Military business and the business of the military

Contrary to dominant approaches that locate the causes for military entrepreneurialism in eastern Democratic Republic of the Congo predominantly in criminal military elites, this article highlights the importance of the Congolese military’s (FARDC) civilian context for understanding military revenue-generation. It analyses how the latter is shaped by structures of domination, signification and legitimisation that drive and are driven by the FARDC’s governance, private protection and security practices. It argues that these practices contribute to bestowing a degree of legitimacy on both the FARDC’s position of power and some of its revenue-generation activities. Furthermore, by emphasising that the FARDC’s regulatory and protection practices are partly the product of popular demands and the routine actions of civilians, the article contends that the causes of military revenue-generation are co-located in the military’s civilian environment. In this manner, it offers a more nuanced conceptualisation of military entrepreneurialism, thus opening up new perspectives on policy interventions in this area

Coordinated Translocation of Mammalian Gli Proteins and Suppressor of Fused to the Primary Cilium

Intracellular transduction of Hedgehog (Hh) signals in mammals requires functional primary cilia. The Hh signaling effectors, the Gli family of transcription factors, and their negative regulator, Suppressor of Fused (Sufu), accumulate at the tips of cilia; however, the molecular mechanism regulating this localization remains elusive. In the current study, we show that the ciliary localization of mammalian Gli proteins depends on both their N-terminal domains and a central region lying C-terminal to the zinc-finger DNA-binding domains. Invertebrate Gli homologs Ci and Tra1, when over-expressed in ciliated mouse fibroblasts, fail to localize to the cilia, suggesting the lack of a vertebrate-specific structural feature required for ciliary localization. We further show that activation of protein kinase A (PKA) efficiently inhibits ciliary localization of Gli2 and Gli3, but only moderately affects the ciliary localization of Gli1. Interestingly, variants of Gli2 mimicking the phosphorylated or non-phosphorylated states of Gli2 are both localized to the cilia, and their ciliary localizations are subjected to the inhibitory effect of PKA activation, suggesting a likely indirect mechanism underlying the roles of PKA in Gli ciliary localization. Finally, we show that ciliary localization of Sufu is dependent on ciliary-localized Gli proteins, and is inhibited by PKA activation, suggesting a coordinated mechanism for the ciliary translocation of Sufu and Gli proteins

SUMOylation by Pias1 Regulates the Activity of the Hedgehog Dependent Gli Transcription Factors

Hedgehog (Hh) signaling, a vital signaling pathway for the development and homeostasis of vertebrate tissues, is mediated by members of the Gli family of zinc finger transcription factors. Hh signaling increases the transcriptional activity of Gli proteins, at least in part, by inhibiting their proteolytic processing. Conversely, phosphorylation by cAMP-dependent protein kinase (PKA) inhibits Gli transcriptional activity by promoting their ubiquitination and proteolysis. Whether other post-translational modifications contribute to the regulation of Gli protein activity has been unclear.Here we provide evidence that all three Gli proteins are targets of small ubiquitin-related modifier (SUMO)-1 conjugation. Expression of SUMO-1 or the SUMO E3 ligase, Pias1, increased Gli transcriptional activity in cultured cells. Moreover, PKA activity reduced Gli protein SUMOylation. Strikingly, in the embryonic neural tube, the forced expression of Pias1 increased Gli activity and induced the ectopic expression of the Gli dependent gene Nkx2.2. Conversely, a point mutant of Pias1, that lacks ligase activity, blocked the endogenous expression of Nkx2.2.Together, these findings provide evidence that Pias1-dependent SUMOylation influences Gli protein activity and thereby identifies SUMOylation as a post-translational mechanism that regulates the hedgehog signaling pathway

Mouse hitchhiker mutants have spina bifida, dorso-ventral patterning defects and polydactyly: identification of Tulp3 as a novel negative regulator of the Sonic hedgehog pathway

The mammalian Sonic hedgehog (Shh) signalling pathway is essential for embryonic development and the patterning of multiple organs. Disruption or activation of Shh signalling leads to multiple birth defects, including holoprosencephaly, neural tube defects and polydactyly, and in adults results in tumours of the skin or central nervous system. Genetic approaches with model organisms continue to identify novel components of the pathway, including key molecules that function as positive or negative regulators of Shh signalling. Data presented here define Tulp3 as a novel negative regulator of the Shh pathway. We have identified a new mouse mutant that is a strongly hypomorphic allele of Tulp3 and which exhibits expansion of ventral markers in the caudal spinal cord, as well as neural tube defects and preaxial polydactyly, consistent with increased Shh signalling. We demonstrate that Tulp3 acts genetically downstream of Shh and Smoothened (Smo) in neural tube patterning and exhibits a genetic interaction with Gli3 in limb development. We show that Tulp3 does not appear to alter expression or processing of Gli3, and we demonstrate that transcriptional regulation of other negative regulators (Rab23, Fkbp8, Thm1, Sufu and PKA) is not affected. We discuss the possible mechanism of action of Tulp3 in Shh-mediated signalling in light of these new data

Role of endometriosis fertility index system in predicting non-IVF conception in patients with surgically documented endometriosis

