On the role of exploitation and exploration strategies in the maintenance of cognitive biases: Beyond the pursuit of instrumental rewards

Why can initial biases persist in repeated choice tasks? Previous research has shown that frequent rewards can lure the decision maker into premature exploitation of a supposedly best option, which can result in the persistence of initial biases. Here, we demonstrate that even in the absence of rewards, initial biases can be perpetuated through a positive testing strategy. After eliciting a biased preference for one of two equally rewarding options, participants (N = 203) could sample freely from both options without the lure of any financial rewards. When participants were told to rule out alternatives in this phase, they explored the supposedly worse option and thereby managed to overcome their initial bias. When told to optimize their strategy, however, they exhibited a positive testing strategy resulting in the continued exploitation of the supposedly better option, a bias they maintained in an incentivized choice phase and later judgments. Across all participants, individual tendencies to exploit one option in earlier phases predicted biased behavior in subsequent phases. The findings highlight that not only the pursuit of instrumental rewards can lead to exploitation and the maintenance of initial biases. We discuss potential consequences for interventions

Metabolic Signature of Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma: Expression of Hypoxia-inducible Factor-1α and Several of Its Downstream Targets

Metabolic reprogramming mediated by hypoxia-inducible factors play a crucial role in many human cancers. HIF-1α is activated under hypoxic conditions and is considered a key regulator of oxygen homoeostasis during tumor proliferation under hypoxia. Aim of this research was to analyze the immunohistochemical expression of HIF-1α, VEGF-A, Glut-1, MCT4, and CAIX in atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS). 21 paraffin-embedded AFX and 22 PDS were analysed by immunohistochemis-try, namely HIF-1α, VEGF-A (referred to as VEGF throughout the manuscript), Glut-1, MCT4, and CAIX. To quantify the protein expression, we considered the percentage of positive tumor cells (0: 0%, 1: up to 1%, 2: 2-10%, 3: 11-50%, 4: >50%) in relation to the staining intensity (0: negative, 1: low, 2: medium, 3: strong). HIF-1α expression (mean ± SD) in AFX (9.33±2.92) was significantly stronger than that in PDS (5.90±4.38; P= 0.007), whereas the expression of VEGF, Glut-1, MCT4, and CAIX did not show differences between AFX and PDS. When comparing all tumors without subgroup stratification, the expression of HIF-1α (P= 0.044) and MCT4 (P= 0.036) was significantly stronger in ulcerated tumors than in tumors without ulceration. Our findings provide the first evidence that HIF-1α-induced metabolic reprogramming may contribute to the pathogenesis of AFX and PDS. HIF-1α expression seems to be higher in AFX than in PDS, and ulcerated tumors show higher expression levels of HIF-1α and MCT4 irrespective of the diagnosis

Some Unusual Properties of Turbulent Convection and Dynamos in Rotating Spherical Shells

The dynamics of convecting fluids in rotating spherical shells is governed at Prandtl numbers of the order unity by the interaction between differential rotation and roll-like convection eddies. While the differential rotation is driven by the Reynolds stresses of the eddies, its shearing action inhibits convection and causes phenomena such as localized convection and turbulent relaxation oscillations. The response of the system is enriched in the case of dynamo action. Lorentz forces may brake either entirely or partially the geostrophic differential rotation and give rise to two rather different dynamo states. Bistability of turbulent dynamos exists for magnetic Prandtl numbers of the order unity. While the ratios between mean magnetic and kinetic energies differ by a factor of 5 or more for the two dynamo states, the mean convective heat transports are nearly the same. They are much larger than in the absence of a magnetic field.Comment: To appear in Procs. IUTAM Symposium on Turbulence in the Atmosphere and Oceans, 08-7 = GA.06-0

Phosphorylation of serine-893 in CARD11 suppresses the formation and activity of the CARD11-BCL10-MALT1 complex in T and B cells

