Size-Frequency Distributions along a Latitudinal Gradient in Middle Permian Fusulinoideans

Geographic gradients in body size within and among living species are commonly used to identify controls on the long-term evolution of organism size. However, the persistence of these gradients over evolutionary time remains largely unknown because ancient biogeographic variation in organism size is poorly documented. Middle Permian fusulinoidean foraminifera are ideal for investigating the temporal persistence of geographic gradients in organism size because they were diverse and abundant along a broad range of paleo-latitudes during this interval (∼275–260 million years ago). In this study, we determined the sizes of Middle Permian fusulinoidean fossils from three different paleo-latitudinal zones in order to examine the relationship between the size of foraminifers and regional environment. We recovered the following results: keriothecal fusulinoideans are substantially larger than nonkeriothecal fusulinoideans; fusulinoideans from the equatorial zone are typically larger than those from the north and south transitional zones; neoschwagerinid specimens within a single species are generally larger in the equatorial zone than those in both transitional zones; and the nonkeriothecal fusulinoideans Staffellidae and Schubertellidae have smaller size in the north transitional zone. Fusulinoidean foraminifers differ from most other marine taxa in exhibiting larger sizes closer to the equator, contrary to Bergmann's rule. Meridional variation in seasonality, water temperature, nutrient availability, and carbonate saturation level are all likely to have favored or enabled larger sizes in equatorial regions. Temporal variation in atmospheric oxygen concentrations have been shown to account for temporal variation in fusulinoidean size during Carboniferous and Permian time, but oxygen availability appears unlikely to explain biogeographic variation in fusulinoidean sizes, because dissolved oxygen concentrations in seawater typically increase away from the equator due to declining seawater temperatures. Consequently, our findings highlight the fact that spatial gradients in organism size are not always controlled by the same factors that govern temporal trends within the same clade

Linking Proteomic and Transcriptional Data through the Interactome and Epigenome Reveals a Map of Oncogene-induced Signaling

Cellular signal transduction generally involves cascades of post-translational protein modifications that rapidly catalyze changes in protein-DNA interactions and gene expression. High-throughput measurements are improving our ability to study each of these stages individually, but do not capture the connections between them. Here we present an approach for building a network of physical links among these data that can be used to prioritize targets for pharmacological intervention. Our method recovers the critical missing links between proteomic and transcriptional data by relating changes in chromatin accessibility to changes in expression and then uses these links to connect proteomic and transcriptome data. We applied our approach to integrate epigenomic, phosphoproteomic and transcriptome changes induced by the variant III mutation of the epidermal growth factor receptor (EGFRvIII) in a cell line model of glioblastoma multiforme (GBM). To test the relevance of the network, we used small molecules to target highly connected nodes implicated by the network model that were not detected by the experimental data in isolation and we found that a large fraction of these agents alter cell viability. Among these are two compounds, ICG-001, targeting CREB binding protein (CREBBP), and PKF118–310, targeting β-catenin (CTNNB1), which have not been tested previously for effectiveness against GBM. At the level of transcriptional regulation, we used chromatin immunoprecipitation sequencing (ChIP-Seq) to experimentally determine the genome-wide binding locations of p300, a transcriptional co-regulator highly connected in the network. Analysis of p300 target genes suggested its role in tumorigenesis. We propose that this general method, in which experimental measurements are used as constraints for building regulatory networks from the interactome while taking into account noise and missing data, should be applicable to a wide range of high-throughput datasets.National Science Foundation (U.S.) (DB1-0821391)National Institutes of Health (U.S.) (Grant U54-CA112967)National Institutes of Health (U.S.) (Grant R01-GM089903)National Institutes of Health (U.S.) (P30-ES002109

The UniSpacer™: correcting varus malalignment in medial gonarthrosis

While options for operative treatment of leg axis varus malalignment in patients with medial gonarthrosis include several established procedures, such as unicompartmental knee arthroplasty (UKA), total knee arthroplasty (TKA) or high tibial osteotomy (HTO), there has been little focus on a less invasive option introduced more recently: the UniSpacer™ implant, a self-centering, metallic interpositional device for the knee. This study evaluates clinical and radiological results of the UniSpacer™, whether alignment correction can be achieved by UniSpacer™ arthroplasty and alignment change in the first five postoperative years. Anteroposterior long leg stance radiographs of 20 legs were digitally analysed to assess alignment change: two relevant angles and the deviation of the mechanical axis of the leg were analysed before and after surgery. Additionally, the change of the postoperative alignment was determined one and five years postoperatively. Analysing the mechanical tibiofemoral angle, a significant leg axis correction was achieved, with a mean valgus change of 4.7 ± 1.9°; a varus change occurred in the first postoperative year, while there was no significant further change of alignment seen five years after surgery. The UniSpacer™ corrects malalignment in patients with medial gonarthrosis; however, a likely postoperative change in alignment due to implant adaptation to the joint must be considered before implantation. Our results show that good clinical and functional results can be achieved after UniSpacer™ arthroplasty. However, four of 19 knees had to be revised to a TKA or UKA due to persistent pain, which is an unacceptably high revision rate when looking at the alternative treatment options of medial osteoarthritis of the knee

Nerve Transfers for Adult Traumatic Brachial Plexus Palsy (Brachial Plexus Nerve Transfer)

Adult traumatic brachial plexus injuries can have devastating effects on upper extremity function. Although neurolysis, nerve repair, and nerve grafting have been used to treat injuries to the plexus, nerve transfer makes use of an undamaged nerve to supply motor input over a relatively short distance to reinnervate a denervated muscle. A review of several recent innovations in nerve transfer surgery for brachial plexus injuries is illustrated with surgical cases performed at this institution