Ca2+ Influx and Tyrosine Kinases Trigger Bordetella Adenylate Cyclase Toxin (ACT) Endocytosis. Cell Physiology and Expression of the CD11b/CD18 Integrin Major Determinants of the Entry Route

Humans infected with Bordetella pertussis, the whooping cough bacterium, show evidences of impaired host defenses. This pathogenic bacterium produces a unique adenylate cyclase toxin (ACT) which enters human phagocytes and catalyzes the unregulated formation of cAMP, hampering important bactericidal functions of these immune cells that eventually cause cell death by apoptosis and/or necrosis. Additionally, ACT permeabilizes cells through pore formation in the target cell membrane. Recently, we demonstrated that ACT is internalised into macrophages together with other membrane components, such as the integrin CD11b/CD18 (CR3), its receptor in these immune cells, and GM1. The goal of this study was to determine whether ACT uptake is restricted to receptor-bearing macrophages or on the contrary may also take place into cells devoid of receptor and gain more insights on the signalling involved. Here, we show that ACT is rapidly eliminated from the cell membrane of either CR3-positive as negative cells, though through different entry routes, which depends in part, on the target cell physiology and characteristics. ACT-induced Ca2+ influx and activation of non-receptor Tyr kinases into the target cell appear to be common master denominators in the different endocytic strategies activated by this toxin. Very importantly, we show that, upon incubation with ACT, target cells are capable of repairing the cell membrane, which suggests the mounting of an anti-toxin cell repair-response, very likely involving the toxin elimination from the cell surface.

The Voting Rights Act, Shelby County, and Redistricting: Improving Estimates of Racially Polarized Voting in a Multiple-Election Context

The Supreme Court’s decision in Shelby County has severely limited the power of the Voting Rights Act. I argue that Congressional attempts to pass a new coverage formula are unlikely to gain the necessary Republican support. Instead, I propose a new strategy that takes a “carrot and stick” approach. As the stick, I suggest amending Section 3 to eliminate the need to prove that discrimination was intentional. For the carrot, I envision a competitive grant program similar to the highly successful Race to the Top education grants. I argue that this plan could pass the currently divided Congress.

Without Congressional action, Section 2 is more important than ever before. A successful Section 2 suit requires evidence that voting in the jurisdiction is racially polarized. Accurately and objectively assessing the level of polarization has been and continues to be a challenge for experts. Existing ecological inference methods require estimating polarization levels in individual elections. This is a problem because the Courts want to see a history of polarization across elections.

I propose a new 2-step method to estimate racially polarized voting in a multi-election context. The procedure builds upon the Rosen, Jiang, King, and Tanner (2001) multinomial-Dirichlet model. After obtaining election-specific estimates, I suggest regressing those results on election-specific variables, namely candidate quality, incumbency, and ethnicity of the minority candidate of choice. This allows researchers to estimate the baseline level of support for candidates of choice and test whether the ethnicity of the candidates affected how voters cast their ballots.

On the economics of the "meeting competition defense" under the Robinson-Patman Act

Documento de trabajo

The Great Whales: History and Status of Six Species Listed as Endangered Under the U.S. Endangered Species Act of 1973

In the history of whaling from prehistoric to modern times, the large whales, sometimes called the “great whales,” were hunted most heavily owing in part to their corresponding value in oil, meat, and baleen. Regional populations of North Atlantic right whales, Eubalaena glacialis glacialis, were already decimated by 1700, and the North Atlantic gray whale, Eschrichtius robustus, was hunted to extinction by the early 1700’s (Mitchell and Mead1).

