Split histidine kinases enable ultrasensitivity and bistability in two-component signaling networks

Bacteria sense and respond to their environment through signaling cascades generally referred to as two-component signaling networks. These networks comprise histidine kinases and their cognate response regulators. Histidine kinases have a number of biochemical activities: ATP binding, autophosphorylation, the ability to act as a phosphodonor for their response regulators, and in many cases the ability to catalyze the hydrolytic dephosphorylation of their response regulator. Here, we explore the functional role of “split kinases” where the ATP binding and phosphotransfer activities of a conventional histidine kinase are split onto two distinct proteins that form a complex. We find that this unusual configuration can enable ultrasensitivity and bistability in the signal-response relationship of the resulting system. These dynamics are displayed under a wide parameter range but only when specific biochemical requirements are met. We experimentally show that one of these requirements, namely segregation of the phosphatase activity predominantly onto the free form of one of the proteins making up the split kinase, is met in Rhodobacter sphaeroides. These findings indicate split kinases as a bacterial alternative for enabling ultrasensitivity and bistability in signaling networks. Genomic analyses reveal that up 1.7% of all identified histidine kinases have the potential to be split and bifunctional

Swinburnian Atonement and the Doctrine of Penal Substitution

This paper is a philosophical defense of the doctrine of penal substitution. I begin with a delineation of Richard Swinburne’s satisfaction-type theory of the atonement, exposing a weakness of it which motivates a renewed look at the theory of penal substitution. In explicating a theory of penal substitution, I contend that: (i) the execution of retributive punishment is morally justified in certain cases of deliberate wrongdoing; (ii) deliberate human sin against God constitutes such a case; and (iii) the transfer of the retributive punishment due sinners to Christ is morally coherent. Whatever else might be said for and against such a conception of the doctrine of the atonement, the plausibility of the theory presented here should give us pause in the often hasty rejection of the doctrine of penal substitutio

Modeling chemotaxis reveals the role of reversed phosphotransfer and a bi-functional kinase-phosphatase

Understanding how multiple signals are integrated in living cells to produce a balanced response is a major challenge in biology. Two-component signal transduction pathways, such as bacterial chemotaxis, comprise histidine protein kinases (HPKs) and response regulators (RRs). These are used to sense and respond to changes in the environment. Rhodobacter sphaeroides has a complex chemosensory network with two signaling clusters, each containing a HPK, CheA. Here we demonstrate, using a mathematical model, how the outputs of the two signaling clusters may be integrated. We use our mathematical model supported by experimental data to predict that: (1) the main RR controlling flagellar rotation, CheY6, aided by its specific phosphatase, the bifunctional kinase CheA3, acts as a phosphate sink for the other RRs; and (2) a phosphorelay pathway involving CheB2 connects the cytoplasmic cluster kinase CheA3 with the polar localised kinase CheA2, and allows CheA3-P to phosphorylate non-cognate chemotaxis RRs. These two mechanisms enable the bifunctional kinase/phosphatase activity of CheA3 to integrate and tune the sensory output of each signaling cluster to produce a balanced response. The signal integration mechanisms identified here may be widely used by other bacteria, since like R. sphaeroides, over 50% of chemotactic bacteria have multiple cheA homologues and need to integrate signals from different sources

The Sanctifying Work of the Holy Spirit: Revisiting Alston’s Interpersonal Model

Of the various loci of systematic theology that call for sustained philosophical investigation, the doctrine of sanctification stands out as a prime candidate.  In response to that call, William Alston developed three models of the sanctifying work of the Holy Spirit: the fiat model, the interpersonal model, and the sharing model.  In response to Alston’s argument for the sharing model, this paper offers grounds for a reconsideration of the interpersonal model.  We close with a discussion of some of the implications of one’s understanding of the transforming work of the Holy Spirit for practical Christian spirituality

National Institute of Neurological Disorders and Stroke (NINDS): Advances in understanding and treating neuropathy, 24–25 October 2006; Bethesda, Maryland

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75348/1/j.1529-8027.2008.00154.x.pd

Invitation to the Table Conversation: A Few Diverse Perspectives on Integration

This article represents an invitation to the integration table to several previously underrepresented perspectives within Christian psychology. The Judeo-Christian tradition and current views on scholarship and Christian faith compel us to extend hospitality to minority voices within integration, thereby enriching and challenging existing paradigms in the field. Contributors to this article, spanning areas of cultural, disciplinary, and theological diversity, provide suggestions for how their distinct voices can enhance future integrative efforts

Reform of High School Mathematics and Science and Opportunity to Learn

This brief concerns the nature of the high school mathematics and science curriculum in the United States. It draws from a large study which documented instructional practices and content using novel methodologies. This research approach is a promising step toward the development of indicators of opportunity to learn. The study also provides encouraging news about the effects of increased standards in math and science - they did not result in a watering down of the curriculum. However, practice in the schools studied is a far cry from the ambitious goals for math and science instruction now being developed by the profession

UNLV College of Education Multicultural & Diversity Newsletter

A newsletter discussing a variety of topics dealing with multicultural topics and diversity in education

Behavioral Responses of Pacific Lamprey to Alarm Cues

Pacific lamprey (Entosphenus tridentatus), an anadromous ectoparasite, faces several challenges during adult migration to spawning grounds. Developingmethods to address these challenges is critical to the success of ongoing conservation efforts. The challenges are diverse, and include anthropogenic alterations to the ecosystem resulting in loss of habitat, impassable barriers such as dams, climate change impacts, and altered predator fields. We conducted a behavioral study to understand how adult migrating Pacific lamprey respond to potential alarm cues: White Sturgeon (Acipenser transmontanus), human saliva, decayed Pacific lamprey, and river otter (Lontra canadensis). Research has shown that some species of lamprey can be guided to a location using odors and similar cues may be useful as a management tool for Pacific lamprey. Experiments were conducted over 2 nights and measured the number of entries (count) and duration of time spent (occupancy) by adult lamprey in each arm of a two-choice maze. During the first night, no odor was added to test for selection bias between arms. During the second night odor was added to one arm of the maze. Contrary to expectations, lamprey were significantly attracted to the river otter odor in both count and occupancy. No significant differences were found in the response of lamprey to the other three odors. Results from this study indicate that Pacific lamprey do respond to some odors; however, additional tests are necessary to better identify the types of odors and concentrations that elicit a repeatable response