Health Education across Academic Disciplines (HEAAD): A Tool to Help Students Think Critically about the Risks of Excessive Cell Phone Use

Background and Purpose: Studies have shown that teens who hypertext are at a higher risk to engage in other health risk behaviors including binge drinking, tobacco use, illicit drug use, partaking in physical fights, engaging in risky sexual behavior, and driving distracted. Interventions addressing excessive use of mobile devices have mainly focused on mobile phone use while driving. The aim is to describe the Health Education Across Academic Disciplines (HEAAD) teaching tool and implementation, which may help to educate and raise awareness of the risks associated with excessive cell phone use among adolescents and young adults. Educational Teaching Tool: HEAAD includes introductory activities ranging from identifying risks related to excessive cell phone use to follow-up interactive activities with examples applied across academic disciplines other than health. HEAAD targets students in grades nine through twelve and can be adapted to the college population for freshmen and sophomores enrolled in personal health and wellness classes and/or other health orientation and first year experience classes. Conclusion: HEAAD intends to engage students in practicing decision-making skills related to excessive cell phone use, which may be applicable to their lives. Pilot testing of HEAAD is recommended to determine its effectiveness and potential

Perceptions of diversity, equity, and inclusion within undergraduate curriculum and university: A qualitative study

Objective Diversity, equity, and inclusion (DEI) efforts are important at university campuses, especially preparing students for the workforce. This study aimed to identify perceptions of DEI among seniors related to their major curriculum and at the university. Participants In Spring 2021, 101 graduating seniors, who are future health professionals, completed an online survey. Methods Open-ended and multiple-choice survey items were analyzed. Thematic coding for open-ended questions and SPSS was used for the quantitative analysis. Results Analyses revealed the university kept students informed of DEI activities; however, more could be done. In the department, participants reported that classes focused on DEI activities; however, some faculty entered classrooms without evaluating their own implicit biases. Future suggestions include creating a DEI-focused course and increasing faculty and student representation from underrepresented backgrounds. Conclusions Findings from this study can be used to inform DEI-related courses as well as faculty hiring and student recruitment guidelines

Hyperledger Fabric: A Distributed Operating System for Permissioned Blockchains

Fabric is a modular and extensible open-source system for deploying and operating permissioned blockchains and one of the Hyperledger projects hosted by the Linux Foundation (www.hyperledger.org). Fabric is the first truly extensible blockchain system for running distributed applications. It supports modular consensus protocols, which allows the system to be tailored to particular use cases and trust models. Fabric is also the first blockchain system that runs distributed applications written in standard, general-purpose programming languages, without systemic dependency on a native cryptocurrency. This stands in sharp contrast to existing blockchain platforms that require "smart-contracts" to be written in domain-specific languages or rely on a cryptocurrency. Fabric realizes the permissioned model using a portable notion of membership, which may be integrated with industry-standard identity management. To support such flexibility, Fabric introduces an entirely novel blockchain design and revamps the way blockchains cope with non-determinism, resource exhaustion, and performance attacks. This paper describes Fabric, its architecture, the rationale behind various design decisions, its most prominent implementation aspects, as well as its distributed application programming model. We further evaluate Fabric by implementing and benchmarking a Bitcoin-inspired digital currency. We show that Fabric achieves end-to-end throughput of more than 3500 transactions per second in certain popular deployment configurations, with sub-second latency, scaling well to over 100 peers.Comment: Appears in proceedings of EuroSys 2018 conferenc

