Innate Immunity: A Balance between Disease and Adaption to Stress

Since first being documented in ancient times, the relation of inflammation with injury and disease has evolved in complexity and causality. Early observations supported a cause (injury) and effect (inflammation) relationship, but the number of pathologies linked to chronic inflammation suggests that inflammation itself acts as a potent promoter of injury and disease. Additionally, results from studies over the last 25 years point to chronic inflammation and innate immune signaling as a critical link between stress (exogenous and endogenous) and adaptation. This brief review looks to highlight the role of the innate immune response in disease pathology, and recent findings indicating the innate immune response to chronic stresses as an influence in driving ad-aptation

Adaptive Synaptogenesis Constructs Neural Codes That Benefit Discrimination

Intelligent organisms face a variety of tasks requiring the acquisition of expertise within a specific domain, including the ability to discriminate between a large number of similar patterns. From an energy-efficiency perspective, effective discrimination requires a prudent allocation of neural resources with more frequent patterns and their variants being represented with greater precision. In this work, we demonstrate a biologically plausible means of constructing a single-layer neural network that adaptively (i.e., without supervision) meets this criterion. Specifically, the adaptive algorithm includes synaptogenesis, synaptic shedding, and bi-directional synaptic weight modification to produce a network with outputs (i.e. neural codes) that represent input patterns proportional to the frequency of related patterns. In addition to pattern frequency, the correlational structure of the input environment also affects allocation of neural resources. The combined synaptic modification mechanisms provide an explanation of neuron allocation in the case of self-taught experts

Review of: "Blocking a dead-end assembly pathway creates a point of regulation for the DEAD-box ATPase Has1 and prevents platform misassembly"

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Effects of Diets Containing Soybean Hulls or Rolled Corn on the Performance and Mineral Status of Newly Received Calves

The objective of this study was to determine the effectiveness of soybean hulls as an energy source for newly received feeder calves and their effects on ADG, DMI, gain/feed (G/F), morbidity rate and mineral status. Steers from a single source were blocked into previously weaned (PW; n = 63; BW = 265 ± 2.9 kg) and non-weaned (NW; n = 92; BW = 264 ± 2.4 kg) groups, then allotted to one of two dietary treatment groups. Diets consisted of either rolled corn (CRN) or soybean hulls (SBH), and oat silage and vitamin/mineral supplements. Liver biopsies and blood samples were collected at the initiation of the trial and again after 28 d on feed. Steers fed CRN had lower (P \u3c 0.10) ADG through d 28 compared to SBH. Previously weaned steers had a higher (P \u3c 0.10) ADG than NW steers through d 28. The SBH diets caused higher (P \u3c 0.01) DMI through d 28 and overall. There was a diet × weaning group interaction (P \u3c 0.10) for DMI through d 28. Cumulative feed/gain (F/G) was lower (P \u3c 0.05) for cattle fed CRN diets. Liver Cu concentrations decreased (P \u3c 0.01) by 22% in steers fed SBH, but were unchanged in steers fed CRN diets. Previously weaned steers had a greater loss of liver Cu compared to NW steers (P \u3c 0.01). Liver Zn concentration was affected by a diet × weaning group interaction (P \u3c 0.05). Morbidity rate (6.5%) was not affected by treatments. These results suggest the use of soybean hulls in newly received calf diets has the potential to stimulate DMI, and that Cu and Zn in soybean hulls may have limited availability

From interaction to function: Phospholipase C beta 1 protects cells from stress-induced apoptosis

The phosphoinositide-dependent signal transduction pathway has been implicated in the control of a variety of biological processes, such as the regulation of cellular metabolism and omeostasis, cell proliferation and differentiation. One of the key player in the regulation of inositol lipid signaling is phospholipase C beta 1 (PI-PLCβ1), which hydrolyses PtIns(4,5)P2, giving rise to the second messengers IP3 and DAG. The complete mapping of the PI-PLCβ1 interactome was undertaken, to understand its diverse functions within the nuclear compartment and to determine its contribution to physiological and pathological processes. Affinity purification-mass spectrometry (AP-MS) allowed for the identification of 160 proteins present in association with PI-PLCβ1 in the nucleus of erythroleukemia cells. Co-immunoprecipitation analysis of selected proteins confirmed the data obtained from mass spectrometry. Of particular interest was the identification of proteins involved in nuclear trafficking, as well as factors involved in hematological malignancies and several anti-apoptotic proteins (Piazzi et al., 2013). PI-PLCβ1 has been associated with the regulation of several cellular functions, some of which are not yet fully understood. In particular, it has been reported that PI-PLCβ1 protects murine fibroblasts from oxidative stress-induced cell death, through signaling events which remain unclear. Reactive oxygen species (ROS) have been shown to regulate major epigenetic processes causing the silencing of tumor suppressors and enhancing the proliferation of leukemic cells under oxidative stress. Investigation of the role for ROS and their signaling mediators in the pathogenesis of leukemia might, therefore, outline innovative approaches for the improvement of pharmacological therapies to treat leukemia. We demonstrate that in acute lymphoid leukemia cells (pro-B cells), treated with 250 μM of hydrogen peroxide (H2O2), PI-PLCβ1b conferred resistance to cell death, promoting cell cycle progression and cell proliferation. Interestingly, we found that, upon H2O2 exposure, the expression of PI-PLCβ1b affects the activity of several protein kinases, in particular it completely abolished the phosphorylation of Erk1/2 MAP kinases, down-regulated PTEN and up-regulated the phosphorylation of Akt; thereby sustaining cellular proliferation

