanosaurs: reproduction, development, histology, pneumaticity, locomotion and neuroanatomy from the South American fossil record

Fil: García, Rodolfo A.. Instituto de Investigación en Paleobiología y Geología. Museo Provincial Carlos Ameghino. Cipolletti; ArgentinaFil: Salgado, Leonardo. Instituto de Investigación en Paleobiología y Geología. General Roca. Río Negro; ArgentinaFil: Fernández, Mariela. Inibioma-Centro Regional Universitario Bariloche. Bariloche. Río Negro; ArgentinaFil: Cerda, Ignacio A.. Instituto de Investigación en Paleobiología y Geología. Museo Provincial Carlos Ameghino. Cipolletti; ArgentinaFil: Carabajal, Ariana Paulina. Museo Carmen Funes. Plaza Huincul. Neuquén; ArgentinaFil: Otero, Alejandro. Museo de La Plata. Universidad Nacional de La Plata; ArgentinaFil: Coria, Rodolfo A.. Instituto de Paleobiología y Geología. Universidad Nacional de Río Negro. Neuquén; ArgentinaFil: Fiorelli, Lucas E.. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica. Anillaco. La Rioja; Argentin

Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference

The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique\u2014Subtype and Stage Inference (SuStaIn)\u2014able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes; further the technique reveals within-genotype heterogeneity. In Alzheimer\u2019s disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype (p = 7.18 7 10 124 ) or temporal stage (p = 3.96 7 10 125 ). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine

Predator-prey body size, interaction strength and the stability of a real food web.

1. We examined the empirical relationship between predator–prey body size ratio and interaction strength in the Ythan Estuary food web. 2. We have refined a previously published version of the food web and explored how size-based predatory effects might affect food web dynamics. To do so, we used four predatory species Crangon crangon (Linnaeus), Carcinus maenas (Linnaeus), Pomatoschistus microps (Krøyer) and Platichthys flesus (Linnaeus) and one common prey species Corophium volutator (Pallas) from the food web. 3. All predators and prey were sorted into small, medium and large size classes and placed into mesocosms in all possible pairwise combinations of size and species identity to determine per capita effects of predators on prey (aij). 4. Using Lotka–Volterra dynamics the empirical body size relationships obtained from these experiments and other relationships already available for the Ythan Estuary, we parameterized a food web model for this system. The local stability properties of the resulting food web models were then determined. 5. We found that by choosing interaction strengths using an empirically defined scaling law, the resulting food web models are always dynamically stable, despite the residual uncertainties in the modelling approach. This contrasts with the statistical expectation that random webs with random parameters have a vanishingly improbable chance of stability. 6. The patterning of predator and prey body sizes in real ecosystems affects the arrangement of interaction strengths, which in turn determines food web stability

Reconstruction of Middle Jurassic dinosaur-dominated communities from the vertebrate ichnofauna of the Cleveland Basin of Yorkshire, UK

Globally, skeletal remains of dinosaurs are particularly rare throughout much of the Middle Jurassic. Thus, other sources of evidence, and most importantly ichnofaunas, are important indicators of the contemporary terrestrial vertebrate communities. The outcrops of the Ravenscar Group (Aalenian-Bajocian) within the Cleveland Basin of Yorkshire, UK, which have recently been recognised as a megatracksite of global significance, provide one such major source of ichnofaunal information of this age. A comprehensive database on the variety and occurrence of dinosaur and other vertebrate traces within the Ravenscar Group has been built from a long-term and detailed study of the sequence. Thirty different and distinct morphotypes of vertebrate traces have been recognised and are being analysed and further differentiated morphometrically. Some of the morphotypes represent behavioural, preservational and perhaps ontogenetic variants of other morphotypes, but nevertheless the range of quadrupedal and bipedal prints allows an overall fauna of sauropod, stegosaurian, ornithopod and theropod dinosaurs along with crocodiles, pond turtles and fish to be reconstructed. The distribution and abundance of prints and print types within the succession shows evidence of environmental control on the behaviour and distribution of the vertebrates. Case studies highlight both the advantages and disadvantages of this type of data in reconstructing palaeocommunities

Paleobiología de Titanosaurios de Sudamérica: reproducción, desarrollo, histología, neumaticidad, locomoción y neuroanatomía

