Build Robust Local Organizations (Policy Brief)

Local organizations play a valuable role in managing scarcity and competition as well as in pioneering new approaches to adaptation. Thus they are critical actors in avoiding and resolving conflict. Ensuring that local communities enjoy full recognition and fulfilment of their human and cultural rights to pursue locally-valued and legitimate governance, including their traditional normative and governance systems, is an intrinsic part of facilitating decisions that are conflict sensitive

Activation of the maternal immune system induces endocrine changes in the placenta via IL-6

Activation of the maternal immune system in rodent models sets in motion a cascade of molecular pathways that ultimately result in autism- and schizophrenia-related behaviors in offspring. The finding that interleukin-6 (IL-6) is a crucial mediator of these effects led us to examine the mechanism by which this cytokine influences fetal development in vivo. Here we focus on the placenta as the site of direct interaction between mother and fetus and as a principal modulator of fetal development. We find that maternal immune activation (MIA) with a viral mimic, synthetic double-stranded RNA (poly(I:C)), increases IL-6 mRNA as well as maternally-derived IL-6 protein in the placenta. Placentas from MIA mothers exhibit increases in CD69+ decidual macrophages, granulocytes and uterine NK cells, indicating elevated early immune activation. Maternally-derived IL-6 mediates activation of the JAK/STAT3 pathway specifically in the spongiotrophoblast layer of the placenta, which results in expression of acute phase genes. Importantly, this parallels an IL-6-dependent disruption of the growth hormone-insulin-like growth factor (GH-IGF) axis that is characterized by decreased GH, IGFI and IGFBP3 levels. In addition, we observe an IL-6-dependent induction in pro-lactin-like protein-K (PLP-K) expression as well as MIA-related alterations in other placental endocrine factors. Together, these IL-6-mediated effects of MIA on the placenta represent an indirect mechanism by which MIA can alter fetal development

Antigone in the Anthropocene: From Neoliberalism to a New Conservation Ethic

The global environmental outlook is increasingly bleak and the human condition does not fare better. The IUCN Red List of endangered species is longer than ever, with predictions foretelling the greatest mass extinction since the dinosaurs.[1] Human development reports reflect growth but do not measure well-being, deep inequality or apathy.[2] A hundred years ago, North America was coming out of a war fought overseas and entering an era of fossil fuel electrified industrialization. It was claimed that economic \u27progress\u27 would inspire efficient use of resources, but rather what it transpired was reckless waste of natural capital and an epoch of environmental crises, the Anthropocene, defined by overwhelming anthropogenically induced environmental change.[3] Narratives on peak oil, disasters, resource wars, and water and food insecurity challenge all paradigms, including law and legal systems. The Anthropocene has been derived in part through the mechanization of exploitation and commodification of Nature through a regulatory structure known as \u27law.\u27 Positive laws have been crafted to protect Nature but struggle against economic forces and there is no rule as to when Nature or Neoliberalism wins, except as determined by political whim.[4] Part of weathering the Anthropocene must involve the mechanism most systematically used for governing human behavior, the law, and in so doing, it should look to that theory of law which is most concerned with promoting justice and good human behavior, the natural law. In other words, natural law is the ideal toward which positive laws should converge. However, there have been naturalist scholars throughout the Enlightenment and Industrial eras who have seen human domination of Nature as a universal mandate. As the Anthropocene indicates, those self-serving interpretations are errant.[5] [1] International Union for the Conservation of Nature [IUCN], The IUCN Red List of Threatened Species (2011), http://www.iucnredlist.org/.; Secretariat of the Convention on Biological Diversity, Global Biodiversity Outlook 3 (2010). [2] United Nations Development Programme [UNDP], Human Development Report 2010 (2010).; United Nations Department of Economic and Social Affairs [UNDESA], The Millennium Development Goals: Report 2010 (2010).; New Economics Foundation, The UnHappy Planet Index 2.0: Why Good Loves Don\u27t Have to Cost the Earth (2009). [3] Jan Zalasiewicz et al., Are We Now Living in the Anthropocene?, 18 GSA Today 4-8 (2008). [4] Cormac Cullinan, Wild Law: Governing People for Earth (2002). [5] Robyn Eckersley, Environmentalism and Political Theory: Toward an Ecocentric Approach (New York: State University of New York Press, 1992) at 25

Peace Parks for Mountain Forests: The Law and Policy of Transforming Conflict to Stewardship

