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This study addresses African-Americans' retirement readiness and the factors that contribute to African Americans being prepared or not prepared for retirement. Specifically, this study explores the relationship between educated African-Americans' financial literacy and their retirement readiness. To analyze this relationship, a binary logistic regression model was fitted to primary data collected from graduates, professors, and business professionals associated with a liberal arts university located in the southeastern USA. The researchers found that educated African-Americans who are more financially literate are more likely to be ready for retirement versus educated African-Americans who are less financially literate. This finding suggests that education does not equate to financial literacy. Moreover, millennials are more likely to be prepared for retirement compared to other age groups, and those who are single and those who do not work full time are less likely to be prepared for retirement., Author(s): John H. Young [sup.1] , Crystal R. Hudson [sup.1] , Edward L. Davis [sup.2] Author Affiliations: (1) Finance Department, Clark Atlanta University, 0000 0001 2224 3669, grid.254275.3, , 223 [...]

Human immunodeficiency virus (HIV) has a small genome and therefore relies heavily on the host cellular machinery to replicate. Identifying which host proteins and complexes come into physical contact with the viral proteins is crucial for a comprehensive understanding of how HIV rewires the host's cellular machinery during the course of infection. Here we report the use of affinity tagging and purification mass spectrometry (1-3) to determine systematically the physical interactions of all 18 HIV-1 proteins and polyproteins with host proteins in two different human cell lines (HEK293 and Jurkat). Using a quantitative scoring system that we call MiST, we identified with high confidence 497 HIV-human protein-protein interactions involving 435 individual human proteins, with ~40% of the interactions being identified in both cell types. We found that the host proteins hijacked by HIV, especially those found interacting in both cell types, are highly conserved across primates. We uncovered a number of host complexes targeted by viral proteins, including the finding that HIV protease cleaves eIF3d, a subunit of eukaryotic translation initiation factor 3. This host protein is one of eleven identified in this analysis that act to inhibit HIV replication. This data set facilitates a more comprehensive and detailed understanding of how the host machinery is manipulated during the course of HIV infection., A map of the physical interactions between proteins within a particular system is necessary for studying the molecular mechanisms that underlie the system. The analysis of protein-protein interactions (PPIs) has [...]

Abstract--In response to petitions to list the black-tailed prairie dog (BTPD, Cvnomys ludovicianus Ord) as threatened under the Endangered Species Act, an inventory of the BTPD in Texas was undertaken. [...]

Both treatment of disease and basic studies of complex tissues can benefit from directing viral vector infection to specific cell types. We have used a unique cell targeting method to direct viral vector transduction to cerebral cortical neurons expressing the neuregulin (NRG) receptor ErbB4; both NRG and ErbB4 have been implicated in schizophrenia, and ErbB4 expression in cerebral cortex is known to be restricted to inhibitory neurons. We find that a bridge protein composed of the avian viral receptor TVB fused to NRG, along with EnvB-psuedotyped virus, is able to direct infection selectively to ErbB4-expressing inhibitory cortical neurons in vivo. Interestingly, although ErbB4 is expressed in a broad range of cortical inhibitory cell types, NRG-dependent infection is restricted to a more selective subset of inhibitory cell types. These results demonstrate a tool that can be used for further studies of NRG and ErbB receptors in brain circuits and demonstrate the feasibility for further development of related bridge proteins to target gene expression to other specific cell types in complex tissues. neuregulin | rabies virus | avian virus receptor for subgroup B | lentivirus | EnvB doi/ 10.1073/pnas.1006233107

The present study examined the effects of adding leucine to pre and postexercise carbohydrate beverages on selected markers of muscle damage, delayed-onset muscle soreness (DOMS), and squat performance for up to 72 hours after lower-body resistance training. Seventeen resistance trained men (mean [+ or -] SD age 22.9 [+ or -] 2.9 years) and 3 resistance trained women (mean [+ or -] SD age 21.6 [+ or -] 2.6 years) performed 6 sets of squats to fatigue using 75[degrees]/o of the 1 repetition maximum. Each subject consumed a carbohydrate beverage 30 minutes before and immediately after exercise with or without the addition of 22.5 mg x [kg.sup.-1] (45 mg x [kg.sup.-1] total) of leucine in a randomized, double-blind fashion. Serum creatine kinase (CK), lactate dehydrogenase (LDH), and DOMS were analyzed immediately before (TIME1), 24 (TIME2), 48 (TIME3), and 72 (TIME4) hours after exercise. The subjects repeated the squat protocol at TIME4 to test recovery. No differences were observed between groups for squat performance, defined as the total number of repetitions performed during 6 sets of squats, for both TIME1 and TIME4. The addition of leucine did not significantly decrease CK and LDH activity or DOMS. These results suggested that adding leucine to carbohydrate beverages did not affect acute muscle recovery and squat performance during both initial testing and during a subsequent exercise bout 72 hours later in resistance trained subjects. KEY WORDS amino acids, eccentric, delayed-onset muscle soreness