CARD 11 acts as a gatekeeper for adaptive immune responses after T cell or B cell antigen receptor (TCR/BCR) ligation on lymphocytes. PKC theta/beta-catalyzed phosphorylation of CARD11 promotes the assembly of the CARD11-BCL10-MALT1 (CBM) complex and lymphocyte activation. Here, we demonstrated that PKC theta/beta-dependent CARD11 phosphorylation also suppressed CARD11 functions in T or B cells. Through mass spectrometry-based proteomics analysis, we identified multiple constitutive and inducible CARD11 phosphorylation sites in T cells. We demonstrated that a single TCR- or BCR-inducible phosphorylation on Ser 893 in the carboxyl terminus of CARD1 1 prevented the activation of the transcription factor NF-kappa B, the kinase JNK, and the protease MALT1. Moreover, CARD11 Ser(893) phosphorylation sensitized BCR-addicted lymphoma cells to toxicity induced by Bruton's tyrosine kinase (BTK) inhibitors. Phosphorylation of Ser 893 in CARD11 by PKCO controlled the strength of CARD11 scaffolding by impairing the formation of the CBM complex. Thus, PKCO simultaneously catalyzes both stimulatory and inhibitory CARD11 phosphorylation events, which shape the strength of CARD11 signaling in lymphocytes

MALT1 Phosphorylation Controls Activation of T Lymphocytes and Survival of ABC-DLBCL Tumor Cells

The CARMA1/CARD11-BCL10-MALT1 (CBM) complex bridges T and B cell antigen receptor (TCR/BCR) ligation to MALT1 protease activation and canonical nuclear factor kappa B (NF-kappa B) signaling. Using unbiased mass spectrometry, we discover multiple serine phosphorylation sites in the MALT1 C terminus after T cell activation. Phospho-specific antibodies reveal that CBM-associated MALT1 is transiently hyper-phosphorylated upon TCR/CD28 co-stimulation. We identify a dual role for CK1 alpha as a kinase that is essential for CBM signalosome assembly as well as MALT1 phosphorylation. Although MALT1 phosphorylation is largely dispensable for protease activity, it fosters canonical NF-kappa B signaling in Jurkat and murine CD4 T cells. Moreover, constitutive MALT1 phosphorylation promotes survival of activated B cell-type diffuse large B cell lymphoma (ABC-DLBCL) cells addicted to chronic BCR signaling. Thus, MALT1 phosphorylation triggers optimal NF-kappa B activation in lymphocytes and survival of lymphoma cells

Effects of Endurance Exercise Training and Crataegus Extract WS® 1442 in Patients with Heart Failure with Preserved Ejection Fraction - A Randomized Controlled Trial

Impaired exercise capacity is the core symptom of heart failure with preserved ejection fraction (HFpEF). We assessed effects of exercise training and Crataegus extract WS 1442 in HFpEF and aimed to identify mechanisms of action in an exploratory trial (German Clinical Trials Register DRKS00000259). 140 sedentary HFpEF NYHA II patients on standard treatment received eight weeks of aerobic endurance training and half were randomized to WS 1442 900 mg/day. Symptoms, 2 km walking time (T2km), parameters of exercise tolerance, cardiac and vascular function, muscular efficiency and skeletal muscular haemoglobin oxygen saturation (SO2) measured during a treadmill protocol were captured at baseline and after eight weeks. Adverse events were recorded during the trial. Mechanisms of action were explored by correlation and path analyses of changes. Symptoms and exercise capacity improved with training, but correlations between improvements were low and path models were rejected. SO2 increased, decreased or undulated with increasing exercise intensity in individual patients and was not altered by training. WS 1442 improved T2km (-12.7% vs. -8.4%, p = 0.019), tended to improve symptoms and to pronounce SO2-decrease with increasing exercise, an indicator of oxygen utilisation. Endurance training and WS 1442 were safe and well tolerated in combination with standard drug treatment

Addressing the environmental, community and health impacts of resource development: Challenges across scales, sectors and sites

Work that addresses the cumulative impacts of resource extraction on environment, community, and health is necessarily large in scope. This paper presents experiences from initiating research at this intersection and explores implications for the ambitious, integrative agenda of planetary health. The purpose is to outline origins, design features, and preliminary insights from our intersectoral and international project, based in Canada and titled the “Environment, Community, Health Observatory” (ECHO) Network. With a clear emphasis on rural, remote, and Indigenous communities, environments, and health, the ECHO Network is designed to answer the question: How can an Environment, Community, Health Observatory Network support the integrative tools and processes required to improve understanding and response to the cumulative health impacts of resource development? The Network is informed by four regional cases across Canada where we employ a framework and an approach grounded in observation, “taking notice for action”, and collective learning. Sharing insights from the foundational phase of this five-year project, we reflect on the hidden and obvious challenges of working across scales, sectors, and sites, and the overlap of generative and uncomfortable entanglements associated with health and resource development. Yet, although intersectoral work addressing the cumulative impacts of resource extraction presents uncertainty and unresolved tensions, ultimately we argue that it is worth staying with the trouble