Peace parks provide a land ethic that transcends borders and seeks to stabilize tensions between bordering States, honoring the unity of biosphere systems in its efforts to achieve peace, conservation and cooperation. In theory, peace parks recognize that humans and the biosphere are one and that natural resources, just as cultural resources, must be collaboratively protected. In the cases of inhabited border regions, peace park principles of holistic conservation, cooperation and peace require that local communities be incorporated into park management. I posit that this is all the more true for frontier communities in regions of conflict, weak governance or political instability. This paper examines legal frameworks for instituting peace parks by local communities themselves, when action on the part of their governments is absent or counter-productive. In doing so, I will comparatively analyze transboundary protected areas in different regions of the world, extracting useful legal mechanisms that best reflect peace park principles. I focus this study on transboundary mountain regions because they demonstrate many valuable attributes, such as forests or watershed tributaries, and are oftentimes inhabited by marginalized communities. Degraded environments and disenfranchised peoples are particularly vulnerable to conflict and border strife (they are difficult to defend or reach), making such areas particularly interesting for a study on cross-border collaborative conservation

Maternal immune activation alters nonspatial information processing in the hippocampus of the adult offspring

The observation that maternal infection increases the risk for schizophrenia in the offspring suggests that the maternal immune system plays a key role in the etiology of schizophrenia. In a mouse model, maternal immune activation (MIA) by injection of poly(I:C) yields adult offspring that display abnormalities in a variety of behaviors relevant to schizophrenia. As abnormalities in the hippocampus are a consistent observation in schizophrenia patients, we examined synaptic properties in hippocampal slices prepared from the offspring of poly(I:C)- and saline-treated mothers. Compared to controls, CA1 pyramidal neurons from adult offspring of MIA mothers display reduced frequency and increased amplitude of miniature excitatory postsynaptic currents. In addition, the specific component of the temporoammonic pathway that mediates object-related information displays increased sensitivity to dopamine. To assess hippocampal network function in vivo, we used expression of the immediate-early gene, c-Fos, as a surrogate measure of neuronal activity. Compared to controls, the offspring of poly(I:C)-treated mothers display a distinct c-Fos expression pattern in area CA1 following novel object, but not novel location, exposure. Thus, the offspring of MIA mothers may have an abnormality in modality-specific information processing. Indeed, the MIA offspring display enhanced discrimination in a novel object recognition, but not in an object location, task. Thus, analysis of object and spatial information processing at both synaptic and behavioral levels reveals a largely selective abnormality in object information processing in this mouse model. Our results suggest that altered processing of object-related information may be part of the pathogenesis of schizophrenia-like cognitive behaviors

Maternal immune activation causes age- and region-specific changes in brain cytokines in offspring throughout development

Maternal infection is a risk factor for autism spectrum disorder (ASD) and schizophrenia (SZ). Indeed, modeling this risk factor in mice through maternal immune activation (MIA) causes ASD- and SZ-like neuropathologies and behaviors in the offspring. Although MIA upregulates pro-inflammatory cytokines in the fetal brain, whether MIA leads to long-lasting changes in brain cytokines during postnatal development remains unknown. Here, we tested this possibility by measuring protein levels of 23 cytokines in the blood and three brain regions from offspring of poly(I:C)- and saline-injected mice at five postnatal ages using multiplex arrays. Most cytokines examined are present in sera and brains throughout development. MIA induces changes in the levels of many cytokines in the brains and sera of offspring in a region- and age-specific manner. These MIA-induced changes follow a few, unexpected and distinct patterns. In frontal and cingulate cortices, several, mostly pro-inflammatory, cytokines are elevated at birth, followed by decreases during periods of synaptogenesis and plasticity, and increases again in the adult. Cytokines are also altered in postnatal hippocampus, but in a pattern distinct from the other regions. The MIA-induced changes in brain cytokines do not correlate with changes in serum cytokines from the same animals. Finally, these MIA-induced cytokine changes are not accompanied by breaches in the blood–brain barrier, immune cell infiltration or increases in microglial density. Together, these data indicate that MIA leads to long-lasting, region-specific changes in brain cytokines in offspring—similar to those reported for ASD and SZ—that may alter CNS development and behavior

The Placental Interleukin-6 Signaling Controls Fetal Brain Development and Behavior

