Assessing decentralised policy implementation in Vietnam : The case of land recovery and resettlement in the Vung Ang Economic Zone

From 2006 plans were implemented to create a deep-sea water port linked to an Economic Zone in the coastal Province of Ha Tinh, located in north central Vietnam. The multi-purpose Zone entitled ‘Vung Ang’, was to attract foreign investors, while the port would provide a link to nearby Laos and Thailand. The project obviously had large implications for the administrations at various levels of governance from Hanoi to the coastal communes and villages, but even more serious impacts on the people living in the affected areas. A large area of about 23,000 hectares was to be cleared, affecting the people of 9 communes, in some of which all inhabitants had to leave their houses and homesteads, to be relocated to completely new settlements about 10 miles inland. These tightly knit communities were not too happy with the prospect to leave their homes and land, the burial places of their ancestors, and the long term comforts of community support networks. While initial decision making process started at the highest levels of Vietnam Governance, the implementation of port and industrial park construction and the related relocation policy was delegated to Ha Tinh province, which is consistent with current decentralisation policies in Vietnam. Actual implementation was carried out by the affected District and Commune level officials – with support from the Communist Party led Mass Organisations – who were in charge of the planning and implementation of the relocation process. This entailed a complex and sensitive series of steps to inform affected households, prepare relocation areas and allocate compensation and alternative housing. This paper describes the implementation dynamics of relocation by depicting and assessing the roles of all stakeholders involved, including the impacts - for better or for worse – of the relocated households. It brings out the way local authorities dealt with affected people, including efforts linked to the ideal of grass-roots democracy. Key areas of contestation are uncovered, such as inadequate infrastructure and low compensation rates. The paper has a second objective to assess the degree to which decentralisation in Vietnam has been actually implemented, and how this affects policy making processes such as the Vung Ang port/industrial zone project. The paper concludes that the relocation policy was implemented in a fairly efficient and harmonious way – with a very intensive engagement of the entire provincial administrative machinery, but that it is too early to assess the livelihood opportunities of the relocated households

Effects of Cooling During Exercise on Thermoregulatory Responses of Men With Paraplegia.

BACKGROUND: People with spinal cord injury (SCI) have an altered afferent input to the thermoregulatory center, resulting in a reduced efferent response (vasomotor control and sweating capacity) below the level of the lesion. Consequently, core body temperature rises more rapidly during exercise in individuals with SCI compared with people who are able-bodied. Cooling strategies may reduce the thermophysiological strain in SCI. OBJECTIVE: The aim of this study was to examine the effects of a cooling vest on the core body temperature response of people with a thoracic SCI during submaximal exercise. METHODS: Ten men (mean age=44 years, SD=11) with a thoracic lesion (T4-T5 or below) participated in this randomized crossover study. Participants performed two 45-minute exercise bouts at 50% maximal workload (ambient temperature 25°C), with participants randomized to a group wearing a cooling vest or a group wearing no vest (separate days). Core body temperature and skin temperature were continuously measured, and thermal sensation was assessed every 3 minutes. RESULTS: Exercise resulted in an increased core body temperature, skin temperature, and thermal sensation, whereas cooling did not affect core body temperature. The cooling vest effectively decreased skin temperature, increased the core-to-trunk skin temperature gradient, and tended to lower thermal sensation compared with the control condition. LIMITATIONS: The lack of differences in core body temperature among conditions may be a result of the relative moderate ambient temperature in which the exercise was performed. CONCLUSIONS: Despite effectively lowering skin temperature and increasing the core-to-trunk skin temperature gradient, there was no impact of the cooling vest on the exercise-induced increase in core body temperature in men with low thoracic SCI

Platelet-activating factor (PAF) mediates NLRP3-NEK7 inflammasome induction independently of PAFR

The role of lipids in inflammasome activation remains underappreciated. The phospholipid, platelet-activating factor (PAF), exerts multiple physiological functions by binding to a G protein-coupled seven-transmembrane receptor (PAFR). PAF is associated with a number of inflammatory disorders, yet the molecular mechanism underlying its proinflammatory function remains to be fully elucidated. We show that multiple PAF isoforms and PAF-like lipids can activate the inflammasome, resulting in IL-1β and IL-18 maturation. This is dependent on NLRP3, ASC, caspase-1, and NEK7, but not on NLRC4, NLRP1, NLRP6, AIM2, caspase-11, or GSDMD. Inflammasome activation by PAF also requires potassium efflux and calcium influx but not lysosomal cathepsin or mitochondrial reactive oxygen species. PAF exacerbates peritonitis partly through inflammasome activation, but PAFR is dispensable for PAF-induced inflammasome activation in vivo or in vitro. These findings reveal that PAF represents a damage-associated signal that activates the canonical inflammasome independently of PAFR and provides an explanation for the ineffectiveness of PAFR antagonist in blocking PAF-mediated inflammation in the clinic

