Sedimentological evidence for rooting structures in the Early Devonian Anglo-Welsh Basin (UK), with speculation on their producers

Rooting structures preserved as casts in alluvial deposits of the Lower Devonian Lower Old Red Sandstone occur more extensively than previously thought in the Anglo-Welsh Basin. Two rooting structure morphotypes are identified: morphotype 1 being predominantly horizontal, and morphotype 2 comprising vertical forms. Both morphotypes taper along their length, are oval in cross-section, branch, and can be linear or sinuous. Fills are heterolithic in nature. The rooting structures are observed in sediments deposited in a wide variety of environments including both low-sinuosity within-channel bar-tops and accretionary bar surfaces (inclined-heterolithic stratification); accretionary banks of sinuous ephemeral channels (inclined-heterolithic stratification); floodplains (including margins of shallow floodplain ponds) of both ephemeral and perennial river channels, and well-developed calcic Vertisols. Although a vascular plant origin to the rooting structures cannot be discounted, there is circumstantial evidence that the structures were produced by the enigmatic Prototaxites, recently reinterpreted as a giant fungus. It is possible that they represent underground aggregates (rhizomorphs or cords) of hyphae involved in anchorage and nutrient foraging. Organic matter associated with biofilms and crusts is hypothesized as a source of nutrients for the presumed saprotroph.     

The influence of IL-1 treatment on the reconstitution of the hemopoietic and immune systems after sublethal radiation

The influence of IL-1 administration on the recovery of the hemopoietic and immune systems from sublethal irradiation was assessed. Mice were irradiated (750 R) and injected twice daily with purified recombinant derived IL-1 beta (200 ng/injection). At various times after irradiation, the functional capacity of the hemopoietic and immune systems was determined. It was found that IL-1 therapy resulted in a significantly greater number of granulocyte-macrophage-CSF responsive colony-forming cells in the bone marrow of the irradiated mice on days 5 and 11 postirradiation but not at later times. In addition the radiation induced neutropenia recovered quicker in the IL-1-treated mice with significantly greater numbers of peripheral blood granulocytes being seen on days 15 and 20 after irradiation. The influence of IL-1 therapy on the recovery of the immune system was also assessed. Of note was the observation that mice receiving IL-1 therapy had chronically hypoplastic thymi. Although thymic cellularity increased with time after irradiation in the control mice, there was no such increase in the IL-1-treated mice. Similarly, the number of pre-B cells in the marrow of these mice was also diminished. Thus, in the IL-1-treated mice the regeneration of the peripheral immune function was retarded, characterized by a general lymphopenia and decreased splenic responses to mitogenic stimuli.     

Arsenic-induced exencephaly in the mouse and associated lesions occurring during neurulation

Early tissue damage following a teratogenic dose of arsenic to the dam was studied in mice with the objective of detecting the primary lesion associated with the development of exencephaly. Animals were killed 6 to 21 h after a single 45 mg/kg intraperitoneal injection of sodium arsenate on day 8 of pregnancy and neurulation-stage embryos were fixed for histological and ultrastructural examination. In the prospective hindbrain, the most consistent feature associated with arsenate treatment was the widely separated neural folds which were not positioned for closure. Intracytoplasmic inclusions, interpreted as necrotic debris, were most numerous in the apical portion of the neural folds, sometimes extending into the mesenchyme, but they were not extensive in most embryos. In the prospective forebrain, necrotic debris was found throughout the neuroepithelium, in contrast to the posterior portions of the developing brain. It is not clear that necrosis of the neuroepithelium or mesenchyme would in itself be the primary lesion associated with exencephaly, although death of specific cells such as those participating in the fusion process could be involved. The potential effect of arsenate on physiological and biochemical processes which could affect neural tube closure is discussed.     

