Linking green militarization and critical military studies

The precipitous increase in commercial poaching across parts of Africa has been met by progressively more militarized responses. Amounting to green militarization, we now see national armies, increasingly paramilitarized rangers, military tactics, and even sophisticated military technology used to address the problem. Scholarly investigations on the topic have largely been approached from a political ecology perspective and hence have not made connections with the equally relevant field of critical military studies (CMS). We see this as a missed opportunity. This paper is thus an early attempt to begin forging these connections. At the most general level, we introduce green militarization – as a practice and realm of scholarly debate – into CMS. By bringing in environmental conservation and non-human nature, this offers a broader view into the vast areas of nominally civilian life that are increasingly militarized, a defining interest of CMS. Second, we draw from core CMS insights – especially regarding the link between development and security – to grasp changing practices and trends in green militarization. In particular, we illustrate how the recent shift towards softer militarized approaches amounts to poaching-related soft counter-insurgency, which we capture in the concept of the conservation–security–development nexus. Here, communities become the object of development interventions to ‘win hearts and minds’ and prevent their involvement in poaching, thereby neutralizing the security threats poaching might pose. We close by suggesting future areas of intersection between CMS and the political-ecological work on green militarization in hopes of inciting a deeper engagement

The map-1 Gene Family in Root-Knot Nematodes, Meloidogyne spp.: A Set of Taxonomically Restricted Genes Specific to Clonal Species

Taxonomically restricted genes (TRGs), i.e., genes that are restricted to a limited subset of phylogenetically related organisms, may be important in adaptation. In parasitic organisms, TRG-encoded proteins are possible determinants of the specificity of host-parasite interactions. In the root-knot nematode (RKN) Meloidogyne incognita, the map-1 gene family encodes expansin-like proteins that are secreted into plant tissues during parasitism, thought to act as effectors to promote successful root infection. MAP-1 proteins exhibit a modular architecture, with variable number and arrangement of 58 and 13-aa domains in their central part. Here, we address the evolutionary origins of this gene family using a combination of bioinformatics and molecular biology approaches. Map-1 genes were solely identified in one single member of the phylum Nematoda, i.e., the genus Meloidogyne, and not detected in any other nematode, thus indicating that the map-1 gene family is indeed a TRG family. A phylogenetic analysis of the distribution of map-1 genes in RKNs further showed that these genes are specifically present in species that reproduce by mitotic parthenogenesis, with the exception of M. floridensis, and could not be detected in RKNs reproducing by either meiotic parthenogenesis or amphimixis. These results highlight the divergence between mitotic and meiotic RKN species as a critical transition in the evolutionary history of these parasites. Analysis of the sequence conservation and organization of repeated domains in map-1 genes suggests that gene duplication(s) together with domain loss/duplication have contributed to the evolution of the map-1 family, and that some strong selection mechanism may be acting upon these genes to maintain their functional role(s) in the specificity of the plant-RKN interactions

Soil resource supply influences faunal size–specific distributions in natural food webs

The large range of body-mass values of soil organisms provides a tool to assess the ecological organization of soil communities. The goal of this paper is to identify graphical and quantitative indicators of soil community composition and ecosystem functioning, and to illustrate their application to real soil food webs. The relationships between log-transformed mass and abundance of soil organisms in 20 Dutch meadows and heathlands were investigated. Using principles of allometry, maximal use can be made of ecological theory to build and explain food webs. The aggregate contribution of small invertebrates such as nematodes to the entire community is high under low soil phosphorus content and causes shifts in the mass–abundance relationships and in the trophic structures. We show for the first time that the average of the trophic link lengths is a reliable predictor for assessing soil fertility responses. Ordered trophic link pairs suggest a self-organizing structure of food webs according to resource availability and can predict environmental shifts in ecologically meaningful ways

Human Cord Blood Stem Cell-Modulated Regulatory T Lymphocytes Reverse the Autoimmune-Caused Type 1 Diabetes in Nonobese Diabetic (NOD) Mice

