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"Keller, Eva"
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Beyond the Lens of Conservation
The global agenda of Nature conservation has led to the creation of the Masoala National Park in Madagascar and to an exhibit in its support at a Swiss zoo, the centerpiece of which is a mini-rainforest replica. Does such a cooperation also trigger a connection between ordinary people in these two far-flung places? The study investigates how the Malagasy farmers living at the edge of the park perceive the conservation enterprise and what people in Switzerland see when looking towards Madagascar through the lens of the zoo exhibit. It crystallizes that the stories told in either place have almost nothing in common: one focuses on power and history, the other on morality and progress. Thus, instead of building a bridge, Nature conservation widens the gap between people in the North and the South.
eBook
The road to clarity : Seventh-Day Adventism in Madagascar
In recent years, millions of people have joined churches such as the Seventh-day Adventist which prosper enormously in different parts of the world. The Road to Clarity is one of the first ethnographic in-depth studies of this phenomenon. It is a vivid account based on almost two years of participation in ordinary church members' daily religious and non-religious lives. The book offers a fascinating inquiry into the nature of long-term commitment to Adventism among rural people in Madagascar. Eva Keller argues that the key attraction of the church lies in the excitement of study, argument and intellectual exploration. This is a novel approach which challenges utilitarian and cultural particularist explanations of the success of this kind of Christianity.
eBook
MLKL promotes cellular differentiation in myeloid leukemia by facilitating the release of G-CSF
The blockade of cellular differentiation represents a hallmark of acute myeloid leukemia (AML), which is largely attributed to the dysfunction of lineage-specific transcription factors controlling cellular differentiation. However, alternative mechanisms of cellular differentiation programs in AML remain largely unexplored. Here we report that mixed lineage kinase domain-like protein (MLKL) contributes to the cellular differentiation of transformed hematopoietic progenitor cells in AML. Using gene-targeted mice, we show that MLKL facilitates the release of granulocyte colony-stimulating factor (G-CSF) by controlling membrane permeabilization in leukemic cells.
Mlkl
−/−
hematopoietic stem and progenitor cells released reduced amounts of G-CSF while retaining their capacity for
CSF3
(G-CSF) mRNA expression, G-CSF protein translation, and G-CSF receptor signaling. MLKL associates with early endosomes and controls G-CSF release from intracellular storage by plasma membrane pore formation, whereas cell death remained unaffected by loss of MLKL. Of note,
MLKL
expression was significantly reduced in AML patients, specifically in those with a poor-risk AML subtype. Our data provide evidence that MLKL controls myeloid differentiation in AML by controlling the release of G-CSF from leukemic progenitor cells.
Journal Article
Chromatin accessibility mapping of the striatum identifies tyrosine kinase FYN as a therapeutic target for heroin use disorder
The current opioid epidemic necessitates a better understanding of human addiction neurobiology to develop efficacious treatment approaches. Here, we perform genome-wide assessment of chromatin accessibility of the human striatum in heroin users and matched controls. Our study reveals distinct neuronal and non-neuronal epigenetic signatures, and identifies a locus in the proximity of the gene encoding tyrosine kinase
FYN
as the most affected region in neurons.
FYN
expression, kinase activity and the phosphorylation of its target Tau are increased by heroin use in the post-mortem human striatum, as well as in rats trained to self-administer heroin and primary striatal neurons treated with chronic morphine in vitro. Pharmacological or genetic manipulation of FYN activity significantly attenuates heroin self-administration and responding for drug-paired cues in rodents. Our findings suggest that striatal FYN is an important driver of heroin-related neurodegenerative-like pathology and drug-taking behavior, making FYN a promising therapeutic target for heroin use disorder.
Epigenetic mechanisms have emerged as contributors to the molecular impairments caused by exposure to environmental factors such as abused substances. Here the authors perform epigenetic profiling of the striatum and identify the tyrosine kinase FYN is an important driver of neurodegenerative-like pathology and drug-taking behaviour.