Alterations in megakaryocyte and platelet compartments following in vivo IL-1 beta administration to normal mice

IL-1 has been shown to stimulate the release of granulocyte-macrophage CSF, granulocyte-CSF, and macrophage-CSF from "accessory cell populations" in vitro, and it stimulates the appearance of colony-stimulating activity in the sera of mice in vivo. This cytokine has also been proposed to act on primitive hematopoietic progenitor cells to stimulate expression of receptors for the CSF. We sought to determine whether IL-1 beta could influence platelet and/or megakaryocytes and their progenitor cells following in vivo administration to normal mice. Our results demonstrated that, although administration of IL-1 beta clearly expands the pool of megakaryocyte-CFU and acetylcholinesterase-positive megakaryocytic cells (primarily in the spleen), it causes a transient and dose-dependent reduction of circulating platelets. The associated thrombocytopenia can be abolished by splenectomy before IL-1 beta administration, and is not temporally associated with the development of splenomegaly.     

A high-throughput screen to identify novel calcineurin inhibitors

Calcineurin is a eukaryotic protein phosphatase important for many signalling and developmental processes in cells. Inhibitors of this enzyme are used clinically and there is interest in identifying novel inhibitors for therapeutic applications. This report describes a high-throughput assay that can be used to screen natural or chemical libraries of compounds to identify new calcineurin inhibitors. The microtitre plate assay is based on a yeast reporter strain and was validated with known inhibitors and tested in a pilot screen of bacterial extracts.     

Correlates of knee extensor training load used in rehabilitation after knee surgery

Resistance training is one of the major components of rehabilitation after musculoskeletal injury and surgery. Despite the importance of resistance training and the frequency of its use in rehabilitation, little is known about factors that are related to training load that might be useful in devising and monitoring training in a patient and comparing training intensities between individuals and groups. We hypothesized that the following would show a statistically significant relationship to training load: injury chronicity, self-assessed knee function (Hughston Clinic questionnaire), knee swelling (injured-uninjured midpatellar knee girth), uninjured knee girth, and body mass. The purpose of this study was to evaluate whether factors such as body mass are related to the load used in training the knee extensors in rehabilitation after knee surgery. Thirty-six individuals undergoing early-phase rehabilitation after knee arthroscopic meniscectomy surgery participated in this study. Subjects were tested 5 days after surgery, just prior to commencing a 6-week outpatient rehabilitation program, and again soon after the end of this rehabilitation program. The independent variables evaluated were age, gender, body mass, meniscus injured, injury chronicity, knee function self-assessment, knee swelling (injured-uninjured midpatellar girth), uninjured knee girth, and knee flexion and extension passive range of motion (difference between injured and uninjured side). The dependent variable was the load used for training the knee extensors on the knee extension machine in the final training session prior to the posttest. The only variable exhibiting a statistically significant (p = 0.001) relationship to knee extensor final training was age (r = -0.529). This finding, that age was the only variable to have a significant relationship with training load, suggests that clinicians' expectation of training intensity should decrease with an increase in the patient's age in the range studied (20-58 years) for patients recovering from knee arthroscopic meniscectomy.     

Biochemical Association of Metabolic Profile and Microbiome in Chronic Pressure Ulcer Wounds

Chronic, non-healing wounds contribute significantly to the suffering of patients with co-morbidities in the clinical population with mild to severely compromised immune systems. Normal wound healing proceeds through a well-described process. However, in chronic wounds this process seems to become dysregulated at the transition between resolution of inflammation and re-epithelialization. Bioburden in the form of colonizing bacteria is a major contributor to the delayed headlining in chronic wounds such as pressure ulcers. However how the microbiome influences the wound metabolic landscape is unknown. Here, we have used a Systems Biology approach to determine the biochemical associations between the taxonomic and metabolomic profiles of wounds colonized by bacteria. Pressure ulcer biopsies were harvested from primary chronic wounds and bisected into top and bottom sections prior to analysis of microbiome by pyrosequencing and analysis of metabolome using 1H nuclear magnetic resonance (NMR) spectroscopy. Bacterial taxonomy revealed that wounds were colonized predominantly by three main phyla, but differed significantly at the genus level. While taxonomic profiles demonstrated significant variability between wounds, metabolic profiles shared significant similarity based on the depth of the wound biopsy. Biochemical association between taxonomy and metabolic landscape indicated significant wound-to-wound similarity in metabolite enrichment sets and metabolic pathway impacts, especially with regard to amino acid metabolism. To our knowledge, this is the first demonstration of a statistically robust correlation between bacterial colonization and metabolic landscape within the chronic wound environment.