Background: The deficit of pancreatic islet b cells caused by autoimmune destruction is a crucial issue in type 1 diabetes (T1D). It is essential to fundamentally control the autoimmunity for treatment of T1D. Regulatory T cells (Tregs) play a pivotal role in maintaining self-tolerance through their inhibitory impact on autoreactive effector T cells. An abnormality of Tregs is associated with initiation of progression of T1D. Methodology/Principal Findings: Here, we report that treatment of established autoimmune-caused diabetes in NOD mice with purified autologous CD4 + CD62L + Tregs co-cultured with human cord blood stem cells (CB-SC) can eliminate hyperglycemia, promote islet b-cell regeneration to increase b-cell mass and insulin production, and reconstitute islet architecture. Correspondingly, treatment with CB-SC-modulated CD4 + CD62L + Tregs (mCD4CD62L Tregs) resulted in a marked reduction of insulitis, restored Th1/Th2 cytokine balance in blood, and induced apoptosis of infiltrated leukocytes in pancreatic islets. Conclusions/Significance: These data demonstrate that treatment with mCD4CD62L Tregs can reverse overt diabetes

ETS1 Mediates MEK1/2-Dependent Overexpression of Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A) in Human Cancer Cells

EGFR-MEK-ERK signaling pathway has an established role in promoting malignant growth and disease progression in human cancers. Therefore identification of transcriptional targets mediating the oncogenic effects of the EGFR-MEK-ERK pathway would be highly relevant. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently characterized human oncoprotein. CIP2A promotes malignant cell growth and is over expressed at high frequency (40–80%) in most of the human cancer types. However, the mechanisms inducing its expression in cancer still remain largely unexplored. Here we present systematic analysis of contribution of potential gene regulatory mechanisms for high CIP2A expression in cancer. Our data shows that evolutionary conserved CpG islands at the proximal CIP2A promoter are not methylated both in normal and cancer cells. Furthermore, sequencing of the active CIP2A promoter region from altogether seven normal and malignant cell types did not reveal any sequence alterations that would increase CIP2A expression specifically in cancer cells. However, treatment of cancer cells with various signaling pathway inhibitors revealed that CIP2A mRNA expression was sensitive to inhibition of EGFR activity as well as inhibition or activation of MEK-ERK pathway. Moreover, MEK1/2-specific siRNAs decreased CIP2A protein expression. Series of CIP2A promoter-luciferase constructs were created to identify proximal −27 to −107 promoter region responsible for MEK-dependent stimulation of CIP2A expression. Additional mutagenesis and chromatin immunoprecipitation experiments revealed ETS1 as the transcription factor mediating stimulation of CIP2A expression through EGFR-MEK pathway. Thus, ETS1 is probably mediating high CIP2A expression in human cancers with increased EGFR-MEK1/2-ERK pathway activity. These results also suggest that in addition to its established role in invasion and angiogenesis, ETS1 may support malignant cellular growth via regulation of CIP2A expression and protein phosphatase 2A inhibition

Directed Evolution Generates a Novel Oncolytic Virus for the Treatment of Colon Cancer

Background Viral-mediated oncolysis is a novel cancer therapeutic approach with the potential to be more effective and less toxic than current therapies due to the agents selective growth and amplification in tumor cells. To date, these agents have been highly safe in patients but have generally fallen short of their expected therapeutic value as monotherapies. Consequently, new approaches to generating highly potent oncolytic viruses are needed. To address this need, we developed a new method that we term “Directed Evolution” for creating highly potent oncolytic viruses. Methodology/Principal Findings Taking the “Directed Evolution” approach, viral diversity was increased by pooling an array of serotypes, then passaging the pools under conditions that invite recombination between serotypes. These highly diverse viral pools were then placed under stringent directed selection to generate and identify highly potent agents. ColoAd1, a complex Ad3/Ad11p chimeric virus, was the initial oncolytic virus derived by this novel methodology. ColoAd1, the first described non-Ad5-based oncolytic Ad, is 2–3 logs more potent and selective than the parent serotypes or the most clinically advanced oncolytic Ad, ONYX-015, in vitro. ColoAd1's efficacy was further tested in vivo in a colon cancer liver metastasis xenograft model following intravenous injection and its ex vivo selectivity was demonstrated on surgically-derived human colorectal tumor tissues. Lastly, we demonstrated the ability to arm ColoAd1 with an exogenous gene establishing the potential to impact the treatment of cancer on multiple levels from a single agent. Conclusions/Significance Using the “Directed Evolution” methodology, we have generated ColoAd1, a novel chimeric oncolytic virus. In vitro, this virus demonstrated a >2 log increase in both potency and selectivity when compared to ONYX-015 on colon cancer cells. These results were further supported by in vivo and ex vivo studies. Furthermore, these results have validated this methodology as a new general approach for deriving clinically-relevant, highly potent anti-cancer virotherapies