Journal Article
Opioid neuropeptide genotypes in relation to heroin abuse: Dopamine tone contributes to reversed mesolimbic proenkephalin expression
Striatal enkephalin and dynorphin opioid systems mediate reward and negative affect, respectively, relevant to addiction disorders. We examined polymorphisms of proenkephalin (PENK) and prodynorphin (PDYN) genes in relation to heroin abuse and gene expression in the human striatum and the relevance of genetic dopaminergic tone, critical for drug reward and striatal function. Heroin abuse was significantly associated with PENK polymorphic 3' UTR dinucleotide (CA) repeats; 79% of subjects homozygous for the 79-bp allele were heroin abusers. Such individuals tended to express higher PENK mRNA than the 81-bp homozygotes, but PENK levels within the nucleus accumbens (NAc) shell were most strongly correlated to catecholamine-O-methyltransferase (COMT) genotype. Control Met/Met individuals expressed lower PENK mRNA than Val carriers, a pattern reversed in heroin users. Up-regulation of NAc PENK in Met/Met heroin abusers was accompanied by impaired tyrosine hydroxylase (TH) mRNA expression in mesolimbic dopamine neurons. In contrast to PENK, no association was detected between PDYN genotype (68-bp repeat element containing one to four copies of AP-1 binding sites in the promoter region) and heroin abuse, although there was a clear functional association with striatal PDYN mRNA expression: an increased number of inducible repeats (three and four) correlated with higher PDYN levels than adult or fetal subjects with noninducible (one and two) alleles. Moreover, PDYN expression was not related to COMT genotype. Altogether, the data suggest that dysfunction of the opioid reward system is significantly linked to opiate abuse vulnerability and that heroin use alters the apparent influence of heritable dopamine tone on mesolimbic PENK and TH function.
Journal Article
Frequency and structure of stimulant designer drug consumption among suspected drug users in Budapest and South-East Hungary in 2012–2013
•Stimulant designer drug (SDD) consumption was compared in two regions of Hungary.•Target population: suspected drug users in Budapest and South-East Hungary.•In 2012–2013 pentedrone was the most frequently used stimulant designer drug.•The frequency of the other SDDs showed differences in the two areas.•Consumption of SDDs highly decreased after listing them on illicit drug registry.
Identification of abuse and frequency patterns of stimulant designer drugs (SDDs) provides important information for their risk assessment and legislative control. In the present study urine and/or blood samples of suspected drug users in criminal cases were analysed by GC–MS for 38 SDDs, and for the most frequent illicit and psychoactive licit drugs in Hungary. Between July 2012 and June 2013, 2744 suspected drug users were sampled in Budapest and during 2012 and 2013, 774 persons were sampled in South-East Hungary (Csongrád County – neighbour the Romanian and Serbian borders). In Budapest 71.4% of cases, and in South-East Hungary 61% of cases were positive for at least one substance. Pentedrone was the most frequent SDD in both regions; however, the frequency distribution of the remaining drugs was highly diverse. SDDs were frequently present in combination with other drugs – generally with amphetamine or other stimulants, cannabis and/or benzodiazepines. The quarterly distribution of positive samples indicated remarkable seasonal changes in the frequency and pattern of consumption. Substances placed on the list of illicit drugs (mephedrone, 4-fluoro-amphetamine, MDPV, methylone, 4-MEC) showed a subsequent drop in frequency and were replaced by other SDDs (pentedrone, 3-MMC, methiopropamine, etc.). Newly identified compounds from seized materials were added to the list of new psychoactive substances (“Schedule C”). While the risk assessment of substances listed in Schedule C has to be performed within 2 years after scheduling, continuous monitoring of their presence and frequency among drug users is essential. In summary, our results suggest which substances should be dropped from the list of SDDs measured in biological samples; while the appearance of new substances from seized materials indicate the need for developing adequate standard analytical methods.
Journal Article
The banana plant and the moon: Conservation and the Malagasy ethos of life in Masoala, Madagascar
For people in rural Madagascar, the growth of one's kin group and the joint processes of movement and anchorage in the land are fundamental aspects of a successful life. In this article, I examine the clash between the Malagasy ethos of growth and the canonical conservationist ethos of static equilibrium. I argue that biodiversity conservation on the Masoala peninsula leaves local people with a sense of having been defeated in the purpose of life as they understand it. I further suggest that, in the case of people of slave descent, such defeat reverses the historical process of shedding slave status.
Journal Article
μ Opioid Receptor A118G Polymorphism in Association with Striatal Opioid Neuropeptide Gene Expression in Heroin Abusers
μ Opioid receptors are critical for heroin dependence, and A118G SNP of the μ opioid receptor gene (OPRM1) has been linked with heroin abuse. In our population of European Caucasians (n = 118), ≈90% of 118G allelic carriers were heroin users. Postmortem brain analyses showed the OPRM1 genotype associated with transcription, translation, and processing of the human striatal opioid neuropeptide system. Whereas down-regulation of preproenkephalin and preprodynorphin genes was evident in all heroin users, the effects were exaggerated in 118G subjects and were most prominent for preproenkephalin in the nucleus accumbens shell. Reduced opioid neuropeptide transcription was accompanied by increased dynorphin and enkephalin peptide concentrations exclusively in 118G heroin subjects, suggesting that the peptide processing is associated with the OPRM1 genotype. Abnormal gene expression related to peptide convertase and ubiquitin/proteosome regulation was also evident in heroin users. Taken together, alterations in opioid neuropeptide systems might underlie enhanced opiate abuse vulnerability apparent in 118G individuals.
Journal Article