Which Wisdom Can Change the World?

The thoughts that Michel Puech formulates on wisdom, technology and the art of living are timely at a moment when social, ecological and economic problems are pressing upon our societies and the speed of technological development seems to overwhelm our ability to integrate and adapt new technologies in our lives and societies. However, he restricts his concept of wisdom too much to a personal endeavor and overestimates the relevance of non-confrontation. I argue that his project can only be of value when it is embedded in a broader societal and political strategy for change.     

Examining ecological consequences of feral horse grazing using exclosures

Although feral horses have inhabited western North America since the end of the 16th century, relatively little synecological research has been conducted to quantitatively characterize how they interact with ecosystem components. Because feral horses exhibit watering behavior markedly different from that of domestic cattle, it is particularly important to evaluate response of ecosystem elements near water sources to horse use. To assess this response, we performed live-trapping of small mammals and 2-tiered vegetative sampling in 2 mountain ranges in central Nevada in the interior Great Basin, USA. At low elevations, plots around horse-excluded springs exhibited notably greater plant species richness, percent cover, and abundance of grasses and shrubs, as well as more small mammal burrow entrances than plots at horse-grazed springs. At high elevations, meadows protected from grazing exhibited maximum vegetation heights 2.8 times greater than vegetation grazed by horses only and 4.5 times greater than vegetation grazed by horses and cattle. Species richness in quadrats was most different between the horse-and-cattle-grazed meadow and its ungrazed counterpart, suggesting the possibility of synergistic effects of horse and cattle grazing in the same location. This study, the first in the Great Basin to investigate quantitatively ecosystem consequences of feral horse use with exclosures, represents a preliminary step in identifying factors that determine the magnitude of horse grazing impacts.     

Inflammatory bowel disease: is it a primary immunodeficiency?

Inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn’s disease are chronic and relapsing conditions, characterized by abdominal pain, diarrhea, bleeding and malabsorption. IBD has been considered a hyperinflammatory state due to disturbed interactions between the immune system and the commensal bacterial flora of the gut. However, there is evidence that Crohn’s disease might be the consequence of a reduced release of pro-inflammatory cytokines and an impaired acute inflammatory response, thereby suggesting that IBD might be an immunodeficiency rather than an excessive inflammatory reaction. This theory has been supported by observations in patients with primary immunodeficiencies such as the Wiskott–Aldrich syndrome and IPEX (immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome). In contrary, defects in the anti-inflammatory down-regulation of the immune response as they are seen in patients with Mendelian defects in the IL10 signaling pathway support the hyper-inflammatory theory. In this review, we describe and discuss primary immunodeficiencies associated with IBD and show that the bowel is a highly sensitive indicator of dysregulations, making IBD a model disease to study and identify key regulators required to balance the human mucosal immune system.     

Variation in interleukin 7 receptor alpha chain (IL7R) influences risk of multiple sclerosis

Multiple sclerosis is a chronic, often disabling, disease of the central nervous system affecting more than 1 in 1,000 people in most western countries. The inflammatory lesions typical of multiple sclerosis show autoimmune features and depend partly on genetic factors. Of these genetic factors, only the HLA gene complex has been repeatedly confirmed to be associated with multiple sclerosis, despite considerable efforts. Polymorphisms in a number of non-HLA genes have been reported to be associated with multiple sclerosis, but so far confirmation has been difficult. Here, we report compelling evidence that polymorphisms in IL7R, which encodes the interleukin 7 receptor alpha chain (IL7Ralpha), indeed contribute to the non-HLA genetic risk in multiple sclerosis, demonstrating a role for this pathway in the pathophysiology of this disease. In addition, we report altered expression of the genes encoding IL7Ralpha and its ligand, IL7, in the cerebrospinal fluid compartment of individuals with multiple sclerosis.     

Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies

To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10???) and 9q31.2 (P = 2.2 × 10?33), we identified 30 new menarche loci (all P < 5 × 10??) and found suggestive evidence for a further 10 loci (P < 1.9 × 10??). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.     

Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10?? to P = 1.8 × 10???) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10?3 to P = 1.2 × 10?13). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.     

Civic Meaningfulness

This paper starts from qualitative research on volunteering and citizenship, with a special focus on volunteering within a setting of restorative justice and mediation. In a first stage, the author reconstructs two models of meaningfulness as hermeneutical lenses to better understand how volunteers see their engagement and experiences as a source of meaningfulness. The paper argues that a biographical model of meaningfulness (Wolf’s theoretical framework) is in need of a complementary approach to meaningfulness (an existential model of meaningfulness), which focuses on transformational experiences with a strong existential depth. In a second stage, the paper dialogues with the experiences and narratives of the volunteers, and shows how their understanding of citizenship informs, and transforms their ideas of meaningfulness. Both the biographical and the existential approach to meaningfulness appear to be deeply influenced by the volunteers’ civic imaginaries.     

Crystal structure of a potassium ion transporter, TrkH

The TrkH/TrkG/KtrB proteins mediate K(+) uptake in bacteria and probably evolved from simple K(+) channels by multiple gene duplications or fusions. Here we present the crystal structure of a TrkH from Vibrio parahaemolyticus. TrkH is a homodimer, and each protomer contains an ion permeation pathway. A selectivity filter, similar in architecture to those of K(+) channels but significantly shorter, is lined by backbone and side-chain oxygen atoms. Functional studies showed that TrkH is selective for permeation of K(+) and Rb(+) over smaller ions such as Na(+) or Li(+). Immediately intracellular to the selectivity filter are an intramembrane loop and an arginine residue, both highly conserved, which constrict the permeation pathway. Substituting the arginine with an alanine significantly increases the rate of K(+) flux. These results reveal the molecular basis of K(+) selectivity and suggest a novel gating mechanism for this large and important family of membrane transport proteins.