Special Student Project: Developments under the Surface Mining Control and Reclamation Act of 1977

The Surface Mining Control and Reclamation Act of 1977 (SMCRA) is one of the most significant enactments ever to affect the coal mining industry. In pervasive fashion, it is intended to control virtually every environmental aspect of surface mining as well as all surface effects of underground coal mining. The responsibility for establishing a regulatory program to refine and implement the Act is vested in the United States Department of the Interior. However, as individual regulatory plans are submitted by the states and approved by the Secretary of the Interior, the Act provides for an assumption by the states of primary regulatory authority over mining activities conducted within their borders. As of mid-1980, no state except Texas had assumed primary regulatory authority. Proposed amendments to the SMCRA, changes and uncertainties in the model regulatory program as promulgated by the Office of Surface Mining Reclamation and Enforcement (OSM), and challenges to OSM\u27s authority to regulate certain aspects of coal mining have all contributed to the delay in the states\u27 assumption of primary regulatory authority. This Project is intended to note the significant changes and challenges to the SMCRA and to the regulations promulgated thereunder over the period beginning with the issuance of the permanent regulatory program until the present time

The Effects of Trace Mineral Inclusion Management on the Performance and Mineral Status of Newly Recwived Feeder Calves

The objective of this study was to determine the effects of trace mineral inclusion management on the performance and mineral status of newly received feeder calves. Steers from 2 pastures at a single ranch in Western South Dakota blocked into non-implanted (NI; n = 64; BW = 240 kg), May implanted (MI; n = 64; BW 252 kg;) and August implanted (AI; n = 66; BW = 248 kg;) groups, then allotted to one of two treatment groups. Treatments consisted of either: a pelleted supplement fed at a fixed amount to meet the gram / daily requirement (GDR) of Cu (as CuSO4) and Zn (as ZnSO4) of a growing steer or as a percent of the diet (PER). Liver biopsy and blood samples were collected at the initiation of the trial and again after 28 d on feed. The ADG and feed conversion (F/G) was not affected by diet treatment. Cumulative DMI tended to be greater (P \u3c 0.10) in PER diets (7.31 vs. 7.12 kg). Steers receiving PER treatments tended (P \u3c 0.11) to have less of a decrease in hepatic Zn than GDR treatments. The change in hepatic K was affected (P \u3c 0.05) by implant with AI steers having the greatest increase. These results suggest that if performance and morbidity are enhanced by feeding Cu and Zn to meet the gram daily requirement of the animal, then Cu and Zn may need to be fed at a greater level to see any differences from this practice

Ectopic Expression of Ankrd2 Affects Proliferation, Motility and Clonogenic Potential of Human Osteosarcoma Cells

Simple Summary Osteosarcoma is a rare malignancy of bone, primarily affecting children and young adults. The main objective of this study was to identify novel therapeutic targets to fight the progression of this insidious disease. To this aim, the role of Ankrd2, a stress- and mechano- sensor protein known for being mostly expressed in muscle fibers, was analyzed in the modulation of osteosarcoma progression. By subjecting human osteosarcoma cell lines expressing or silencing Ankrd2 to several functional assays, our results demonstrated that Ankrd2 is involved in the pathogenesis of this cancer. Nonetheless, due to observations obtained by other studies in other model systems, our findings also suggest that Ankrd2 might behave as a "double-faced" cancer driver gene. Ankrd2 is a protein known for being mainly expressed in muscle fibers, where it participates in the mechanical stress response. Since both myocytes and osteoblasts are mesenchymal-derived cells, we were interested in examining the role of Ankrd2 in the progression of osteosarcoma which features a mechano-stress component. Although having been identified in many tumor-derived cell lines and -tissues, no study has yet described nor hypothesized any involvement for this protein in osteosarcoma tumorigenesis. In this paper, we report that Ankrd2 is expressed in cell lines obtained from human osteosarcoma and demonstrate a contribution by this protein in the pathogenesis of this insidious disease. Ankrd2 involvement in osteosarcoma development was evaluated in clones of Saos2, U2OS, HOS and MG63 cells stably expressing Ankrd2, through the investigation of hallmark processes of cancer cells. Interestingly, we found that exogenous expression of Ankrd2 influenced cellular growth, migration and clonogenicity in a cell line-dependent manner, whereas it was able to improve the formation of 3D spheroids in three out of four cellular models and enhanced matrix metalloproteinase (MMP) activity in all tested cell lines. Conversely, downregulation of Ankrd2 expression remarkably reduced proliferation and clonogenic potential of parental cells. As a whole, our data present Ankrd2 as a novel player in osteosarcoma development, opening up new therapeutic perspectives