Human well‐being and climate change mitigation

Climate change mitigation research is fundamentally motivated by the preservation of human lives and the environmental conditions which enable them. However, the field has to date rather superficial in its appreciation of theoretical claims in well‐being thought, with deep implications for the framing of mitigation priorities, policies, and research. Major strands of well‐being thought are hedonic well‐being—typically referred to as happiness or subjective well‐being—and eudaimonic well‐being, which includes theories of human needs, capabilities, and multidimensional poverty. Aspects of each can be found in political and procedural accounts such as the Sustainable Development Goals. Situating these concepts within the challenges of addressing climate change, the choice of approach is highly consequential for: (1) understanding inter‐ and intra‐generational equity; (2) defining appropriate mitigation strategies; and (3) conceptualizing the socio‐technical provisioning systems that convert biophysical resources into well‐being outcomes. Eudaimonic approaches emphasize the importance of consumption thresholds, beyond which dimensions of well‐being become satiated. Related strands of well‐being and mitigation research suggest constraining consumption to within minimum and maximum consumption levels, inviting normative discussions on the social benefits, climate impacts, and political challenges associated with a given form of provisioning. The question of how current socio‐technical provisioning systems can be shifted towards low‐carbon, well‐being enhancing forms constitutes a new frontier in mitigation research, involving not just technological change and economic incentives, but wide‐ranging social, institutional, and cultural shifts

Contribution of human hematopoietic stem cells to liver repair

Immune-deficient mouse models of liver damage allow examination of human stem cell migration to sites of damage and subsequent contribution to repair and survival. In our studies, in the absence of a selective advantage, transplanted human stem cells from adult sources did not robustly become hepatocytes, although some level of fusion or hepatic differentiation was documented. However, injected stem cells did home to the injured liver tissue and release paracrine factors that hastened endogenous repair and enhanced survival. There were significantly higher levels of survival in mice with a toxic liver insult that had been transplanted with human stem cells but not in those transplanted with committed progenitors. Transplantation of autologous adult stem cells without conditioning is a relatively safe therapy. Adult stem cells are known to secrete bioactive factors that suppress the local immune system, inhibit fibrosis (scar formation) and apoptosis, enhance angiogenesis, and stimulate recruitment, retention, mitosis, and differentiation of tissue-residing stem cells. These paracrine effects are distinct from the direct differentiation of stem cells to repair tissue. In patients at high risk while waiting for a liver transplant, autologous stem cell therapy could be considered, as it could delay the decline in liver function

Analysis of Marker-Defined HNSCC Subpopulations Reveals a Dynamic Regulation of Tumor Initiating Properties

Head and neck squamous carcinoma (HNSCC) tumors carry dismal long-term prognosis and the role of tumor initiating cells (TICs) in this cancer is unclear. We investigated in HNSCC xenografts whether specific tumor subpopulations contributed to tumor growth. We used a CFSE-based label retentions assay, CD49f (α6-integrin) surface levels and aldehyde dehydrogenase (ALDH) activity to profile HNSCC subpopulations. The tumorigenic potential of marker-positive and -negative subpopulations was tested in nude (Balb/c nu/nu) and NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) mice and chicken embryo chorioallantoic membrane (CAM) assays. Here we identified in HEp3, SQ20b and FaDu HNSCC xenografts a subpopulation of G0/G1-arrested slow-cycling CD49fhigh/ALDH1A1high/H3K4/K27me3low subpopulation (CD49f+) of tumor cells. A strikingly similar CD49fhigh/H3K27me3low subpopulation is also present in primary human HNSCC tumors and metastases. While only sorted CD49fhigh/ALDHhigh, label retaining cells (LRC) proliferated immediately in vivo, with time the CD49flow/ALDHlow, non-LRC (NLRC) tumor cell subpopulations were also able to regain tumorigenic capacity; this was linked to restoration of CD49fhigh/ALDHhigh, label retaining cells. In addition, CD49f is required for HEp3 cell tumorigenicity and to maintain low levels of H3K4/K27me3. CD49f+ cells also displayed reduced expression of the histone-lysine N-methyltransferase EZH2 and ERK1/2phosphorylation. This suggests that although transiently quiescent, their unique chromatin structure is poised for rapid transcriptional activation. CD49f− cells can “reprogram” and also achieve this state eventually. We propose that in HNSCC tumors, epigenetic mechanisms likely driven by CD49f signaling dynamically regulate HNSCC xenograft phenotypic heterogeneity. This allows multiple tumor cell subpopulations to drive tumor growth suggesting that their dynamic nature renders them a “moving target” and their eradication might require more persistent strategies

Shielding intentions from distraction: Forming an intention induces inhibition of distracting stimuli

Contains fulltext : 56393.pdf (publisher's version ) (Open Access)Previous research has shown that focal goals are shielded through inhibition of alternative goals. The present research aims to extend these findings and show that execution of experimentally induced intentions is also shielded from distraction. In two experiments participants were instructed to form an intention to react to specific stimuli (intention cues). Next, we assessed accessibility of the intention cues, distracting cues and control cues. Results show that distracting cues were inhibited compared with control cues. In addition, we obtained preliminary evidence that this inhibition facilitates execution of previously formed intentions. The present research adds to earlier research on intentions and goal shielding by showing that cognitive self–regulatory processes shield intentions from distraction.17 p