Rock of Ages : use of the South Molle Island Quarry, Whitsunday Islands, and the implications for Holocene technological change in Australia

There is evidence to suggest that the South Molle Island stone quarry, in the Whitsunday Islands, central Queensland coast, has been used by the indigenous inhabitants of the region from at least 9,000 BP to the present. Distribution of stone from the quarry extends for at least 170km along the coast, from Abbott Point in the north to the Repulse Islands in the south. A comprehensive technological characterisation of the quarry has demonstrated that a range of manufacturing behaviours was conducted on-site, including the initial extraction of the raw material, through to the final stages of artefact retouch. The systematic production of backed artefacts is included among this suite of technological practice. This research has demonstrated that the antiquity of backed artefacts and the timing of high production rates of backed artefact manufacture occurs earlier in the Whitsunday region than elsewhere in southern Australia. In the Whitsunday Islands backed artefact production has been shown to be present from the start of the Holocene and to have been a key technological element in the early Holocene. A new understanding of backing technologies in Australia can be developed in light of this recognition of regional variation. A risk-oriented model of Holocene technological change in the Whitsunday region is presented here, as well as a discussion of the implications for wider coastal and island technological systems throughout the Holocene

A novel systems biology approach to evaluate mouse models of late-onset Alzheimer\u27s disease.

BACKGROUND: Late-onset Alzheimer\u27s disease (LOAD) is the most common form of dementia worldwide. To date, animal models of Alzheimer\u27s have focused on rare familial mutations, due to a lack of frank neuropathology from models based on common disease genes. Recent multi-cohort studies of postmortem human brain transcriptomes have identified a set of 30 gene co-expression modules associated with LOAD, providing a molecular catalog of relevant endophenotypes. RESULTS: This resource enables precise gene-based alignment between new animal models and human molecular signatures of disease. Here, we describe a new resource to efficiently screen mouse models for LOAD relevance. A new NanoString nCounter® Mouse AD panel was designed to correlate key human disease processes and pathways with mRNA from mouse brains. Analysis of the 5xFAD mouse, a widely used amyloid pathology model, and three mouse models based on LOAD genetics carrying APOE4 and TREM2*R47H alleles demonstrated overlaps with distinct human AD modules that, in turn, were functionally enriched in key disease-associated pathways. Comprehensive comparison with full transcriptome data from same-sample RNA-Seq showed strong correlation between gene expression changes independent of experimental platform. CONCLUSIONS: Taken together, we show that the nCounter Mouse AD panel offers a rapid, cost-effective and highly reproducible approach to assess disease relevance of potential LOAD mouse models

Nondisjunction and transmission ratio distortion ofChromosome 2 in a (2.8) Robertsonian translocation mouse strain

Aneuploidy results from nondisjunction of chromosomes in meiosis and is the leading cause of developmental disabilities and mental retardation in humans. Therefore, understanding aspects of chromosome segregation in a genetic model is of value. Mice heterozygous for a (2.8) Robertsonian translocation were intercrossed with chromosomally normal mice and Chromosome 2 was genotyped for number and parental origin in 836 individuals at 8.5 dpc. The frequency of nondisjunction of this Robertsonian chromosome is 1.58%. Trisomy of Chromosome 2 with two maternally derived chromosomes is the most developmentally successful aneuploid karyotype at 8.5 dpc. Trisomy of Chromosome 2 with two paternally derived chromosomes is developmentally delayed and less frequent than the converse. Individuals with maternal or paternal uniparental disomy of Chromosome 2 were not detected at 8.5 dpc. Nondisjunction events were distributed randomly across litters, i.e., no evidence for clustering was found. Transmission ratio distortion is frequently observed in Robertsonian chromosomes and a bias against the transmission of the (2.8) Chromosome was detected. Interestingly, this was observed for female and male transmitting parents

Targeting patient recovery priorities in degenerative cervical myelopathy:design and rationale for the RECEDE-Myelopathy trial-study protocol

Introduction: Degenerative cervical myelopathy (DCM) is a common and disabling condition of symptomatic cervical spinal cord compression secondary to degenerative changes in spinal structures leading to a mechanical stress injury of the spinal cord. RECEDE-Myelopathy aims to test the disease-modulating activity of the phosphodiesterase 3/phosphodiesterase 4 inhibitor Ibudilast as an adjuvant to surgical decompression in DCM. Methods and analysis: RECEDE-Myelopathy is a multicentre, double-blind, randomised, placebo-controlled trial. Participants will be randomised to receive either 60-100 mg Ibudilast or placebo starting within 10 weeks prior to surgery and continuing for 24 weeks after surgery for a maximum of 34 weeks. Adults with DCM, who have a modified Japanese Orthopaedic Association (mJOA) score 8-14 inclusive and are scheduled for their first decompressive surgery are eligible for inclusion. The coprimary endpoints are pain measured on a visual analogue scale and physical function measured by the mJOA score at 6 months after surgery. Clinical assessments will be undertaken preoperatively, postoperatively and 3, 6 and 12 months after surgery. We hypothesise that adjuvant therapy with Ibudilast leads to a meaningful and additional improvement in either pain or function, as compared with standard routine care. Study design: Clinical trial protocol V.2.2 October 2020. Ethics and dissemination: Ethical approval has been obtained from HRA - Wales. The results will be presented at an international and national scientific conferences and in a peer-reviewed journals.Trial registration number: ISRCTN Number: ISRCTN16682024.</p

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

Germ-cell nondisjunction in testes biopsies of men with idiopathic infertility.