Low-Load High Volume Resistance Exercise Stimulates Muscle Protein Synthesis More Than High-Load Low Volume Resistance Exercise in Young Men

BACKGROUND: We aimed to determine the effect of resistance exercise intensity (%1 repetition maximum-1RM) and volume on muscle protein synthesis, anabolic signaling, and myogenic gene expression. METHODOLOGY/PRINCIPAL FINDINGS: Fifteen men (21+/-1 years; BMI=24.1+/-0.8 kg/m2) performed 4 sets of unilateral leg extension exercise at different exercise loads and/or volumes: 90% of repetition maximum (1RM) until volitional failure (90FAIL), 30% 1RM work-matched to 90%FAIL (30WM), or 30% 1RM performed until volitional failure (30FAIL). Infusion of [ring-13C6] phenylalanine with biopsies was used to measure rates of mixed (MIX), myofibrillar (MYO), and sarcoplasmic (SARC) protein synthesis at rest, and 4 h and 24 h after exercise. Exercise at 30WM induced a significant increase above rest in MIX (121%) and MYO (87%) protein synthesis at 4 h post-exercise and but at 24 h in the MIX only. The increase in the rate of protein synthesis in MIX and MYO at 4 h post-exercise with 90FAIL and 30FAIL was greater than 30WM, with no difference between these conditions; however, MYO remained elevated (199%) above rest at 24 h only in 30FAIL. There was a significant increase in AktSer473 at 24h in all conditions (P=0.023) and mTORSer2448 phosphorylation at 4 h post-exercise (P=0.025). Phosporylation of Erk1/2Tyr202/204, p70S6KThr389, and 4E-BP1Thr37/46 increased significantly (P<0.05) only in the 30FAIL condition at 4 h post-exercise, whereas, 4E-BP1Thr37/46 phosphorylation was greater 24 h after exercise than at rest in both 90FAIL (237%) and 30FAIL (312%) conditions. Pax7 mRNA expression increased at 24 h post-exercise (P=0.02) regardless of condition. The mRNA expression of MyoD and myogenin were consistently elevated in the 30FAIL condition. CONCLUSIONS/SIGNIFICANCE: These results suggest that low-load high volume resistance exercise is more effective in inducing acute muscle anabolism than high-load low volume or work matched resistance exercise modes

DUX4c Is Up-Regulated in FSHD. It Induces the MYF5 Protein and Human Myoblast Proliferation

Facioscapulohumeral muscular dystrophy (FSHD) is a dominant disease linked to contractions of the D4Z4 repeat array in 4q35. We have previously identified a double homeobox gene (DUX4) within each D4Z4 unit that encodes a transcription factor expressed in FSHD but not control myoblasts. DUX4 and its target genes contribute to the global dysregulation of gene expression observed in FSHD. We have now characterized the homologous DUX4c gene mapped 42 kb centromeric of the D4Z4 repeat array. It encodes a 47-kDa protein with a double homeodomain identical to DUX4 but divergent in the carboxyl-terminal region. DUX4c was detected in primary myoblast extracts by Western blot with a specific antiserum, and was induced upon differentiation. The protein was increased about 2-fold in FSHD versus control myotubes but reached 2-10-fold induction in FSHD muscle biopsies. We have shown by Western blot and by a DNA-binding assay that DUX4c over-expression induced the MYF5 myogenic regulator and its DNA-binding activity. DUX4c might stabilize the MYF5 protein as we detected their interaction by co-immunoprecipitation. In keeping with the known role of Myf5 in myoblast accumulation during mouse muscle regeneration DUX4c over-expression activated proliferation of human primary myoblasts and inhibited their differentiation. Altogether, these results suggested that DUX4c could be involved in muscle regeneration and that changes in its expression could contribute to the FSHD pathology