The vertebrate heart is formed from diverse embryonic territories, including the first and second heart fields. The second heart field (SHF) gives rise to the right ventricle and outflow tract, yet its evolutionary origins are unclear. We found that heart progenitor ceils of the simple chordate Ciona intestinalis also generate precursors of the atrial siphon muscles (ASMs). These precursors express Islet and Tbx1/10, evocative of the splanchnic mesoderm that produces the lower jaw muscles and SHF of vertebrates. Evidence is presented that the transcription factor COE is a critical determinant of ASM fate. We propose that the last common ancestor of tunicates and vertebrates possessed multipotent cardiopharyngeal muscle precursors, and that their reallocation might have contributed to the emergence of the SHF. 10.l126/science.1190181

Many introductory physical geography textbooks use the term 'heat' in ways that reflect usage of the word in physics and chemistry textbooks prior to the late 1960s. It is now generally accepted by the physics and chemistry communities that heat is energy that is transferred between a system and its environment as a consequence of a temperature difference across a system boundary. Once the energy transfer is accomplished, the energy is no longer heat. Therefore heat cannot be stored. Although the greenhouse effect results in heat transfer through radiation, it is incorrect to state that heat is trapped, stored, contained or held in the atmosphere.

Byline: Robert D. Latzman (1), Kim L. Gratz (1), John Young (2), Laurie J. Heiden (3), John D. Damon (3), Terry L. Hight (3) Keywords: Self-injury; Self-harm; Adolescents; Gender; Race; School-level Abstract: Despite the clinical relevance of self-injurious thoughts and behaviors (SITB) among youth, little is known about the subset of youth most at-risk for SITB. This study examined the moderating roles of gender, racial/ethnic background, and school-level (and their interactions) on rates of SITB within a large (N = 2638, 52.2% female), ethnically-diverse sample of middle- and high-school youth in a relatively poor and underserved area of the Southern United States. Extending extant research in this area, findings indicated a significant interaction between gender and race for self-injurious behaviors, with African--American boys reporting higher rates than all other groups. Findings also indicated significant interactions between school-level and both gender and race for self-injurious thoughts. Whereas comparable levels of self-injurious thoughts were reported across middle- and high-schools for girls and African--American youth, the frequency of these thoughts was higher among both boys and White students in high-school (vs. middle-school). Results highlight the need for further research on SITB among diverse youth in underserved areas. Author Affiliation: (1) Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 North State St., Jackson, MS, 39216, USA (2) Department of Psychology, University of Mississippi, University, MS, USA (3) Mississippi Children's Home Services--CARES School, Jackson, MS, USA Article History: Registration Date: 01/10/2009 Received Date: 30/07/2009 Accepted Date: 01/10/2009 Online Date: 16/10/2009

Influenza A virus is an RNA virus that encodes up to 11 proteins and this small coding capacity demands that the virus use the host cellular machinery for many aspects of its life cycle (1). Knowledge of these host cell requirements not only informs us of the molecular pathways exploited by the virus but also provides further targets that could be pursued for antiviral drug development. Here we use an integrative systems approach, based on genome-wide RNA interference screening, to identify 295 cellular cofactors required for early-stage influenza virus replication. Within this group, those involved in kinase-regulated signalling, ubiquitination and phosphatase activity are the most highly enriched, and 181 factors assemble into a highly significant host-pathogen interaction network. Moreover, 219 of the 295 factors were confirmed to be required for efficient wild-type influenza virus growth, and further analysis of a subset of genes showed 23 factors necessary for viral entry, including members of the vacuolar ATPase (vATPase) and COPI-protein families, fibroblast growth factor receptor (FGFR) proteins, and glycogen synthase kinase 3 (GSK3)-β. Furthermore, 10 proteins were confirmed to be involved in post-entry steps of influenza virus replication. These include nuclear import components, proteases, and the calcium/ calmodulin-dependent protein kinase (CaM kinase) IIβ (CAMK2B). Notably, growth of swine-origin H1N1 influenza virus is also dependent on the identified host factors, and we show that small molecule inhibitors of several factors, including vATPase and CAMK2B, antagonize influenza virus replication., Influenza viruses are a major cause of morbidity and mortality, and influenza A viruses in particular have the propensity to cause pandemic outbreaks such as occurred in 1918, 1957, 1968 [...]