Signaling interactions in the adrenal cortex

The major physiological stimuli of aldosterone secretion are angiotensin II (AII) and extracellular K+ whereas cortisol production is primarily regulated by corticotrophin (ACTH) in fasciculata cells. AII triggers Ca2+ release from internal stores that is followed by store-operated and voltage-dependent Ca2+ entry whereas K+-evoked depolarisation activates voltage-dependent Ca2+ channels. ACTH acts primarily through the formation of cAMP and subsequent protein phosphorylation by protein kinase A. Both Ca2+ and cAMP facilitate the transfer of cholesterol to mitochondrial inner membrane. The cytosolic Ca2+ signal is transferred into the mitochondrial matrix and enhances pyridine nucleotide reduction. Increased formation of NADH results in increased ATP production whereas that of NADPH supports steroid production. In reality, the control of adrenocortical function is a lot more sophisticated with second messengers crosstalking and mutually modifying each other’s pathways. Cytosolic Ca2+ and cGMP are both capable of modifying cAMP metabolism whilst cAMP may enhance Ca2+ release and voltage-activated Ca2+ channel activity. Besides, mitochondrial Ca2+ signal brings about cAMP formation within the organelle and this further enhances aldosterone production. Maintained aldosterone and cortisol secretion are optimized by the concurrent actions of Ca2+ and cAMP, as exemplified by the apparent synergism of Ca2+ influx (inducing cAMP formation) and Ca2+ release during response to AII. Thus, cross-actions of parallel signal transducing pathways are not mere intracellular curiosities but rather substantial phenomena which fine-tune the biological response. Our review focuses on these functionally relevant interactions between the Ca2+ and the cyclic nucleotide signal transducing pathways hitherto described in the adrenal cortex

Detecting Clusters of Mutations

Positive selection for protein function can lead to multiple mutations within a small stretch of DNA, i.e., to a cluster of mutations. Recently, Wagner proposed a method to detect such mutation clusters. His method, however, did not take into account that residues with high solvent accessibility are inherently more variable than residues with low solvent accessibility. Here, we propose a new algorithm to detect clustered evolution. Our algorithm controls for different substitution probabilities at buried and exposed sites in the tertiary protein structure, and uses random permutations to calculate accurate P values for inferred clusters. We apply the algorithm to genomes of bacteria, fly, and mammals, and find several clusters of mutations in functionally important regions of proteins. Surprisingly, clustered evolution is a relatively rare phenomenon. Only between 2% and 10% of the genes we analyze contain a statistically significant mutation cluster. We also find that not controlling for solvent accessibility leads to an excess of clusters in terminal and solvent-exposed regions of proteins. Our algorithm provides a novel method to identify functionally relevant divergence between groups of species. Moreover, it could also be useful to detect artifacts in automatically assembled genomes

ACTH Induces Cav3.2 Current and mRNA by cAMP-dependent and cAMP-independent Mechanisms*

Bovine adrenal zona fasciculata (AZF) cells express Cav3.2 T-type Ca2+ channels that function pivotally in adrenocorticotropic hormone (ACTH)-stimulated cortisol secretion. The regulation of Cav3.2 expression in AZF cells by ACTH, cAMP analogs, and their metabolites was studied using Northern blot and patch clamp recording. Exposing AZF cells to ACTH for 3–6 days markedly enhanced the expression of Cav3.2 current. The increase in Cav3.2 current was preceded by an increase in corresponding CACNA1H mRNA. O-Nitrophenyl,sulfenyl-adrenocorticotropin, which produces a minimal increase in cAMP, also enhanced Cav3.2 current. cAMP analogs, including 8-bromoadenosine cAMP (600 μm) and 6-benzoyladenosine cAMP (300 μm) induced CACNA1H mRNA, but not Cav3.2 current. In contrast, 8-(4-chlorophenylthio) (8CPT)-cAMP (10–50 μm) enhanced CACNA1H mRNA and Cav3.2 current, whereas nonhydrolyzable Sp-8CPT-cAMP failed to increase either Cav3.2 current or mRNA. Metabolites of 8CPT-cAMP, including 8CPT-adenosine and 8CPT-adenine, increased Cav3.2 current and mRNA with a potency and effectiveness similar to the parent compound. The Epac activator 8CPT-2′-O-methyl-cAMP and its metabolites 8CPT-2′-OMe-5′-AMP and 8CPT-2′-O-methyl-adenosine increased CACNA1H mRNA and Cav3.2 current; Sp-8CPT-2′-O-methyl-cAMP increased neither Cav3.2 current nor mRNA. These results reveal an interesting dichotomy between ACTH and cAMP with regard to regulation of CACNA1H mRNA and Ca2+ current. Specifically, ACTH induces expression of CACNA1H mRNA and Cav3.2 current in AZF cells by mechanisms that depend at most only partly on cAMP. In contrast, cAMP enhances expression of CACNA1H mRNA but not the corresponding Ca2+ current. Surprisingly, chlorophenylthio-cAMP analogs stimulate the expression of Cav3.2 current indirectly through metabolites. ACTH and the metabolites may induce Cav3.2 expression by the same, unidentified mechanism

