Mass extinctions drove increased global faunal cosmopolitanism on the supercontinent Pangaea

Mass extinctions have profoundly impacted the evolution of life through not only reducing taxonomic diversity but also reshaping ecosystems and biogeographic patterns. In particular, they are considered to have driven increased biogeographic cosmopolitanism, but quantitative tests of this hypothesis are rare and have not explicitly incorporated information on evolutionary relationships. Here we quantify faunal cosmopolitanism using a phylogenetic network approach for 891 terrestrial vertebrate species spanning the late Permian through Early Jurassic. This key interval witnessed the Permian–Triassic and Triassic–Jurassic mass extinctions, the onset of fragmentation of the supercontinent Pangaea, and the origins of dinosaurs and many modern vertebrate groups. Our results recover significant increases in global faunal cosmopolitanism following both mass extinctions, driven mainly by new, widespread taxa, leading to homogenous ‘disaster faunas’. Cosmopolitanism subsequently declines in post-recovery communities. These shared patterns in both biotic crises suggest that mass extinctions have predictable influences on animal distribution and may shed light on biodiversity loss in extant ecosystems

A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome

Down syndrome, caused by an extra copy of chromosome 21, is associated with a greatly increased risk of early onset Alzheimer disease. It is thought that this risk is conferred by the presence of three copies of the gene encoding amyloid precursor protein (APP), an Alzheimer risk factor, although the possession of extra copies of other chromosome 21 genes may also play a role. Further study of the mechanisms underlying the development of Alzheimer disease in Down syndrome could provide insights into the mechanisms that cause dementia in the general population

Inter- and intraobserver reliability of the MTM-classification for proximal humeral fractures: A prospective study

<p>Abstract</p> <p>Background</p> <p>A precise modular topographic-morphological (MTM) classification for proximal humeral fractures may address current classification problems. The classification was developed to evaluate whether a very detailed classification exceeding the analysis of fractured parts may be a valuable tool.</p> <p>Methods</p> <p>Three observers classified plain radiographs of 22 fractures using both a simple version (fracture displacement, number of parts) and an extensive version (individual topographic fracture type and morphology) of the MTM classification. Kappa-statistics were used to determine reliability.</p> <p>Results</p> <p>An acceptable reliability was found for the simple version classifying fracture displacement and fractured main parts. Fair interobserver agreement was found for the extensive version with individual topographic fracture type and morphology.</p> <p>Conclusion</p> <p>Although the MTM-classification covers a wide spectrum of fracture types, our results indicate that the precise topographic and morphological description is not delivering reproducible results. Therefore, simplicity in fracture classification may be more useful than extensive approaches, which are not adequately reliable to address current classification problems.</p

Development and validation of a paediatric long-bone fracture classification. A prospective multicentre study in 13 European paediatric trauma centres

Background: The aim of this study was to develop a child-specific classification system for long bone fractures and to examine its reliability and validity on the basis of a prospective multicentre study. Methods: Using the sequentially developed classification system, three samples of between 30 and 185 paediatric limb fractures from a pool of 2308 fractures documented in two multicenter studies were analysed in a blinded fashion by eight orthopaedic surgeons, on a total of 5 occasions. Intra- and interobserver reliability and accuracy were calculated. Results: The reliability improved with successive simplification of the classification. The final version resulted in an overall interobserver agreement of kappa=0.71 with no significant difference between experienced and less experienced raters. Conclusions: In conclusion, the evaluation of the newly proposed classification system resulted in a reliable and routinely applicable system, for which training in its proper use may further improve the reliability. It can be recommended as a useful tool for clinical practice and offers the option for developing treatment recommendations and outcome predictions in the future

Anti-α-Internexin Autoantibody from Neuropsychiatric Lupus Induce Cognitive Damage via Inhibiting Axonal Elongation and Promote Neuron Apoptosis

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a major complication for lupus patients, which often leads to cognitive disturbances and memory loss and contributes to a significant patient morbidity and mortality. The presence of anti-neuronal autoantibodies (aAbs) has been identified; as examples, anti-NMDA receptors and anti-Ribsomal P aAbs have been linked to certain pathophysiological features of NPSLE.In the current study, we used a proteomic approach to identify an intermediate neurofilament alpha-internexin (INA) as a pathogenetically relevant autoantigen in NPSLE. The significance of this finding was then validated in an expanded of a cohort of NPSLE patients (n = 67) and controls (n = 270) by demonstrating that high titers of anti-INA aAb was found in both the serum and cerebrospinal fluid (CSF) of ∼50% NPSLE. Subsequently, a murine model was developed by INA immunization that resulted in pronounced cognitive dysfunction that mimicked features of NPSLE. Histopathology in affected animals displayed cortical and hippocampal neuron apoptosis. In vitro studies further demonstrated that anti-INA Ab mediated neuronal damage via inhibiting axonal elongation and eventually driving the cells to apoptosis.Taken together, this study identified a novel anti-neurofilament aAb in NPSLE, and established a hitherto undescribed mechanism of aAb-mediated neuron damage that could have relevance to the pathophysiology of NPSLE

