Aligning the Principles of Permaculture Design with Sustainable Open Access Practice

Open Access has seen increased acceptance in recent years, yet academic libraries continue to struggle with supporting and growing the Open Access institutional repositories (IRs) and increasing faculty awareness of and buy-in for Open Access and related scholarly communication issues. In this presentation, we propose a reframing of Open Access and scholarly communication strategies using the twelve principles of permaculture, an environmental design theory that provides a sustainable architecture for self-maintained agricultural systems modeled from naturally occurring ecosystems (Hemenway, 2009). Such an approach is beneficial for many reasons. Permaculture emphasizes maximum benefit from minimum effort and resources, which resonates with libraries that face increased strain on budgets and personnel. Further, the theory encourages that waste of resources and efforts be eliminated completely, which can guide libraries as they move towards maximizing efficiency in a changing academic culture. Permaculture also stresses that practitioners respect the diversity of the smaller ecosystems that make up the bigger picture, a principle which OA advocates and humanists are now advocating. We will share these insights and other such distillations of the permaculture design principles and offer our map to how they can be applied to Open Access and scholarly communication endeavors as we continue to make our path toward sustainable dissemination and preservation practices of today’s research output. Hemenway, T. (2009). Gaia\u27s Garden: A Guide to Home-Scale Permaculture. Chelsea Green Publishing. p. 5

Akt-Induced Phosphorylation of N-CoR at Serine 1450 Contributes to Its Misfolded Conformational Dependent Loss (MCDL) in Acute Myeloid Leukemia of the M5 Subtype

10.1371/journal.pone.0070891PLoS ONE88-POLN

A portable shield for a neutron howitzer used for instructional and research purposes

The article of record as published may be found at http://dx.doi.org/10.1016/j.apradiso.2015.05.011Neutron howitzers are routinely used in universities to activate samples for instructional laboratory experiments on radioactivity. They are also a convenient source of neutrons and gammas for research purposes, but they must be used with caution. This paper describes the modeling, design, construction, and testing of a portable, economical shield for a 1.0 Curie neutron howitzer. The Monte Carlo N Particle Transport Code (MCNP5) has been used to model the 239PuBe source and the howitzer and to design the external neutron and gamma shield

Molecular Biomarkers of Vascular Dysfunction in Obstructive Sleep Apnea

Untreated and long-lasting obstructive sleep apnea (OSA) may lead to important vascular abnormalities, including endothelial cell (EC) dysfunction, hypertension, and atherosclerosis. We observed a correlation between microcirculatory reactivity and endothelium-dependent release of nitric oxide in OSA patients. Therefore, we hypothesized that OSA affects (micro)vasculature and we aimed to identify vascular gene targets of OSA that could possibly serve as reliable biomarkers of severity of the disease and possibly of vascular risk. Using quantitative RT-PCR, we evaluated gene expression in skin biopsies of OSA patients, mouse aortas from animals exposed to 4-week intermittent hypoxia (IH; rapid oscillations in oxygen desaturation and reoxygenation), and human dermal microvascular (HMVEC) and coronary artery endothelial cells (HCAEC) cultured under IH. We demonstrate a significant upregulation of endothelial nitric oxide synthase (eNOS), tumor necrosis factor-alpha-induced protein 3 (TNFAIP3; A20), hypoxia-inducible factor 1 alpha (HIF-1α?? and vascular endothelial growth factor (VEGF) expression in skin biopsies obtained from OSA patients with severe nocturnal hypoxemia (nadir saturated oxygen levels [SaO2]<75%) compared to mildly hypoxemic OSA patients (SaO2 75%–90%) and a significant upregulation of vascular cell adhesion molecule 1 (VCAM-1) expression compared to control subjects. Gene expression profile in aortas of mice exposed to IH demonstrated a significant upregulation of eNOS and VEGF. In an in vitro model of OSA, IH increased expression of A20 and decreased eNOS and HIF-1α expression in HMVEC, while increased A20, VCAM-1 and HIF-1αexpression in HCAEC, indicating that EC in culture originating from distinct vascular beds respond differently to IH stress. We conclude that gene expression profiles in skin of OSA patients may correlate with disease severity and, if validated by further studies, could possibly predict vascular risk in OSA patients

Intraoperative Vertebral Artery Angiography to Guide C1-2 Transarticular Screw Fixation in a Patient with Athetoid Cerebral Palsy

We present a case of an athetoid cerebral palsy with quadriparesis caused by kyphotic deformity of the cervical spine, severe spinal stenosis at the cervicomedullary junction, and atlantoaxial instability. The patient improved after the first surgery, which included a C1 total laminectomy and C-arm guided righ side unilateral C1-2 transarticular screw fixation. C1-2 fixation was not performed on the other side because of an aberrant and dominant vertebral artery (VA). Eight months after the first operation, the patient required revision surgery for persistent neck pain and screw malposition. We used intraoperative VA angiography with simultaneous fluoroscopy for precise image guidance during bilateral C1-2 transarticular screw fixation. Intraoperative VA angiography allowed the accurate insertion of screws, and can therefore be used to avoid VA injury during C1-2 transarticular screw fixation in comorbid patients with atlantoaxial deformities