Viral DNA Binding to NLRC3, an Inhibitory Nucleic Acid Sensor, Unleashes STING, a Cyclic Dinucleotide Receptor that Activates Type I Interferon

Immune suppression is a crucial component of immunoregulation and a subgroup of nucleotide-binding domain (NBD), leucine-rich repeat (LRR)-containing proteins (NLRs) attenuate innate immunity. How this inhibitory function is controlled is unknown. A key question is whether microbial ligands can regulate this inhibition. NLRC3 is a negative regulator that attenuates type I interferon (IFN-I) response by sequestering and attenuating stimulator of interferon genes (STING) activation. Here, we report that NLRC3 binds viral DNA and other nucleic acids through its LRR domain. DNA binding to NLRC3 increases its ATPase activity, and ATP-binding by NLRC3 diminishes its interaction with STING, thus licensing an IFN-I response. This work uncovers a mechanism wherein viral nucleic acid binding releases an inhibitory innate receptor from its target

Sting agonist mitigates experimental autoimmune encephalomyelitis by stimulating type i ifn-dependent and -independent immune-regulatory pathways

The cGAS-cyclic GMP-AMP (cGAMP)-stimulator of IFN genes (STING) pathway induces a powerful type I IFN (IFN-I) response and is a prime candidate for augmenting immunity in cancer immunotherapy and vaccines. IFN-I also has immuneregulatory functions manifested in several autoimmune diseases and is a first-line therapy for relapsing-remitting multiple sclerosis. However, it is only moderately effective and can induce adverse effects and neutralizing Abs in recipients. Targeting cGAMP in autoimmunity is unexplored and represents a challenge because of the intracellular location of its receptor, STING. We used microparticle (MP)-encapsulated cGAMP to increase cellular delivery, achieve dose sparing, and reduce potential toxicity. In the C57BL/6 experimental allergic encephalomyelitis (EAE) model, cGAMP encapsulated in MPs (cGAMP MPs) administered therapeutically protected mice from EAE in a STING-dependent fashion, whereas soluble cGAMP was ineffective. Protection was also observed in a relapsing-remitting model. Importantly, cGAMP MPs protected against EAE at the peak of disease and were more effective than rIFN-b. Mechanistically, cGAMP MPs showed both IFN-I-dependent and -independent immunosuppressive effects. Furthermore, it induced the immunosuppressive cytokine IL-27 without requiring IFN-I. This augmented IL-10 expression through activated ERK and CREB. IL-27 and subsequent IL-10 were the most important cytokines to mitigate autoreactivity. Critically, cGAMP MPs promoted IFN-I as well as the immunoregulatory cytokines IL-27 and IL-10 in PBMCs from relapsing-remitting multiple sclerosis patients. Collectively, this study reveals a previously unappreciated immune-regulatory effect of cGAMP that can be harnessed to restrain T cell autoreactivity

TRAF3IP3 negatively regulates cytosolic RNA induced anti-viral signaling by promoting TBK1 K48 ubiquitination

Innate immunity to nucleic acids forms the backbone for anti-viral immunity and several inflammatory diseases. Upon sensing cytosolic viral RNA, retinoic acid-inducible gene-I-like receptors (RLRs) interact with the mitochondrial antiviral signaling protein (MAVS) and activate TANK-binding kinase 1 (TBK1) to induce type I interferon (IFN-I). TRAF3-interacting protein 3 (TRAF3IP3, T3JAM) is essential for T and B cell development. It is also well-expressed by myeloid cells, where its role is unknown. Here we report that TRAF3IP3 suppresses cytosolic poly(I:C), 5’ppp-dsRNA, and vesicular stomatitis virus (VSV) triggers IFN-I expression in overexpression systems and Traf3ip3−/− primary myeloid cells. The mechanism of action is through the interaction of TRAF3IP3 with endogenous TRAF3 and TBK1. This leads to the degradative K48 ubiquitination of TBK1 via its K372 residue in a DTX4-dependent fashion. Mice with myeloid-specific gene deletion of Traf3ip3 have increased RNA virus-triggered IFN-I production and reduced susceptibility to virus. These results identify a function of TRAF3IP3 in the regulation of the host response to cytosolic viral RNA in myeloid cells

Recommendations for intervertebral disc notochordal cell investigation: from isolation to characterization