The Threatened Status of Steller Sea Lions, Eumetopias jubatus, under the Endangered Species Act: Effects on Alaska Groundfish Fisheries Management

In April 1990, the Steller sea lion, Eumetopias jubatus, was listed as threatened under the U.S. Endangered Species Act by emergency action. Competitive interactions with the billion-dollar Alaska commercial groundfish fisheries have been suggested as one of the possible contributing factors to the Steller sea lion population decline. Since the listing, fisheries managers have attempted to address the potential impacts of the groundfish fisheries on Steller sea lion recovery. In this paper, we review pertinent Federal legislation, biological information on the Steller sea lion decline, changes in the Alaska trawl fishery for walleye pollock, Theragra chalcogramma, since the late 1970's, andpossible interactions between fisheries and sea lions. Using three cases, we illustrate how the listing of Steller sea lions has affected Alaska groundfish fisheries through: I) actions taken at the time of listing designed to limit the potential for directhuman-related sea lion mortality, 2) actions addressing spatial and temporal separation of fisheries from sea lions, and 3) introduction of risk-adverse stock assessment methodologies and Steller sea lion conservation considerations directly in the annual quota-setting process. This discussion shows some of the ways that North Pacific groundfish resource managers have begun to explicitly consider the conservation ofmarine mammal and other nontarget species.

Pacific Salmon, Oncorhynchus spp., and the Definition of "Species" Under the Endangered Species Act

For purposes ofthe Endangered Species Act (ESA), a "species" is defined to include "any distinct population segment of any species of vertebrate fish or wildlife which interbreeds when mature. "Federal agencies charged with carrying out the provisions of the ESA have struggled for over a decade to develop a consistent approach for interpreting the term "distinct population segment." This paper outlines such an approach and explains in some detail how it can be applied to ESA evaluations of anadromous Pacific salmonids. The following definition is proposed: A population (or group of populations) will be considered "distinct" (and hence a "species ")for purposes of the ESA if it represents an evolutionarily significant unit (ESU) of the biological species. A population must satisfy two criteria to be considered an ESU: 1) It must be substantially reproductively isolated from other conspecific population units, and 2) It must represent an important component in the evolutionary legacy of the species. Isolation does not have to be absolute, but it must be strong enough to permit evolutionarily important differences to accrue in different population units. The second criterion would be met if the population contributes substantially to the ecological/genetic diversity of the species as a whole. Insights into the extent of reproductive isolation can be provided by movements of tagged fish, natural recolonization rates observed in other populations, measurements of genetic differences between populations, and evaluations of the efficacy of natural barriers. Each of these methods has its limitations. Identification of physical barriers to genetic exchange can help define the geographic extent of distinct populations, but reliance on physical features alone can be misleading in the absence of supporting biological information. Physical tags provide information about the movements of individual fish but not the genetic consequences of migration. Furthermore, measurements ofc urrent straying or recolonization rates provide no direct information about the magnitude or consistency of such rates in the past. In this respect, data from protein electrophoresis or DNA analyses can be very useful because they reflect levels of gene flow that have occurred over evolutionary time scales. The best strategy is to use all available lines of evidence for or against reproductive isolation, recognizing the limitations of each and taking advantage of the often complementary nature of the different types of information. If available evidence indicates significant reproductive isolation, the next step is to determine whether the population in question is of substantial ecological/genetic importance to the species as a whole. In other words, if the population became extinct, would this event represent a significant loss to the ecological/genetic diversity of thes pecies? In making this determination, the following questions are relevant: 1) Is the population genetically distinct from other conspecific populations? 2) Does the population occupy unusual or distinctive habitat? 3) Does the population show evidence of unusual or distinctive adaptation to its environment? Several types of information are useful in addressing these questions. Again, the strengths and limitations of each should be kept in mind in making the evaluation. Phenotypic/life-history traits such as size, fecundity, and age and time of spawning may reflect local adaptations of evolutionary importance, but interpretation of these traits is complicated by their sensitivity to environmental conditions. Data from protein electrophoresis or DNA analyses provide valuable insight into theprocessofgenetic differentiation among populations but little direct information regarding the extent of adaptive genetic differences. Habitat differences suggest the possibility for local adaptations but do not prove that such adaptations exist. The framework suggested here provides a focal point for accomplishing the majorgoal of the Act-to conserve the genetic diversity of species and the ecosystems they inhabit. At the same time, it allows discretion in the listing of populations by requiring that they represent units of real evolutionary significance to the species. Further, this framework provides a means of addressing several issues of particular concern for Pacific salmon, including anadromous/nonanadromous population segments, differences in run-timing, groups of populations, introduced populations, and the role of hatchery fish.