Equine Herpesvirus Protein E10 Induces Membrane Recruitment and Phosphorylation of Its Cellular Homologue, Bcl-10

v-E10, a caspase recruitment domain (CARD)-containing gene product of equine herpesvirus 2, is the viral homologue of the bcl-10 protein whose gene was found to be translocated in mucosa-associated lymphoid tissue (MALT) lymphomas. v-E10 efficiently activates the c-jun NH2-terminal kinase (JNK), p38 stress kinase, and the nuclear factor (NF)-κB transcriptional pathway and interacts with its cellular homologue, bcl-10, via a CARD-mediated interaction. Here we demonstrate that v-E10 contains a COOH-terminal geranylgeranylation consensus site which is responsible for its plasma membrane localization. Expression of v-E10 induces hyperphosphorylation and redistribution of bcl-10 from the cytoplasm to the plasma membrane, a process which is dependent on the intactness of the v-E10 CARD motif. Both membrane localization and a functional CARD motif are important for v-E10–mediated NF-κB induction, but not for JNK activation, which instead requires a functional v-E10 binding site for tumor necrosis factor receptor–associated factor (TRAF)6. Moreover, v-E10–induced NF-κB activation is inhibited by a dominant negative version of the bcl-10 binding protein TRAF1, suggesting that v-E10–induced membrane recruitment of cellular bcl-10 induces constitutive TRAF-mediated NF-κB activation

Role of Chaperone Mediated Autophagy (CMA) in the Degradation of Misfolded N-CoR Protein in Non-Small Cell Lung Cancer (NSCLC) Cells

Nuclear receptor co-repressor (N-CoR) plays important role in transcriptional control mediated by several tumor suppressor proteins. Recently, we reported a role of misfolded-conformation dependent loss (MCDL) of N-CoR in the activation of oncogenic survival pathway in acute promyelocytic leukemia (APL). Since N-CoR plays important role in cellular homeostasis in various tissues, therefore, we hypothesized that an APL like MCDL of N-CoR might also be involved in other malignancy. Indeed, our initial screening of N-CoR status in various leukemia and solid tumor cells revealed an APL like MCDL of N-CoR in primary and secondary tumor cells derived from non-small cell lung cancer (NSCLC). The NSCLC cell specific N-CoR loss could be blocked by Kaletra, a clinical grade protease inhibitor and by genistein, an inhibitor of N-CoR misfolding previously characterized by us. The misfolded N-CoR presented in NSCLC cells was linked to the amplification of ER stress and was subjected to degradation by NSCLC cell specific aberrant protease activity. In NSCLC cells, misfolded N-CoR was found to be associated with Hsc70, a molecular chaperone involved in chaperone mediated autophagy (CMA). Genetic and chemical inhibition of Lamp2A, a rate limiting factor of CMA, significantly blocked the loss of N-CoR in NSCLC cells, suggesting a crucial role of CMA in N-CoR degradation. These findings identify an important role of CMA-induced degradation of misfolded N-CoR in the neutralization of ER stress and suggest a possible role of misfolded N-CoR protein in the activation of oncogenic survival pathway in NSCLC cells

Role of Misfolded N-CoR Mediated Transcriptional Deregulation of Flt3 in Acute Monocytic Leukemia (AML)-M5 Subtype

The nuclear receptor co-repressor (N-CoR) is a key component of the generic multi-protein complex involved in transcriptional control. Flt3, a key regulator of hematopoietic cell growth, is frequently deregulated in AML (acute myeloid leukemia). Here, we report that loss of N-CoR-mediated transcriptional control of Flt3 due to misfolding, contributes to malignant growth in AML of the M5 subtype (AML-M5). An analysis of hematopoietic genes in AML cells led to the identification of Flt3 as a transcriptional target of N-CoR. Flt3 level was inversely related to N-CoR status in various leukemia cells. N-CoR was associated with the Flt3 promoter in-vivo, and a reporter driven by the Flt3 promoter was effectively repressed by N-CoR. Blocking N-CoR loss with Genistein; an inhibitor of N-CoR misfolding, significantly down-regulated Flt3 levels regardless of the Flt3 receptor mutational status and promoted the differentiation of AML-M5 cells. While stimulation of the Flt3 receptor with the Flt3 ligand triggered N-CoR loss, Flt3 antibody mediated blockade of Flt3 ligand-receptor binding led to N-CoR stabilization. Genetic ablation of N-CoR potentiated Flt3 ligand induced proliferation of BA/F3 cells. These findings suggest that N-CoR-induced repression of Flt3 might be crucial for limiting the contribution of the Flt3 signaling pathway on the growth potential of leukemic cells and its deregulation due to N-CoR loss in AML-M5, could contribute to malignant growth by conferring a proliferative advantage to the leukemic blasts. Therapeutic restoration of N-CoR function could thus be a useful approach in restricting the contribution of the Flt3 signaling pathway in AML-M5 pathogenesis