Background: Endometriosis still remains an enigmatic disease. There are important reasons to stage endometriosis and to prognosticate the chances of pregnancy after a surgical management. The currently used revised AFS system has poor correlation with pregnancy rate. A scoring system-Endometriosis fertility index (EFI) to prognosticate the outcome was proposed few years back. The objective was to assess the usefulness of the EFI system in predicting pregnancy in patients with surgically documented endometriosis who attempt Non-IVF conception.Methods: Retrospective data was collected from 77 subjects with endometriosis who underwent laparoscopy and had documented least function (LF) score and EFI score. All were followed up until 12 months for the occurrence of a non IVF pregnancy.Results: Our study showed that the pregnancy rate was clearly higher in those with high EFI scores than those with low scores. A score of less than 4 was associated with significantly lower pregnancy rates than those with score above 5 (n=26, pregnancy rate- 11.54%) vs. (n=51, pregnancy rate 50.1%); p = 0.001)). Similarly, the pregnancy rate was significantly lower in those with LF score 1-3 (21.2%) as opposed to those with higher LF scores (p =0.029). Also, sensitivity analysis showed that higher EFI score was significantly associated with higher LF score (P <0.001).Conclusions: EFI is a useful clinical tool that predicts pregnancy with reasonable accuracy after endometriosis surgery. Its use clearly provides reassurance to those patients with good prognosis

Anti-mullerian hormone and antral follicle count as predictors of ovarian response in assisted reproduction

Objective: The objective of this study was to test the hypothesis that AMH and antral follicle count (AFC) are good predictors of ovarian response to controlled ovarian stimulation and to compare them. Materials and Methods: This observational cross-sectional study included 56 subjects aged between 25 and 42 years who were enrolled between 1 st January and 31 st December 2010 for their first intracytoplasmic sperm injection (ICSI) program. Baseline hormone profiles including serum levels of Estradiol (E2), Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), and Anti-mullerian Hormone (AMH) were determined on day 3 of the previous cycle. The antral follicle count measurements were performed on days 3-5 of the same menstrual cycle. Antral follicles within the bilateral ovaries between 2-6 mm were recorded. The subjects were treated with long protocol for ovarian stimulation. Ovulation was induced with 10,000 IU of human chorionic gonadotropin (hCG) when at least 3 follicles attained the size of more than 17 mm. Transvaginal oocyte retrieval was performed under ultrasound guidance 36 hours after hCG administration. An oocyte count less than 4 and absence of follicular growth with controlled ovarian hyper stimulation was considered as poor ovarian response. Oocyte count of 4 or more was considered as normal ovarian response. Results: Statistical analysis was performed using SPSS software trail version 16.0. Subjects were divided into 2 groups, depending on the ovarian response. The mean oocyte counts were 12.27 ± 6.06 and 2.22 ± 1.24 in normal and poor responders, respectively, ( P = 001). Multiple regression analysis revealed AMH and antral follicle count as predictors of ovarian response (β coefficient ± SE for AMH was 1.618 ± 0.602 ( P = 0.01) and for AFC, it was, 0.528 ± 0.175 ( P = 0.004). AFC was found to be a better predictor of ovarian response compared to AMH in controlled ovarian hyper stimulation. Conclusion: The observations made in this study revealed that both AMH and AFC are good predictors of ovarian response; AFC being a better predictor compared to AMH

Microbiologic epidemiology depending on time to occurrence of prosthetic joint infection: a prospective cohort study

Objectives: The high microbiologic diversity encountered in prosthetic joint infection (PJI) makes the choice of empirical antimicrobial therapies challenging, especially in cases of implant retention or one-stage exchange. Despite the risk of dysbiosis and toxicity, the combination of vancomycin with a broad-spectrum β-lactam is currently recommended in all cases, even if Gram-negative bacilli (GNB) might be less represented in late PJI. In this context, this study aimed to describe the microbiologic epidemiology of PJI according to the chronology of infection. Methods: This prospective cohort study (2011–2016) evaluated the microbiologic aetiology of 567 PJI according to time of occurrence from prosthesis implantation—early (<3 months), delayed (3–12 months) and late (>12 months)—as well as mechanism of acquisition. Results: Initial microbiologic documentation (n = 511; 90.1%) disclosed 164 (28.9%) Staphylococcus aureus (including 26 (16.1%) methicillin-resistant S. aureus), 162 (28.6%) coagulase-negative staphylococci (including 81 (59.1%) methicillin-resistant coagulase-negative staphylococci), 80 (14.1%) Enterobacteriaceae, 74 (13.1%) streptococci and 60 (10.6%) Cutibacterium acnes. Considering nonhaematogenous late PJI (n = 182), Enterobacteriaceae (n = 7; 3.8%) were less represented than in the first year after implantation (n = 56; 17.2%; p <0.001), without difference regarding nonfermenting GNB (4.6% and 2.7%, respectively). The prevalence of anaerobes (n = 40; 21.9%; including 32 (80.0%) C. acnes) was higher in late PJI (p <0.001). Consequently, a broad-spectrum β-lactam might be useful in 12 patients (6.6%) with late PJI only compared to 66 patients (20.3%) with early/delayed PJI (p <0.001). Conclusions: Considering the minority amount of GNB in late postoperative PJI, the empirical use of a broad-spectrum β-lactam should be reconsidered, especially when a two-stage exchange is planned