Much of the current paleobiological knowledge on titanosaur sauropods was attained in just the last fifteen years, in particular that related to reproductive and developmental biology. Recent years have also seen progress on other poorly explored topics, such as pneumaticity, muscle architecture and locomotion, and endocast reconstruction and associated structures. Some titanosaurs laid numerous, relatively small Megaloolithidae eggs (with diameters ranging from 12 to 14 cm) in nests dug In the ground and, as known from the South American records, probably eggs of the multispherulitic morphotype. During ontogeny, certain titanosaurs displayed some variations in cranial morphology, some of them likely associated with the differing feeding habits between hatchlings and adults. The bone tissue of some adult titanosaurs was rapidly and cyclically deposited and shows a greater degree of remodeling than in other sauropods. Saltasaurines in particular show evidence of postcranial skeletal pneumaticity in both axial and appendicular skeleton, providing clues about soft tissue anatomy and the structure of the respiratory system. Titanosaurs, like all sauropods, were characterized by being fully quadrupedal, although some appendicular features and putative trackways indicate that their stance was not as columnar as in other sauropods. These anatomical peculiarities are significantly developed In saltasaurines, a derived group of titanosaurs. Compared with other sauropods, some titanosaurs seem to have had very poor olfaction but would have been capable of capturing sounds In a relatively wide range of high frequencies, although not to the extent of living birds.El conocimiento paleobiológico de los saurópodos titanosaurios, particularmente su reproducción y biología del desarrollo, fue alcanzado recién en los últimos quince años. En estos últimos años también se ha avanzado en temas poco explorados hasta el momento, como la neumatización, su arquitectura muscular y locomoción y la reconstrucción de partes blandas como el cerebro y estructuras asociadas. Algunos titanosaurios depositan sus numerosos y pequeños huevos megaloolitidos en nidos excavados sobre el suelo. Durante la ontogenia ciertos titanosaurios exponen algunas variaciones en su morfología craneana, algunas de estas probablemente asociadas con las diferentes maneras de alimentarse que tendrían los juveniles y los adultos. El tejido óseo de algunos titanosaurios adultos se habría depositado rápido y cíclicamente, exponiendo una mayor remodelación que en otros saurópodos. Los titanosaurios, particularmente los saltasaurinos, exponen una neumaticidad postcraneal en el esqueleto axial y apendicular, este carácter permite Inferir la anatomía de sus tejidos blandos y de su sistema respiratorio. Los titanosaurios, como todos los saurópodos, estaban caracterizados por ser cuadrúpedos, aunque algunos caracteres apendiculares y las huellas indican que su postura no habría sido tan columnar como en otros saurópodos. Aquellas peculiaridades anatómicas están notoriamente desarrolladas en los saltasaurinos, un grupo de titanosaurios derivados. Comparado con otros saurópodos, algunos titanosaurios parecen haber tenido un pobre sentido del olfato, sin embargo estos habrían tenido la capacidad de captar sonidos de alta frecuencia en un rango relativamente amplio, aunque no tanto como las aves actuales.Fil: Garcia, Rodolfo Andres. Provincia de Río Negro. Museo Provincial “Carlos Ameghino”. Instituto de Investigación en Paleobiología y Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Salgado, Leonardo. Provincia de Río Negro. Instituto de Investigación en Paleobiología y Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fernández, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Patagonia Norte. Instituto de Investigación en Biodiversidad y Medioambiente; Argentina. Universidad Nacional del Comahue. Centro Regional Universitario Bariloche; ArgentinaFil: Cerda, Ignacio Alejandro. Provincia de Río Negro. Museo Provincial “Carlos Ameghino”. Instituto de Investigación en Paleobiología y Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Paulina Carabajal, Ariana. Provincia del Neuquen. Municipalidad de Plaza Huincul. Museo "Carmen Funes"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Otero, Alejandro. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Departamento Científico de Paleontología de Vertebrados; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Coria, Rodolfo Anibal. Universidad Nacional de Rio Negro. Sede Alto Valle. Instituto de Investigaciones en Paleobiologia y Geologia; Argentina. Provincia del Neuquen. Municipalidad de Plaza Huincul. Museo "Carmen Funes"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fiorelli, Lucas Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Regional de Investigaciones Cientificas y Transferencia Tecnológica de Anillaco; Argentin