Linear ubiquitination at a glance

Ubiquitination (also known as ubiquitylation) is a post-translational modification that creates versatility in cell signalling and regulates a multitude of cellular processes. Its versatility lies in the capacity to form eight different inter-ubiquitin linkages through the seven lysine residues of ubiquitin and through its N-terminal methionine (M1). The latter, referred to as linear or M1 linkage, is created by the linear ubiquitin chain assembly complex (LUBAC), the only E3 ligase known to date that is capable of forming linear ubiquitin chains de novo Linear ubiquitin chains are crucial modulators of innate and adaptive immune responses, and act by regulating inflammatory and cell death signalling. In this Cell Science at a Glance article and the accompanying poster, we review the current knowledge on the role of LUBAC and linear ubiquitination in immune signalling and human physiology. We specifically focus on the role for LUBAC in signalling that is induced by the cytokine tumour necrosis factor (TNF) and its role in inflammation, gene activation and cell death. Furthermore, we highlight the roles of deubiquitinases (DUBs) that cleave M1 linkages and add an additional layer in the control of LUBAC-mediated immune signalling

The linear ubiquitin chain assembly complex regulates TRAIL-induced gene activation and cell death.

The linear ubiquitin chain assembly complex (LUBAC) is the only known E3 ubiquitin ligase which catalyses the generation of linear ubiquitin linkages de novo LUBAC is a crucial component of various immune receptor signalling pathways. Here, we show that LUBAC forms part of the TRAIL-R-associated complex I as well as of the cytoplasmic TRAIL-induced complex II In both of these complexes, HOIP limits caspase-8 activity and, consequently, apoptosis whilst being itself cleaved in a caspase-8-dependent manner. Yet, by limiting the formation of a RIPK1/RIPK3/MLKL-containing complex, LUBAC also restricts TRAIL-induced necroptosis. We identify RIPK1 and caspase-8 as linearly ubiquitinated targets of LUBAC following TRAIL stimulation. Contrary to its role in preventing TRAIL-induced RIPK1-independent apoptosis, HOIP presence, but not its activity, is required for preventing necroptosis. By promoting recruitment of the IKK complex to complex I, LUBAC also promotes TRAIL-induced activation of NF-κB and, consequently, the production of cytokines, downstream of FADD, caspase-8 and cIAP1/2. Hence, LUBAC controls the TRAIL signalling outcome from complex I and II, two platforms which both trigger cell death and gene activation

f [N pi N]: from quarks to the pion derivative coupling

We study the N pi N coupling, in the framework of a QCD-inspired confining Nambu-Jona-Lasinio model. A simple relativistic confining and instantaneous quark model is reviewed. The Salpeter equation for the nucleon and the boosted pion is solved. The f [n pi n] and f[n pi Delta] couplings are calculated and they turn out to be reasonably good. The sensibility of f[n pi n] and f[n pi Delta] to confinement, chiral symmetry breaking and Lorentz invariance is briefly discussed.Comment: 30 pages in LaTex RevTex, 6 postscript figure

Investigating the Applicability in Emergency Situations of Terra Preta Sanitation System using Lactic Acid Bacteria

LAB failed to keep lacto-fermented sludge’s pH (6.7) and TAN (11.8mg/l) below 4.2 and within 15-30 mg/l respectively. This is despite registering promising results in pH (9.6) and TAN (16.6mg/l) for urine. The results challenged on-site LAB procedure in terms of stabilizing and sanitising faecal sludge possibly due to differences in sludge age, charcoal addition and different environmental factors. Therefore TPS combined with LAB inoculation could not be the best sanitation option for an immediate phase but rather second and third stages of emergency situations.  Malawi experiences emergency situations whose response does not prioritize faecal sludge management challenges. This research adopted a redefined Terra Preta Sanitation (TPS) system that replaced vermicomposting with Lactic Acid Bacteria (LAB) inoculation. The research aimed at determining possibility of on-site LAB procedure upscalling and safe separation of urine and lacto-fermented sludge as useful agricultural by-products. The study site was Crown Ministries, Blantyre, Malawi. A fermented mixture of15L pasteurized milk, 30ml of Yakult and 1.5g cane molasses was added to a 200L faecal sludge collection drum before use. After defecation, 100cm3 charcoal and 2g molasses were added. Urine was anaerobically collected in 50L drum. Random grab samples results indicated that COD for urine (868.4mg/l) and Lacto-fermented sludge (431.2mg/l) were above 60mg/l Malawi Standard and E. coli (1.05 x107) and Total coliforms (2.18 x 107) for Lacto-Fermented Sludge went above <103 CFU/100ml.

Definitiestudie afwegingskader : naar een klimaatbestendig Nederland : definitiestudie Fase 1, kaders voor afweging

Onzekerheid over (omvang en tempo van) de gevolgen van klimaatverandering vormt een essentieel punt bij beslissingen over de ruimtelijke inrichting. De mate waarin en de snelheid waarmee veranderingen optreden zijn niet precies bekend. Een afwegingskader geeft de overheid en de planontwikkelaar instrumenten in handen om de risico’s, de kansen, de kosten en de baten van klimaatadaptatie op verschillende onderscheiden thema’s inzichtelijk te maken. Afwegen: hoe doe je dat. Daarvoor wordt in drie stappen een kader voor gegeven