Human muscle spindles act as forward sensory models.

Modern theories of motor control incorporate forward models that combine sensory information and motor commands to predict future sensory states. Such models circumvent unavoidable neural delays associated with on-line feedback control. Here we show that signals in human muscle spindle afferents during unconstrained wrist and finger movements predict future kinematic states of their parent muscle. Specifically, we show that the discharges of type Ia afferents are best correlated with the velocity of length changes in their parent muscles approximately 100-160 ms in the future and that their discharges vary depending on motor sequences in a way that cannot be explained by the state of their parent muscle alone. We therefore conclude that muscle spindles can act as "forward sensory models": they are affected both by the current state of their parent muscle and by efferent (fusimotor) control, and their discharges represent future kinematic states. If this conjecture is correct, then sensorimotor learning implies learning how to control not only the skeletal muscles but also the fusimotor system.

Bycatch provisions in the reauthorized Magnuson-Stevens Act

Bycatch can harm marine ecosystems, reduce biodiversity, lead to injury or mortality of protected species, and have severe economic implications for fisheries. On 12 January 2007, President George W. Bush signed the Magnuson-Stevens Fishery Conservation and Management Reauthorization Act of 2006 (MSRA). The MSRA required the U.S. Secretary of Commerce (Secretary) to establish a Bycatch Reduction Engineering Program (BREP) to develop technological devices and other conservation engineering changes designed to minimize bycatch, seabird interactions, bycatch mortality, and post-release mortality in Federally managed fisheries. The MSRA also required the Secretary to identify nations whose vessels are engaged in the bycatch of protected living marine resources (PLMR’s) under specified circumstances and to certify that these nations have 1) adopted regulatory programs for PLMR’s that are comparable to U.S. programs, taking into account different conditions, and 2) established management plans for PLMR’s that assist in the collection of data to support assessments and conservation of these resources. If a nation fails to take sufficient corrective action and does not receive a positive certification, fishing products from that country may be subject to import prohibitions into the United States. The BREP has made significant progress to develop technological devices and other conservation engineering designed to minimize bycatch, including improvements to bycatch reduction devices and turtle excluder devices in Atlantic and Gulf of Mexico trawl fisheries, gillnets in Northeast fisheries, and trawls in Alaska and Pacific Northwest fisheries. In addition, the international provisions of the MSRA have provided an innovative tool through which the United States can address bycatch by foreign nations. However, the inability of the National Marine Fisheries Service to identify nations whose vessels are engaged in the bycatch of PLMR’s to date will require the development of additional approaches to meet this mandate.

Motor coordination: when two have to act as one.

Trying to pass someone walking toward you in a narrow corridor is a familiar example of a two-person motor game that requires coordination. In this study, we investigate coordination in sensorimotor tasks that correspond to classic coordination games with multiple Nash equilibria, such as "choosing sides," "stag hunt," "chicken," and "battle of sexes". In these tasks, subjects made reaching movements reflecting their continuously evolving "decisions" while they received a continuous payoff in the form of a resistive force counteracting their movements. Successful coordination required two subjects to "choose" the same Nash equilibrium in this force-payoff landscape within a single reach. We found that on the majority of trials coordination was achieved. Compared to the proportion of trials in which miscoordination occurred, successful coordination was characterized by several distinct features: an increased mutual information between the players' movement endpoints, an increased joint entropy during the movements, and by differences in the timing of the players' responses. Moreover, we found that the probability of successful coordination depends on the players' initial distance from the Nash equilibria. Our results suggest that two-person coordination arises naturally in motor interactions and is facilitated by favorable initial positions, stereotypical motor pattern, and differences in response times.