Neighbourhood Matters for Peacebuilding

Academic and political debates on peace and conflict dynamics increasingly acknowledge the relevance of the interaction between global and subnational or local dynamics but rather neglect the regional neighbourhood as an important intervening variable. The concept of "regional peace formations" either as an enabling or hindering factor for peacebuilding fills this gap. Empirical evidence from Latin America, the Middle East, and sub-Saharan Africa shows the added value of the concept for explaining regional differences. Peacebuilding is a complex undertaking shaped by a variety of factors such as the nature of conflicts, the actors involved, and local contexts. A regional perspective regarding patterns of conflict and violence shows high levels of variation between regions. The concept of regional peace formations is an important tool to analyse the region-specific variation in actors and conflict dynamics. It allows us to identify either convergent or divergent contexts for peacebuilding. Empirical evidence from Latin America, the Middle East, and sub-Saharan Africa identifies relevant differences and the need to incorporate regional factors into peacebuilding strategies. The regional level of peacebuilding offers the possibility for meaningful donor coordination and joint multilateral action. But a minimalistic approach seeking only the end of war or a certain degree of stabilisation is not enough. Initiatives need a clear focus on long-term peacebuilding, as a process of constructive conflict transformation. Regional economic and social networks are central to sustainable development, and to transforming structural conditions - leading either to the violent escalation of conflict or to the fostering of more peaceful societies

Investigating the persistence of tick-borne pathogens via the R0 model

In the epidemiology of infectious diseases, the basic reproduction number,R0, has a number of important applications, most notably it can be used to predict whether a pathogen is likely to become established, or persist, in a given area. We used the R0 model to investigate the persistence of 3 tick-borne pathogens; Babesia microti, Anaplasma phagocytophilum and Borrelia burgdorferi sensu lato in an Apodemus sylvaticus-Ixodes ricinus system. The persistence of these pathogens was also determined empirically by screening questing ticks and wood mice by PCR. All 3 pathogens behaved differently in response to changes in the proportion of transmission hosts on which I. ricinus fed, the efficiency of transmission between the host and ticks and the abundance of larval and nymphal ticks found on small mammals. Empirical data supported theoretical predictions of the R0 model. The transmission pathway employed and the duration of systemic infection were also identified as important factors responsible for establishment or persistence of tick-borne pathogens in a given tick-host system. The current study demonstrates how the R0 model can be put to practical use to investigate factors affecting tick-borne pathogen persistence, which has important implications for animal and human health worldwide

BAP1 regulates epigenetic switch from pluripotency to differentiation in developmental lineages giving rise to BAP1-mutant cancers

The BAP1 tumor suppressor is mutated in many human cancers such as uveal melanoma, leading to poor patient outcome. It remains unclear how BAP1 functions in normal biology or how its loss promotes cancer progression. Here, we show that Bap1 is critical for commitment to ectoderm, mesoderm, and neural crest lineages during Xenopus laevis development. Bap1 loss causes transcriptional silencing and failure of H3K27ac to accumulate at promoters of key genes regulating pluripotency-to-commitment transition, similar to findings in uveal melanoma. The Bap1-deficient phenotype can be rescued with human BAP1, by pharmacologic inhibition of histone deacetylase (HDAC) activity or by specific knockdown of Hdac4. Similarly, BAP1-deficient uveal melanoma cells are preferentially vulnerable to HDAC4 depletion. These findings show that Bap1 regulates lineage commitment through H3K27ac-mediated transcriptional activation, at least in part, by modulation of Hdac4, and they provide insights into how BAP1 loss promotes cancer progression.Fil: Kuznetsov, Jeffim N.. University of Miami; Estados UnidosFil: Agüero, Tristán Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. University of Miami; Estados UnidosFil: Owens, Dawn A.. University of Miami; Estados UnidosFil: Kurtenbach, Stefan. University of Miami; Estados UnidosFil: Field, Matthew G.. University of Miami; Estados UnidosFil: Durante, Michael A.. University of Miami; Estados UnidosFil: Rodriguez, Daniel A.. University of Miami; Estados UnidosFil: King, Mary Lou. University of Miami; Estados UnidosFil: Harbour, J. William. University of Miami; Estados Unido

Borrelia valaisiana resist complement-mediated killing independently of the recruitment of immune regulators and inactivation of complement components