Worry is a central component to anxiety, and intolerance of uncertainty (IU) is an identified factor contributing to worry. It has been noted that parenting behaviors play a role in the anxious development of youth, specifically with regard to these constructs. We sought to examine the relationship of parenting behaviors in the development of IU. Internet-based assessments of current anxiety, worry, and depression were correlated with retrospective reports of parental behavior. It was found that IU was significantly correlated with worry, anxiety, and depression. Additionally, in several mediation analyses, it was noted that IU was a mediator between perceived anxious rearing and both worry and anxiety, but not depression. The implications of these results and internet-based methodology are discussed, particularly in terms of the novel findings from IU mediation analyses. Keywords Anxiety * Worry * Parenting * Uncertainty DOI 10.1007/s10826-009-9269-7

Reuven Brenner ('The Rule of Law and the Wealth of Nations,' August/September, 2009) provides a careful analysis of the roles that need to be played by both the financial sector [...]

Insect wings are complex structures that deform dramatically in flight. We analyzed the aerodynamic consequences of wing deformation in locusts using a three-dimensional computational fluid dynamics simulation based on detailed wing kinematics. We validated the simulation against smoke visualizations and digital particle image velocimetry on real locusts. We then used the validated model to explore the effects of wing topography and deformation, first by removing camber while keeping the same time-varying twist distribution, and second by removing camber and spanwise twist. The full-fidelity model achieved greater power economy than the uncambered model, which performed better than the untwisted model, showing that the details of insect wing topography and deformation are important aerodynamically. Such details are likely to be important in engineering applications of flapping flight.

It is the objective of this paper to review recent developments in the understanding and prediction of flapping-wing aerodynamics. To this end, several flapping-wing configurations are considered. First, the problem of single flapping wings is treated with special emphasis on the dependence of thrust, lift, and propulsive efficiency on flapping mode, amplitude, frequency, and wing shape. Second, the problem of hovering flight is studied for single flapping wings. Third, the aerodynamic phenomena and benefits produced by the flapping-wing interactions on tandem wings or biplane configurations are discussed. Such interactions occur on dragonflies or on a recently developed micro air vehicle. The currently available two- and three-dimensional inviscid and viscous flapping-wing flow solutions are presented. It is shown that the results are strongly dependent on flapping frequency, amplitude, and Reynolds number. These findings are substantiated by comparison with the available experimental data.

Abstract Community hospitals are an important component of the post-acute care pathway for older people. The objective of this study was to describe and contrast patients' and carers' experiences of [...]

Recent evidence suggests a role for nanobacteria in a growing number of human diseases, including renal stone formation, cardiovascular diseases, and cancer. This large body of research studies promotes the view that nanobacteria are not only alive but that they are associated with disease pathogenesis. However, it is still unclear whether they represent novel life forms, overlooked nanometer-size bacteria, or some other primitive self-replicating microorganisms. Here, we report that CaC[O.sub.3] precipitates prepared in vitro are remarkably similar to purported nanobacteria in terms of their uniformly sized, membrane-delineated vesicular shapes, with cellular division-like formations and aggregations in the form of colonies. The gradual appearance of nanobacteria-like particles in incubated human serum as well as the changes seen with their size and shape can be influenced and explained by introducing varying levels of C[O.sub.2] and NaHC[O.sub.3] as well as other conditions known to influence the precipitation of CaC[O.sub.3]. Western blotting reveals that the monoclonal antibodies, claimed to be specific for nanobacteria, react in fact with serum albumin. Furthermore, nanobacteria-like particles obtained from human blood are able to withstand high doses of [gamma]-irradiation up to 30 kGy, and no bacterial DNA is found by performing broad-range PCR amplifications. Collectively, our results provide a more plausible abiotic explanation for the unusual properties of purported nanobacteria. human serum albumin | hydroxyapatite | pathogenesis

The flapping motion of a wing based on the hind wing of the A eschnajuncea dragonfly is simulated using a three-dimensional incompressible Navier-Stokes solver. The performance of the wing is investigated by variation of a number of kinematic parameters. Flapping amplitudes of between 10 and 60 deg (half-angle) and frequencies of 1 to 300 Hz are considered, resulting in a Reynolds number range of 100 to 50,000. The flapping amplitude observed for Aeschnajuncea is shown to maximize the ratio of mean vertical force produced to power required.