cAMP Analogs and Their Metabolites Enhance TREK-1 mRNA and K+ Current Expression in Adrenocortical CellsS⃞

bTREK-1 K+ channels set the resting membrane potential of bovine adrenal zona fasciculata (AZF) cells and function pivotally in the physiology of cortisol secretion. Adrenocorticotropic hormone controls the function and expression of bTREK-1 channels through signaling mechanisms that may involve cAMP and downstream effectors including protein kinase A (PKA) and exchange protein 2 directly activated by cAMP (Epac2). Using patch-clamp and Northern blot analysis, we explored the regulation of bTREK-1 mRNA and K+ current expression by cAMP analogs and several of their putative metabolites in bovine AZF cells. At concentrations sufficient to activate both PKA and Epac2, 8-bromoadenosine-cAMP enhanced the expression of both bTREK-1 mRNA and K+ current. N6-Benzoyladenosine-cAMP, which activates PKA but not Epac, also enhanced the expression of bTREK-1 mRNA and K+ current measured at times from 24 to 96 h. An Epac-selective cAMP analog, 8-(4-chlorophenylthio)-2′-O-methyl-cAMP (8CPT-2′-OMe-cAMP), potently stimulated bTREK-1 mRNA and K+ current expression, whereas the nonhydrolyzable Epac activator 8-(4-chlorophenylthio)-2′-O-methyl-cAMP, Sp-isomer was ineffective. Metabolites of 8CPT-2′-OMe-cAMP, including 8-(4-chlorophenylthio)-2′-O-methyladenosine-5′-O-monophosphate and 8CPT-2′-OMe-adenosine, promoted the expression of bTREK-1 transcripts and ion current with a temporal pattern, potency, and effectiveness resembling that of the parent compound. Likewise, at low concentrations, 8-(4-chlorophenylthio)-cAMP (8CPT-cAMP; 30 μM) but not its nonhydrolyzable analog 8-(4-chlorophenylthio)-cAMP, Sp-isomer, enhanced the expression of bTREK-1 mRNA and current. 8CPT-cAMP metabolites, including 8CPT-adenosine and 8CPT-adenine, also increased bTREK-1 expression. These results indicate that cAMP increases the expression of bTREK-1 mRNA and K+ current through a cAMP-dependent but Epac2-independent mechanism. They further demonstrate that one or more metabolites of 8-(4-chlorophenylthio)-cAMP analogs potently stimulate bTREK-1 expression by activation of a novel cAMP-independent mechanism. These findings raise significant questions regarding the specificity of 8-(4-chlorophenylthio)-cAMP analogs as cAMP mimetics

Thermosensitivity of the two-pore domain K(+) channels TREK-2 and TRAAK

TREK-1, TREK-2 and TRAAK are members of the two-pore domain K(+) (K(2P)) channel family and are activated by membrane stretch and free fatty acids. TREK-1 has been shown to be sensitive to temperature in expression systems. We studied the temperature-sensitivity of TREK-2 and TRAAK in COS-7 cells and in neuronal cells. In transfected COS-7 cells, TREK-2 and TRAAK whole-cell currents increased ∼20-fold as the bath temperature was raised from 24°C to 42°C. Similarly, in cell-attached patches of COS-7 cells, channel activity was very low, but increased progressively as the bath temperature was raised from 24°C to 42°C. The thresholds for activation of TREK-2 and TRAAK were ∼25°C and ∼31°C, respectively. Other K(2P) channels such as TASK-3 and TRESK-2 were not significantly affected by an increase in temperature from 24°C to 37°C. When the C-terminus of TREK-2 was replaced with that of TASK-3, its sensitivity to free fatty acids and protons was abolished, but the mutant could still be activated by heat. At 37°C, TREK-1, TREK-2 and TRAAK were sensitive to arachidonic acid, pH and membrane stretch in both cell-attached and inside-out patches. In cerebellar granule and dorsal root ganglion neurones, TREK-1, TREK-2 and TRAAK were generally inactive in the cell-attached state at 24°C, but became very active at 37°C. In cell-attached patches of ventricular myocytes, TREK-1 was also normally closed at 24°C, but was active at 37°C. These results show that TREK-2 and TRAAK are also temperature-sensitive channels, are active at physiological body temperature, and therefore would contribute to the background K(+) conductance and regulate cell excitability in response to various physical and chemical stimuli