Spirochetes belonging to the Borrelia (B.) burgdorferi sensu lato complex differ in their resistance to complement-mediated killing, particularly in regard to human serum. In the present study, we elucidate the serum and complement susceptibility of B. valaisiana, a genospecies with the potential to cause Lyme disease in Europe as well as in Asia. Among the investigated isolates, growth of ZWU3 Ny3 was not affected while growth of VS116 and Bv9 was strongly inhibited in the presence of 50% human serum. Analyzing complement activation, complement components C3, C4 and C6 were deposited on the surface of isolates VS116 and Bv9, and similarly the membrane attack complex was formed on their surface. In contrast, no surface-deposited components and no aberrations in cell morphology were detected for serum-resistant ZWU3 Ny3. While further investigating the protective role of bound complement regulators in mediating complement resistance, we discovered that none of the B. valaisiana isolates analyzed bound complement regulators Factor H, Factor H-like protein 1, C4b binding protein or C1 esterase inhibitor. In addition, B. valaisiana also lacked intrinsic proteolytic activity to degrade complement components C3, C3b, C4, C4b, and C5. Taken together, these findings suggest that certain B. valaisiana isolates differ in their capability to resist complement-mediating killing by human serum. The molecular mechanism utilized by B. valaisiana to inhibit bacteriolysis appears not to involve binding of the key host complement regulators of the alternative, classical, and lectin pathways as already known for serum-resistant Lyme disease or relapsing fever borreliae

Stacked crop rotations and cultural practices for canola and flax yield and quality

Canola (Brassica napus L.) and flax (Linum usitatissimum L.) are important oilseed crops, but improved management practices to enhance their yields and quality are needed. We studied the effect of stacked versus alternate‐year crop rotations and traditional versus improved cultural practices on canola and flax growth, seed yield, oil concentration, and N‐use efficiency from 2006 to 2011 in the northern Great Plains, USA. Stacked rotations were durum (Triticum turgidum L.)‐durum‐canola‐pea (Pisum sativum L.) (DDCP) and durum‐durum‐flax‐pea (DDFP). Alternate‐year rotations were durum‐canola‐durum‐pea (DCDP) and durum‐flax‐durum‐pea (DFDP). The traditional cultural practice included a combination of conventional tillage, recommended seed rate, broadcast N fertilization, and reduced stubble height. The improved cultural practice included a combination of no‐tillage, increased seed rate, banded N fertilization, and increased stubble height. Canola stand count was 36–123% greater with the improved than the traditional cultural practice in 2006, 2009, 2010, and 2011. Canola pod number and oil concentration were 3–36% greater in the improved than the traditional practice in 2007 and 2010, but trends reversed by 5–19% in 2008. Flax stand count was 28% greater with DFDP than DDFP in 2007 and 56% greater in the improved than the traditional practice in 2010. Flax pod number, seed weight, seed yield, N content, N‐use efficiency, and N‐removal index varied with crop rotations, cultural practices, and years. Canola growth and oil concentration increased with the improved cultural practice as well as flax growth, yield, and quality enhanced with alternate‐year crop rotation and the improved cultural practice in wet years

The Parmodulin NRD-21 is an Allosteric Inhibitor of PAR1 Gq Signaling with Improved Anti-Inflammatory Activity and Stability

Novel analogs of the allosteric, biased PAR1 ligand ML161 (parmodulin 2, PM2) were prepared in order to identify potential anti-thrombotic and anti-inflammatory compounds of the parmodulin class with improved properties. Investigations of structure-activity relationships of the western portion of the 1,3-diaminobenzene scaffold were performed using an intracellular calcium mobilization assay with endothelial cells, and several heterocycles were identified that inhibited PAR1 at sub-micromolar concentrations. The oxazole NRD-21 was profiled in additional detail, and it was confirmed to act as a selective, reversible, negative allosteric modulator of PAR1. In addition to inhibiting human platelet aggregation, it showed superior anti-inflammatory activity to ML161 in a qPCR assay measuring the expression of tissue factor in response to the cytokine TNF-alpha in endothelial cells. Additionally, NRD-21 is much more plasma stable than ML161, and is a promising lead compound for the parmodulin class for anti-thrombotic and anti-inflammatory indications

Fine-Scale Phylogeographic Structure of Borrelia lusitaniae Revealed by Multilocus Sequence Typing

Borrelia lusitaniae is an Old World species of the Lyme borreliosis (LB) group of tick-borne spirochetes and prevails mainly in countries around the Mediterranean Basin. Lizards of the family Lacertidae have been identified as reservoir hosts of B. lusitaniae. These reptiles are highly structured geographically, indicating limited migration. In order to examine whether host geographic structure shapes the evolution and epidemiology of B. lusitaniae, we analyzed the phylogeographic population structure of this tick-borne bacterium using a recently developed multilocus sequence typing (MLST) scheme based on chromosomal housekeeping genes. A total of 2,099 questing nymphal and adult Ixodes ricinus ticks were collected in two climatically different regions of Portugal, being ∼130 km apart. All ticks were screened for spirochetes by direct PCR. Attempts to isolate strains yielded 16 cultures of B. lusitaniae in total. Uncontaminated cultures as well as infected ticks were included in this study. The results using MLST show that the regional B. lusitaniae populations constitute genetically distinct populations. In contrast, no clear phylogeographic signals were detected in sequences of the commonly used molecular markers ospA and ospC. The pronounced population structure of B. lusitaniae over a short geographic distance as captured by MLST of the housekeeping genes suggests that the migration rates of B. lusitaniae are rather low, most likely because the distribution of mediterranean lizard populations is highly parapatric. The study underlines the importance of vertebrate hosts in the geographic spread of tick-borne microparasites