The article examines local government reforms in Russia and compares the ones during President Putin's period with those before his time.

A NACA0012 airfoil undergoing pitching and plunging motion at Re = 20, 000-40,000 was simulated using a two-dimensional Navier-Stokes flow solver. Results were compared with experimental measurements in the literature and those from an inviscid analytical method and an unsteady panel method code. Although the peak in propulsive efficiency with Strouhal number demonstrated in the experimental results was predicted by the inviscid methods, it was found to be significantly modified by leading-edge vortex shedding and viscous drag at low Strouhal numbers. The occurrence and influence of vortex shedding is controlled by both the motion of the airfoil (amplitudes and phases of plunging and pitching) and the flapping frequency, which limits the time available for vortex formation and convection over the airfoil surface. Thus, Strouhal number alone is insufficient to characterize the efficiency of flapping-foil propulsion.

A theoretical approach for calculating the movement of liquid water following deposition onto a turbomachine rotor blade is described. Such a situation can occur during operation of an aero-engine in rain. The equation of motion of the deposited water is developed on an arbitrarily oriented plane triangular surface facet. By dividing the blade surface into a large number of facets and calculating the water trajectory over each one crossed in turn, the overall trajectory can be constructed. Apart from the centrifugal and Coriolis inertia effects, the forces acting on the water arise from the blade surface friction, and the aerodynamic shear and pressure gradient. Nondimensionalization of the equations of motion provides considerable insight and a detailed study of water flow on a flat rotating plate set at different stagger angles demonstrates the paramount importance of blade surface friction. The extreme cases of low and high blade friction are examined and it is concluded that the latter (which allows considerable mathematical generalization) is the most likely in practice. It is also shown that the aerodynamic shear force, but not the pressure force, may influence the water motion. Calculations of water movement on a low-speed compressor blade and the fan blade of a high bypass ratio aero-engine suggest that in low rotational speed situations most of the deposited water is centrifuged rapidly to the blade tip region. [DOI: 10.1115/1.2437780] Keywords: turbomachinery, water ingestion, water films, water deposition, water movement

The flow over a NACA0012 airfoil, oscillated sinusoidally in plunge, is simulated numerically using a two-dimensional Navier--Stokes solver at a Reynolds number of 20,000. The wake of the airfoil is visualized using a numerical particle tracing method for high reduced frequencies (1.0 < k < 10.0) and small nondimensional amplitudes (h < 0.1). Anomalous vortex shedding modes (involving multiple vortices shed per half-cycle of airfoil motion) observed experimentally in the literature are reproduced numerically and are shown to be the result of interaction between the plunging frequency and a natural bluff-body shedding frequency. This results in a vortex lock-in phenomenon analogous to that seen for oscillating cylinders. However, the lock-in boundary is not symmetric about the natural shedding frequency, due to the sharp trailing edge forcing the flow to separate at the trailing edge on the windward side of the airfoil for the majority of the plunge cycle at higher frequencies and amplitudes. DOI: 10.2514/1.23594

ABSTRACT The Eastern oyster (Crassostrea virginica) is an economically important fisheries resource along the US Gulf Coast and the eastern seaboard. In the past few years, Mississippi has ranked second [...]

The studies about the anthrax toxin which consists of three nontoxic proteins that self-assemble at the surface of receptor-bearing mammalian cells or in solution, yielding a series of toxic complexes is presented.

HE ABILITY TO READ AND WRITE for a variety of purposes is essential to success in school and in contemporary society. The purpose of this investigation was to conduct an exhaustive review of the literature and a meta-analysis of literacy research in the field of deaf education. Computer and manual searches of 40 years of peer-reviewed journal articles were conducted. A total of 964 articles related to literacy and deafness were identified and examined; 22 articles met the criteria for inclusion in the review. Results indicate that (a) no two studies examined the same dimension of literacy; (b) there was a paucity of well-designed group studies; (c) there were no systematic replication of studies; (d) there is limited data to establish evidenced-based practices. Consequently, increasing the quantity and improving the quality of research in the field is recommended.

THE NATIONAL CENTER on Low-Incidence Disabilities conducted a needs assessment of the research and training needs in the field of deaf education. A total of 331 professionals, parents, administrators, and university, faculty responded to the survey. Overall, respondents indicated that the number-one priority was to educate administrators about services that are appropriate for students who are deaf or hard of hearing. The second most important concern was how to work within the education system to change it. The third priority was teaching reading strategies. Additional priorities are reported for all respondents, as well as comparisons among the different respondent groups. Implications of the results are presented.