Intracytoplasmic sperm injection (ICSI) has been used in combination with testicular sperm extraction to achieve pregnancies in couples with severe male-factor infertility, yet many of the underlying genetic mechanisms remain largely unknown. To investigate nondisjunction in mitotic and meiotic germ cells, we performed three-color FISH to detect numeric chromosome aberrations in testicular tissue samples from infertile men confirmed to have impaired spermatogenesis of unknown cause. FISH was employed to determine the rate of sex-chromosome aneuploidy in germ cells. Nuclei were distinguished as haploid or diploid, respectively. The overall incidence of sex-chromosome aneuploidy in germ cells was found to be significantly higher (P<.00001) in all three abnormal histopathologic patterns (range 39.0%-43.5%) as compared with normal controls (29.1%). The relative ratio of normal to aneuploid nuclei in the diploid cells of patients with impaired spermatogenesis was approximately 1.0, a >300% decrease when compared with the 4.42 ratio detected in patients with normal spermatogenesis. These results provide direct evidence of an increased incidence of sex-chromosome aneuploidy observed in germ cells of men with severely impaired spermatogenesis who might be candidates for ICSI with sperm obtained directly from the testis. The incidence of aneuploidy was significantly greater among the diploid nuclei, which suggests that chromosome instability is a result of altered genetic control during mitotic cell division and proliferation during spermatogenesis

Approche interdisciplinaire de la chronologie relative de sites d'art rupestre en terre d'Arhnem (Australie)

PosterLes sites d'art rupestre de la Terre d'Arnhem (Northern Territory, Australie) sont les témoins de l'occupation de ce territoire sur plusieurs dizaines de milliers d'années par les ancêtres des communautés aborigènes. Leur étude permet de mieux connaitre la culture et l'histoire de ces sociétés et l'antiquité de certains de ces sites (plus de 40 000 ans) laisse entrevoir la possibilité de préciser l'histoire du peuplement du continent australien [1]. C'est dans cette optique, et à l'instigation de la communauté Jawoyn, que le programme de recherche Connecting Country a été mis en place par l'université de Monash autour d'une équipe interdisciplinaire et internationale (Australie, Nouvelle-Zélande, France) [2]. La très grande difficulté de dater directement les peintures des abris-sous-roche de la Terre d'Arnhem a motivé l'élaboration d'une méthode de reconstitution de la chronologie relative des représentations rupestres. Cette méthode fait appel à des indices provenant de l'étude de l'art, de la géomorphologie des parois, de l'archéologie du sol et de comparaisons avec les sites voisins. En combinant l'analyse stratigraphique des représentations graphiques, la caractérisation physico-chimique des pigments - in-situ avec des techniques portables non-destructives ou en laboratoire sur microéchantillons - l'analyse des artéfacts et colorants trouvés en fouille, l'étude du support rocheux et des mécanismes d'altération de la roche et des pigments, il est possible de proposer une première esquisse de la chronologie relative des interventions humaines sur les parois des sites étudiés et des événements naturels les ayant affectées

High-resolution palaeoclimatic records for the last millennium: Interpretation, integration and comparison with General Circulation Model control-run temperatures

Palaeoclimatology provides our only means of assessing climatic variations before the beginning of instrumental records. The various proxy variables used, however, have a number of limitations which must be adequately addressed and understood. Besides their obvious spatial and seasonal limitations, different proxies are also potentially limited in their ability to represent climatic variations over a range of different timescales. Simple correlations with instrumental data over the period since AD 1881 give some guide to which are the better proxies, indicating that coral- and ice-core-based reconstructions are poorer than tree-ring and historical ones. However, the quality of many proxy time series can deteriorate during earlier times. Suggestions are made for assessing proxy quality over longer periods than the last century by intercomparing neighbouring proxies and, by comparisons with less temporally resolved proxies such as borehole temperatures. We have averaged 17 temperature reconstructions (representing various seasons of the year), all extending back at least to the mid-seventeenth century, to form two annually resolved hemispheric series (NH10 and SH7). Over the 1901-91 period, NH10 has 36% variance in common with average NH summer (June to August) temperatures and 70% on decadal timescales. SH7 has 16% variance in common with average SH summer (December to February) temperatures and 49% on decadal timescales, markedly poorer than the reconstructed NH series. The coldest year of the millennium over the NH is AD 1601, the coldest decade 1691-1700 and the seventeenth is the coldest century. A Principal Components Analysis (PCA) is performed on yearly values for the 17 reconstructions over the period AD 1660-1970. The correlation between PC1 and NH10 is 0.92, even though PC1 explains only 13.6% of the total variance of all 17 series. Similar PCA is performed on thousand-year-long General Circulation Model (GCM) data from the Geophysical Fluid Dynamics Laboratory (GFDL) and the Hadley Centre (HADCM2), sampling these for the same locations and seasons as the proxy data. For GFDL, the correlation between its PC1 and its NH10 is 0,89, while for HADCM2 the PCs group markedly differently. Cross-spectral analyses are performed on the proxy data and the GFDL model data at two different frequency bands (0.02 and 0.03 cycles per year). Both analyses suggest that there is no large-scale coherency in the series on these timescales. This implies that if the proxy data are meaningful, it should be relatively straightforward to detect a coherent near-global anthropogenic signal in surface temperature data