Starting from scratch: The primary hyperacidity theory of the cause of pyloric stenosis of infancy

The early observations of those who first described babies with pyloric stenosis (PS) are used as a backdrop for the development of the Inherited Primary Hyperacidity theory of cause. Those early truths, uncomplicated by modern technology, have acted as a springboard for pathogenesis. Hyperacidity, male predominance, family history, self-cure, enhanced appetite, and time-sensitive presentation were all well known to the early pioneers. Any system of pathogenesis must explain all these clinical features. The Inherited Primary Hyperacidity theory does this and is a credible explanation for all the clinical features established by these early pioneers. The evidence which supports a delay in maturation of the negative feedback between gastrin and gastric acidity is presented. Such a phenomenon further supports the Primary Hyperacidity theory.

Structural and Functional Coupling of Calcium-Activated BK Channels and Calcium-Permeable Channels Within Nanodomain Signaling Complexes

Biochemical and functional studies of ion channels have shown that many of these integral membrane proteins form macromolecular signaling complexes by physically associating with many other proteins. These macromolecular signaling complexes ensure specificity and proper rates of signal transduction. The large-conductance, Ca2+-activated K+ (BK) channel is dually activated by membrane depolarization and increases in intracellular free Ca2+ ([Ca2+]i). The activation of BK channels results in a large K+ efflux and, consequently, rapid membrane repolarization and closing of the voltage-dependent Ca2+-permeable channels to limit further increases in [Ca2+]i. Therefore, BK channel-mediated K+ signaling is a negative feedback regulator of both membrane potential and [Ca2+]i and plays important roles in many physiological processes and diseases. However, the BK channel formed by the pore-forming and voltage- and Ca2+-sensing α subunit alone requires high [Ca2+]i levels for channel activation under physiological voltage conditions. Thus, most native BK channels are believed to co-localize with Ca2+-permeable channels within nanodomains (a few tens of nanometers in distance) to detect high levels of [Ca2+]i around the open pores of Ca2+-permeable channels. Over the last two decades, advancement in research on the BK channel’s coupling with Ca2+-permeable channels including recent reports involving NMDA receptors demonstrate exemplary models of nanodomain structural and functional coupling among ion channels for efficient signal transduction and negative feedback regulation. We hereby review our current understanding regarding the structural and functional coupling of BK channels with different Ca2+-permeable channels.

Evolution of the repression mechanisms in circadian clocks

Background Circadian (daily) timekeeping is essential to the survival of many organisms. An integral part of all circadian timekeeping systems is negative feedback between an activator and repressor. However, the role of this feedback varies widely between lower and higher organisms. Results Here, we study repression mechanisms in the cyanobacterial and eukaryotic clocks through mathematical modeling and systems analysis. We find a common mathematical model that describes the mechanism by which organisms generate rhythms; however, transcription’s role in this has diverged. In cyanobacteria, protein sequestration and phosphorylation generate and regulate rhythms while transcription regulation keeps proteins in proper stoichiometric balance. Based on recent experimental work, we propose a repressor phospholock mechanism that models the negative feedback through transcription in clocks of higher organisms. Interestingly, this model, when coupled with activator phosphorylation, allows for oscillations over a wide range of protein stoichiometries, thereby reconciling the negative feedback mechanism in Neurospora with that in mammals and cyanobacteria. Conclusions Taken together, these results paint a picture of how circadian timekeeping may have evolved.

Different Effects of Supervisor Positive and Negative Feedback on Subordinate In-Role and Extra-Role Performance: The Moderating Role of Regulatory Focus

As an important tool for supervisors to intervene subordinates’ work and influence their performance, supervisor feedback has gradually become a new academic research hotspot. In this study, we build and verify a theoretical model to explore the different effects of supervisor positive and negative feedback on subordinate in-role and extra-role performance, and the moderating role of regulatory focus in these relationships. With data from pairing samples of 403 Chinese employees and their direct supervisors, the results indicate that supervisor positive feedback is positively related to subordinate in-role and extra-role performance. Supervisor negative feedback is positively related to subordinate in-role performance and negatively related to subordinate extra-role performance. Regulatory focus of subordinate can moderate the influence of supervisor positive feedback on subordinate in-role and extra-role performance, but it cannot moderate the influence of supervisor negative feedback on subordinate in-role and extra-role performance. That means when subordinates have promotion focus, the influence of supervisor positive feedback on their in-role performance and extra-role performance was stronger than those with prevention focus. These results further enrich the research on the relationship between supervisor feedback and subordinate performance, especially the different effects of positive and negative feedback from supervisor on subordinate with different regulatory focus. All conclusions from the analyses above not only further verify and develop some previous points on supervisor feedback and subordinate performance, but also derive certain management implications for promoting subordinate in-role and extra-role performance from the perspective of supervisor positive and negative feedback.

The role of social comparison and type of feedback on self-criticism in people with high levels of depressive symptoms

This research explores the relation between social comparison and self-criticism on a group of participants with elevated rates of depressive symptoms. In addition, the study investigated whether the type of feedback could moderate the relation between social comparison and self-criticism. The sample included 36 psychology students in the first year (N = 28 women, M age = 24.6, SD = 4.66) with high depressive symptoms. Results show that higher rates of negative social comparison are correlated with higher levels of self-criticism. Participants that received negative feedback reported an increase level of self-criticism compared to those from positive feedback condition. The type of feedback moderated the relation between social comparison and self-criticism. Our findings are discussed from the perspective of their practical implications for young adults experiencing high levels of depressive symptoms.

Pressure sensor chip utilizing electrical circuit of piezosensitive differential amplifier with negative feedback loop (PDA-NFL) for 5 kPa

High sensitive (S = 11.2 ± 1.8 mV/V/kPa with nonlinearity error 2KNL = 0.15 ± 0.09%/FS) small-sized (4.00x4.00 mm2) silicon pressure sensor chip utilizing new electrical circuit for microelectromechanical systems (MEMS) in the form of differential amplifier with negative feedback loop (PDA-NFL) for 5 kPa differential was developed. The advantages are demonstrated in the array of output characteristics, which prove the relevance of the presented development, relative to modern developments of pressure sensors with Wheatstone bridge electrical circuit for 5 kPa range.

Understanding the Shade Tolerance Responses Through Hints From Phytochrome A-Mediated Negative Feedback Regulation in Shade Avoiding Plants

Based on how plants respond to shade, we typically classify them into two groups: shade avoiding and shade tolerance plants. Under vegetative shade, the shade avoiding species induce a series of shade avoidance responses (SARs) to outgrow their competitors, while the shade tolerance species induce shade tolerance responses (STRs) to increase their survival rates under dense canopy. The molecular mechanism underlying the SARs has been extensively studied using the shade avoiding model plant Arabidopsis thaliana, while little is known about STRs. In Aarabidopsis, there is a PHYA-mediated negative feedback regulation that suppresses exaggerated SARs. Recent studies revealed that in shade tolerance Cardamine hirsuta plants, a hyperactive PHYA was responsible for suppressing shade-induced elongation growth. We propose that similar signaling components may be used by shade avoiding and shade tolerance plants, and different phenotypic outputs may result from differential regulation or altered dynamic properties of these signaling components. In this review, we summarized the role of PHYA and its downstream components in shade responses, which may provide insights into understanding how both types of plants respond to shade.