Epidemiological studies show that maternal immune activation (MIA) during pregnancy is a risk factor for autism. However, mechanisms for how MIA affects brain development and behaviors in offspring remain poorly described. To determine whether placental interleukin-6 (IL-6) signaling is required for mediating MIA on the offspring, we generated mice with restricted deletion of the receptor for IL-6 (IL-6R_) in placental trophoblasts (Cyp19-Cre^(+);Il6ra^(fl/fl)), and tested offspring of Cyp19-Cre^(+);Il6ra^(fl/fl) mothers for immunological, pathological and behavioral abnormalities following induction of MIA. We reveal that MIA results in acute inflammatory responses in the fetal brain. Lack of IL-6 signaling in trophoblasts effectively blocks MIA-induced inflammatory responses in the placenta and the fetal brain. Furthermore, behavioral abnormalities and cerebellar neuropathologies observed in MIA control offspring are prevented in Cyp19-Cre^(+);Il6ra^(fl/fl) offspring. Our results demonstrate that IL-6 activation in placenta is required for relaying inflammatory signals to the fetal brain and impacting behaviors and neuropathologies relevant to neurodevelopmental disease

Defining Dysbiosis in Disorders of Movement and Motivation

The gut microbiota has emerged as a critical player in shaping and modulating brain function and has been shown to influence numerous behaviors, including anxiety and depression-like behaviors, sociability, and cognition. However, the effects of the gut microbiota on specific disorders associated with thalamo-cortico-basal ganglia circuits, ranging from compulsive behavior and addiction to altered sensation and motor output, are only recently being explored. Wholesale depletion and alteration of gut microbial communities in rodent models of disorders, such as Parkinson's disease, autism, and addiction, robustly affect movement and motivated behavior. A new frontier therefore lies in identifying specific microbial alterations that affect these behaviors and understanding the underlying mechanisms of action. Comparing alterations in gut microbiota across multiple basal-ganglia associated disease states allows for identification of common mechanistic pathways that may interact with distinct environmental and genetic risk factors to produce disease-specific outcomes

Integration of postpartum healthcare services for HIV-infected women and their infants in South Africa: A randomised controlled trial

Background As the number of HIV-infected women initiating lifelong antiretroviral therapy (ART) during pregnancy increases globally, concerns have emerged regarding low levels of retention in HIV services and suboptimal adherence to ART during the postpartum period. We examined the impact of integrating postpartum ART for HIV+ mothers alongside infant follow-up within maternal and child health (MCH) services in Cape Town, South Africa. Methods and findings We conducted a randomised trial among HIV+ postpartum women aged ≥18 years who initiated ART during pregnancy in the local antenatal care clinic and were breastfeeding when screened before 6 weeks postpartum. We compared an integrated postnatal service among mothers and their infants (the MCH-ART intervention) to the local standard of care (control)—immediate postnatal referral of HIV+ women on ART to general adult ART services and their infants to separate routine infant follow-up. Evaluation data were collected through medical records and trial measurement visits scheduled and located separately from healthcare services involved in either arm. The primary trial outcome was a composite endpoint of women’s retention in ART care and viral suppression (VS) (viral load < 50 copies/ml) at 12 months postpartum; secondary outcomes included duration of any and exclusive breastfeeding, mother-to-child HIV transmission, and infant mortality. Between 5 June 2013 and 10 December 2014, a total of 471 mother–infant pairs were enrolled and randomised (mean age, 28.6 years; 18% nulliparous; 57% newly diagnosed with HIV in pregnancy; median duration of ART use at randomisation, 18 weeks). Among 411 women (87%) with primary endpoint data available, 77% of women (n = 155) randomised to the MCH-ART intervention achieved the primary composite outcome of retention in ART services with VS at 12 months postpartum, compared to 56% of women (n = 117) randomised to the control arm (absolute risk difference, 0.21; 95% CI: 0.12–0.30; p < 0.001). The findings for improved retention in care and VS among women in the MCH-ART intervention arm were consistent across subgroups of participants according to demographic and clinical characteristics. The median durations of any breastfeeding and exclusive breastfeeding were longer in women randomised to the intervention versus control arm (6.9 versus 3.0 months, p = 0.006, and 3.0 versus 1.4 months, p < 0.001, respectively). For the infants, overall HIV-free survival through 12 months of age was 97%: mother-to-child HIV transmission was 1.2% overall (n = 4 and n = 1 transmissions in the intervention and control arms, respectively), and infant mortality was 1.9% (n = 6 and n = 3 deaths in the intervention and control arms, respectively), and these outcomes were similar by trial arm. Interpretation of these findings should be qualified by the location of this study in a single urban area as well as the self-reported nature of breastfeeding outcomes. Conclusions In this study, we found that integrating ART services into the MCH platform during the postnatal period was a simple and effective intervention, and this should be considered for improving maternal and child outcomes in the context of HIV