Heparanase-2 protects from LPS-mediated endothelial injury by inhibiting TLR4 signalling

The endothelial glycocalyx and its regulated shedding are important to vascular health. Endo-β-D-glucuronidase heparanase-1 (HPSE1) is the only enzyme that can shed heparan sulfate. However, the mechanisms are not well understood. We show that HPSE1 activity aggravated Toll-like receptor 4 (TLR4)-mediated response of endothelial cells to LPS. On the contrary, overexpression of its endogenous inhibitor, heparanase-2 (HPSE2) was protective. The microfluidic chip flow model confirmed that HPSE2 prevented heparan sulfate shedding by HPSE1. Furthermore, heparan sulfate did not interfere with cluster of differentiation-14 (CD14)-dependent LPS binding, but instead reduced the presentation of the LPS to TLR4. HPSE2 reduced LPS-mediated TLR4 activation, subsequent cell signalling, and cytokine expression. HPSE2-overexpressing endothelial cells remained protected against LPS-mediated loss of cell-cell contacts. In vivo, expression of HPSE2 in plasma and kidney medullary capillaries was decreased in mouse sepsis model. We next applied purified HPSE2 in mice and observed decreases in TNFα and IL-6 plasma concentrations after intravenous LPS injections. Our data demonstrate the important role of heparan sulfate and the glycocalyx in endothelial cell activation and suggest a protective role of HPSE2 in microvascular inflammation. HPSE2 offers new options for protection against HPSE1-mediated endothelial damage and preventing microvascular disease. © 2019, The Author(s)

Author Correction: Heparanase-2 protects from LPS-mediated endothelial injury by inhibiting TLR4 signalling

The Acknowledgements section in the original version of this Article was incomplete. “We are grateful to Prof. Israel Vlodavsky (Technion, Haifa, Israel) for giving us 1c7 antibody to HPSE2. We are grateful to Prof. Fridrich Luft for critical editing the manuscript. Grants from German Federal Ministry of Education and Research (BMBF) Nr. 031A577A and 031A577B funded this research. This work was also supported by a grant for the German Research Council to H.H. Ha1388/17-1.” now reads: “We are grateful to Prof. Israel Vlodavsky (Technion, Haifa, Israel) for giving us 1c7 antibody to HPSE2. We are grateful to Prof. Fridrich Luft for critical editing the manuscript. Grants from German Federal Ministry of Education and Research (BMBF) Nr. 031A577A and 031A577B funded this research. This work was also supported by a grant for the German Research Council to H.H. Ha1388/17-1. This work was also supported by a grant from the Else Kröner-Fresenius-Stiftung (EKFS): Grant 2017_A96.” The original Article has been corrected

The effect of religious extremism on Nigeria National Security : an appraisal of Boko Haram

Religion plays a dominant role and serves as a driving force of human action or inaction in Nigeria. In some instances, it has been exploited to serve a motive that does not align with the proper functioning of society, what is called religious extremism. One form of such religious extremism has produced Boko Haram, whose activities have threatened Nigeria’s national security. Studies have tried to unearth the causes and impact of the sect on the national security of the country. This study contributes to that debate by evaluating the impact Boko Haram has on Nigeria’s national security, and the strategies, challenges, and solutions to address the menace. Qualitative research approach, specifically historical research methodology was used in this study to illuminate the phenomenon of Boko Haram and national security in Nigeria. Data was sourced primarily from secondary and primary data with a focus on states in Northern Nigeria between 2011-2022 years. The study found that the failure of the state to provide basic amenities, extreme poverty, illiteracy, and radicalization are the primary reasons for the rise of Boko Haram in Nigeria. The study also found that the activities of the sect has impacted the socio-economic and national security of the country. The kinetic and non-kinetic approaches are the dominant strategies employed by the government to fight Boko Haram. The major recommendation is that the Nigerian government should provide economic opportunities and infrastructural facilities to reverse poverty, promote an inclusive social development and discourage the youths from venturing into terrorism. Also, sensitization programmes must be carried out to alert for the consequences and educate the youths against joining the sect. Focus should also be on expanding the deradicalization programme to support the repentant terrorists. The government should also demonstrate the political will to end terrorism in Nigeria

Infochemical induced trait changes in Alexandrium

Induced phenotypic changes due to infochemicals present in the water column are common phenomena in the aquatic ecosystem. Such infochemicals have to be reliable for the receiver and can induce changes on several hierarchical levels of biological organization. We present a synthesis of results concerning the infochemical-based phenotypic changes within the marine ‘Red Tide’ dinoflagellate Alexandrium spp. and its sympatric copepod grazers. We show that chemical cues from copepods induce a response that is specific on several levels: 1) On the level of the grazer itself, i.e. its grazing impact, 2) on the level of the Alexandrium species receiving the infochemicals and 3) on the genotypic level. As specific as the infochemicals are the observed phenotypic changes in the respective species / genotype that comprise morphology and toxin production (Paralytic Shellfish Poisoning Toxins, PSTs). We further present metabolomic and transcriptomic changes within Alexandrium spp. that will give additional insight into trait changes uninvestigated so far and the regulation of the PST-content in this notorious Red Tide species