Gene Network Disruptions and Neurogenesis Defects in the Adult Ts1Cje Mouse Model of Down Syndrome

Background: Down syndrome (DS) individuals suffer mental retardation with further cognitive decline and early onset Alzheimer's disease. Methodology/Principal Findings: To understand how trisomy 21 causes these neurological abnormalities we investigated changes in gene expression networks combined with a systematic cell lineage analysis of adult neurogenesis using the Ts1Cje mouse model of DS. We demonstrated down regulation of a number of key genes involved in proliferation and cell cycle progression including Mcm7, Brca2, Prim1, Cenpo and Aurka in trisomic neurospheres. We found that trisomy did not affect the number of adult neural stem cells but resulted in reduced numbers of neural progenitors and neuroblasts. Analysis of differentiating adult Ts1Cje neural progenitors showed a severe reduction in numbers of neurons produced with a tendency for less elaborate neurites, whilst the numbers of astrocytes was increased. Conclusions/Significance: We have shown that trisomy affects a number of elements of adult neurogenesis likely to result in a progressive pathogenesis and consequently providing the potential for the development of therapies to slow progression of, or even ameliorate the neuronal deficits suffered by DS individuals.Chelsee A. Hewitt, King-Hwa Ling, Tobias D. Merson, Ken M. Simpson, Matthew E. Ritchie, Sarah L. King, Melanie A. Pritchard, Gordon K. Smyth, Tim Thomas, Hamish S. Scott and Anne K. Vos

The genetic architecture of aniridia and Gillespie syndrome

Absence of part or all of the iris, aniridia, is a feature of several genetically distinct conditions. This review focuses on iris development and then the clinical features and molecular genetics of these iris malformations. Classical aniridia, a panocular eye malformation including foveal hypoplasia, is the archetypal phenotype associated with heterozygous PAX6 loss-of-function mutations. Since this was identified in 1991, many genetic mechanisms of PAX6 inactivation have been elucidated, the commonest alleles being intragenic mutations causing premature stop codons, followed by those causing C-terminal extensions. Rarely, aniridia cases are associated with FOXC1, PITX2 and/or their regulatory regions. Aniridia can also occur as a component of many severe global eye malformations. Gillespie syndrome—a triad of partial aniridia, non-progressive cerebellar ataxia and intellectual disability—is phenotypically and genotypically distinct from classical aniridia. The causative gene has recently been identified as ITPR1. The same characteristic Gillespie syndrome-like iris, with aplasia of the pupillary sphincter and a scalloped margin, is seen in ACTA2-related multisystemic smooth muscle dysfunction syndrome. WAGR syndrome (Wilms tumour, aniridia, genitourinary anomalies and mental retardation/intellectual disability), is caused by contiguous deletion of PAX6 and WT1 on chromosome 11p. Deletions encompassing BDNF have been causally implicated in the obesity and intellectual disability associated with the condition. Lastly, we outline a genetic investigation strategy for aniridia in light of recent developments, suggesting an approach based principally on chromosomal array and gene panel testing. This strategy aims to test all known aniridia loci—including the rarer, life-limiting causes—whilst remaining simple and practical

Current concepts in locking plate fixation of proximal humerus fractures

Despite numerous available treatment strategies, the management of complex proximal humeral fractures remains demanding. Impaired bone quality and considerable comorbidities pose special challenges in the growing aging population. Complications after operative treatment are frequent, in particular loss of reduction with varus malalignment and subsequent screw cutout. Locking plate fixation has become a standard in stabilizing these fractures, but surgical revision rates of up to 25% stagnate at high levels. Therefore, it seems of utmost importance to select the right treatment for the right patient. This article provides an overview of available classification systems, indications for operative treatment, important pathoanatomic principles, and latest surgical strategies in locking plate fixation. The importance of correct reduction of the medial cortices, the use of calcar screws, augmentation with bone cement, double-plate fixation, and auxiliary intramedullary bone graft stabilization are discussed in detail