Background Lineage-tracing experiments have established that the central region of the mature intervertebral disc, the nucleus pulposus (NP), develops from the embryonic structure called “the notochord”. However, changes in the cells derived from the notochord which form the NP (i.e., notochordal cells [NCs]), in terms of their phenotype and functional identity from early developmental stages to skeletal maturation are less understood. These key issues require further investigation to better comprehend the role of NCs in homeostasis and degeneration as well as their potential for regeneration. Progress in utilizing NCs is currently hampered due to poor consistency and lack of consensus methodology for in vitro NC extraction, manipulation, and characterization. Methods Here, an international group has come together to provide key recommendations and methodologies for NC isolation within key species, numeration, in vitro manipulation and culture, and characterization. Results Recommeded protocols are provided for isolation and culture of NCs. Experimental testing provided recommended methodology for numeration of NCs. The issues of cryopreservation are demonstrated, and a pannel of immunohistochemical markers are provided to inform NC characterization. Conclusions Together we hope this article provides a road map for in vitro studies of NCs to support advances in research into NC physiology and their potential in regenerative therapies

NLRP12 Regulates Anti-viral RIG-I Activation via Interaction with TRIM25

Establishing the balance between positive and negative innate immune mechanisms is crucial for maintaining homeostasis. Here we uncover the regulatory crosstalk between two previously unlinked innate immune receptor families: RIG-I, an anti-viral cytosolic receptor activated type I interferon production, and NLR (nucleotide-binding domain, leucine repeat domain-containing protein). We show that NLRP12 dampens RIG-I-mediated immune signaling against RNA viruses by controlling RIG-I's association with its adaptor MAVS. The nucleotide-binding domain of NLRP12 interacts with the ubiquitin ligase TRIM25 to prevent TRIM25-mediated, Lys63-linked ubiquitination and activation of RIG-I. NLRP12 also enhances RNF125-mediated, Lys48-linked degradative ubiquitination of RIG-I. Vesicular stomatitis virus (VSV) infection downregulates NLRP12 expression to allow RIG-I activation. Myeloid-cell-specific Nlrp12-deficient mice display a heightened interferon and TNF response and are more resistant to VSV infection. These results indicate that NLRP12 functions as a checkpoint for anti-viral RIG-I activation. Chen et al. show that the nucleotide-binding domain and leucine repeat domain-containing protein NLRP12 associates with the ubiquitin ligase TRIM25 to reduce K63-linked ubiquitination of the anti-viral innate immune receptor RIG-I. This prevents RIG-I association with MAVS and thus serves as a checkpoint for interferon and cytokine induction in response to RNA viruses

Multi-omics analyses of radiation survivors identify radioprotective microbes and metabolites

Ionizing radiation causes acute radiation syndrome, which leads to hematopoietic, gastrointestinal, and cerebrovascular injuries. We investigated a population of mice that recovered from high-dose radiation to live normal life spans. These "elite-survivors" harbored distinct gut microbiota that developed after radiation and protected against radiation-induced damage and death in both germ-free and conventionally housed recipients. Elevated abundances of members of the bacterial taxa Lachnospiraceae and Enterococcaceae were associated with postradiation restoration of hematopoiesis and gastrointestinal repair. These bacteria were also found to be more abundant in leukemia patients undergoing radiotherapy, who also displayed milder gastrointestinal dysfunction. In our study in mice, metabolomics revealed increased fecal concentrations of microbially derived propionate and tryptophan metabolites in elite-survivors. The administration of these metabolites caused long-term radioprotection, mitigation of hematopoietic and gastrointestinal syndromes, and a reduction in proinflammatory responses

Molecular systematics of the marine Dothideomycetes

Phylogenetic analyses of four nuclear genes, namely the large and small subunits of the nuclear ribosomal RNA, transcription elongation factor 1-alpha and the second largest RNA polymerase II subunit, established that the ecological group of marine bitunicate ascomycetes has representatives in the orders Capnodiales, Hysteriales, Jahnulales, Mytilinidiales, Patellariales and Pleosporales. Most of the fungi sequenced were intertidal mangrove taxa and belong to members of 12 families in the Pleosporales: Aigialaceae, Didymellaceae, Leptosphaeriaceae, Lenthitheciaceae, Lophiostomataceae, Massarinaceae, Montagnulaceae, Morosphaeriaceae, Phaeosphaeriaceae, Pleosporaceae, Testudinaceae and Trematosphaeriaceae. Two new families are described: Aigialaceae and Morosphaeriaceae, and three new genera proposed: Halomassarina, Morosphaeria and Rimora. Few marine species are reported from the Dothideomycetidae (e.g. Mycosphaerellaceae, Capnodiales), a group poorly studied at the molecular level. New marine lineages include the Testudinaceae and Manglicola guatemalensis in the Jahnulales. Significantly, most marine Dothideomycetes are intertidal tropical species with only a few from temperate regions on salt marsh plants (Spartina species and Juncus roemerianus), and rarely totally submerged (e.g. Halotthia posidoniae and Pontoporeia biturbinata on the seagrasses Posidonia oceanica and Cymodocea nodosum). Specific attention is given to the adaptation of the Dothideomycetes to the marine milieu, new lineages of marine fungi and their host specificity