The three proteins that constitute anthrax toxin self-assemble into toxic complexes after one of these proteins, protective antigen (PA), binds to tumor endothelial marker 8 (TEM8) or capillary morphogenesis protein 2 (CMG2) cellular receptors. The toxin receptor complexes are internalized, and acidic endosomal pH triggers pore formation by PA and translocation of the catalytic subunits into the cytosol. In this study we show that the pH threshold for conversion of the PA prepore to the pore and for translocation differs by approximately a pH unit, depending on whether the TEM8 or CMG2 receptor is used. For TEMS-associated toxin, these events can occur at close to neutral pH values, and they show relatively low sensitivity to ammonium chloride treatment in cells. In contrast, with CMG2-associated toxin, these events require more acidic conditions and are highly sensitive to ammonium chloride. We show, furthermore, that PA dissociates from TEM8 and CMG2 upon pore formation. Our results are consistent with a model in which translocation depends on pore formation and pore formation, in turn, depends on release of PA from its receptor. We propose that because PA binds to CMG2 with much higher affinity than it does to TEM8, a lower pH is needed to attenuate CMG2 binding to allow pore formation. Our results suggest that toxin can form pores at different points in the endocytic pathway, depending on which receptor is used for entry. capillary morphogenesis protein 2 | tumor endothelial marker 8 | toxin entry

A technique is presented to efficiently solve for the currents on an appendage, e.g., antenna, attached to a planar surface of a conducting body. The appendage may be embedded in a homogeneous, dielectric material. The technique presented alleviates the complications associated with the point where the appendage is attached to the body. To illustrate the method, a wire antenna attached to an axisymmetric body is analyzed in detail. A set of coupled integral equations are formulated, appropriate quantities are expanded into Fourier modes, and coupled integral equations are derived for the Fourier coefficients of the unknowns. These equations are solved and the input admittance of the wire antenna is determined from the computed currents and is corroborated by measurements. Index Terms--Electromagnetic modeling, electromagnetic theory, equivalence principle, integral equations.

A technique is described for determining the field in a series of cascaded, axisymmetric cylindrical cavities excited by a [empty set]-independent source. The constituent cavities are axisymmetric but may have a cross-section that varies with axial displacement. A set of coupled integral equations are solved for the unknown electric fields in the apertures that separate the constituent cavities. Separate integral equations are formulated to determine the field in each cavity with a variable cross-section. Index Terms--Apertures, cavities, integral equations, transient analysis.

A technique is presented for determining the field in a series of cascaded, axisymmetric cylindrical cavities excited by a [empty set]-independent source. The constituent cavities are either coaxial or circular-cylindrical. The field in each cavity is expressed in terms of the electric field in the apertures at the interfaces where adjacent cavities join. Coupled integral equations are formulated in the frequency domain from which these aperture fields are computed. From knowledge of the aperture fields, the complete field in the cavity structure can be determined. The frequency-domain data are used to compute the time-domain field in the system of cavities. Cavities were constructed and experiments performed to corroborate the computed data. Index Terms--Apertures, cavities, integral equations, transient analysis.

Viral fusion proteins catalyze merger of viral and cell membranes through a series of steps that have not yet been well defined. To elucidate the mechanism of virus entry, we have imaged fusion between single virions bearing avian sarcoma and leukosis virus (ASLV) envelope glycoprotein (Env) and the cell membrane. Viral particles were labeled with a lipophilic dye and with palmitylated enhanced YFP that was incorporated into the inner leaflet of the viral membrane. When individual virions were bound to target cells expressing cognate receptors, they transferred their lipids and contents only when exposed to low, but not neutral, pH. These data are consistent with the proposed two-step mechanism of ASLV entry that involves receptor-priming followed by low pH activation. Most importantly, lipid mixing commonly occurred before formation of a small fusion pore that was quickly and sensitively detected by pH-dependent changes in palmitylated enhanced YFP fluorescence. Nascent fusion pores were metastable and irreversibly closed, remained small, or fully enlarged, permitting nucleocapsid delivery into the cytosol. These findings strongly imply that hemifusion and a small pore are the key intermediates of ASLV fusion. When added before low pH treatment, a peptide designed to prevent Env from folding into a final helical-bundle conformation abolished virus-cell fusion and infection. Therefore, we conclude that, after receptor-activation, Env undergoes low pH-dependent refolding into a six-helix bundle and, in doing so, sequentially catalyzes hemifusion, fusion pore opening, and enlargement. fluorescence microscopy | membrane fusion | retroviral fusion protein | single virus imaging | pore flicker

Victor Klemperer argued in 'LTI' that the Nazis used language to produce a fanatical but servile population incapable of critical thought and highly susceptible to mass suggestion. However, critics have questioned Klemperer's underlying assumptions about language, and evidence from the book itself tends to contradict his claim that the LTI or language of the Third Reich 'reigned supreme'.

Byline: John W. Young (1), Paul M. Johnson (1) Keywords: admissions models; affirmative action; college admissions; socio-economic status Abstract: In Grutter vs. Bollinger, the U.S. Supreme Court ruled that the use of race as one factor, among many in admissions decisions is constitutional. It is not known, however, whether future legal opinions will continue to uphold the use of affirmative action policies. Some have argued that class-based preferences can achieve many of the same goals as in affirmative action while being more likely to withstand legal challenges. To date, no empirical studies have been conducted on the potential impact of a class-based admissions policy if implemented at an undergraduate institution. This paper reports on a study at a selective public college and compares a number of outcomes under three admissions models: the original admissions decisions, a purely academic model, and an socio-economic status (SES)-based model. The findings showed that use of the SES-based model would have led to a more academically qualified class than in the original admitted class while maintaining substantially greater student diversity that was found under the academic model. An admissions policy based on preferences for socio-economically disadvantaged applicants appears to hold promise for other colleges and universities with similar institutional and applicant characteristics. The ideas and research design reported in this paper are based on the doctoral dissertation study of the second author, 'Undergraduate Admissions Models Incorporating Socioeconomic Factors' (Johnson, 2000). Author Affiliation: (1) Rutgers University, New Brunswick, NJ, USA Article History: Registration Date: 27/10/2004

Epithelial [Na.sup.+] channels mediate the transport of Na across epithelia in the kidney, gut, and lungs and are required for blood pressure regulation. They are inhibited by ubiquitin protein ligases, such as Nedd4 and Nedd4-2, with loss of this inhibition leading to hypertension. Here, we report that these channels are maintained in the active state by the G protein-coupled receptor kinase, Grk2, which has been previously implicated in the development of essential hypertension. We also show that Grk2 phosphorylates the C terminus of the channel [beta] subunit and renders the channels insensitive to inhibition by Nedd4-2. This mechanism has not been previously reported to regulate epithelial [Na.sup.+] channels and provides a potential explanation for the observed association of Grk2 overactivity with hypertension. Here, we report a G protein-coupled receptor kinase regulating a membrane protein other than a receptor and provide a paradigm for understanding how the interaction between membrane proteins and ubiquitin protein ligases is controlled. amiloride | ubiquitin protein ligases

The molecular events underlying the immediate steps of retroviral uncoating, occurring after membrane fusion and leading to the formation of an active reverse transcription complex, are not known. To better understand these processes, we have developed a cell-free system that recapitulates these early steps of retroviral replication by using avian sarcoma and leukosis virus as a model retrovirus. The substrates used in this system are viral particles that are trapped before completing membrane fusion. These virions are induced to fuse out of endosomes and the viral cores are released into solution where they are amenable to biochemical manipulation. This system revealed that membrane fusion is not sufficient to stimulate the formation of a reverse transcription complex. Instead, ATP hydrolysis and cellular factors >5 kDa in size are required. Furthermore, later steps of avian sarcoma and leukosis virus reverse transcription were stimulated by nuclear factors. The cell-free system should now allow for the definition of retroviral uncoating mechanisms and facilitate the identification and characterization of the cellular factors involved.

Anthrax toxin is released from Bacillus anthracis as three monomeric proteins, which assemble into toxic complexes at the surface of receptor-bearing host cells. One of the proteins, protective antigen (PA), binds to receptors and orchestrates the delivery of the other two (the lethal and edema factors) into the cytosol. PA has been shown to bind to two cellular receptors: anthrax toxin receptor/tumor endothelial marker 8 and capillary morphogenesis protein 2 (CMG2). Both are type 1 membrane proteins that include an [approximately equal to]200-aa extracellular von Willebrand factor A (VWA) domain with a metal ion-dependent adhesion site (MIDAS) motif. The anthrax toxin receptor/tumor endothelial marker 8 and CMG2 VWA domains share [approximately equal to]60% amino acid identity and bind PA directly in a metal-dependent manner. Here, we report the crystal structure of the CMG2 VWA domain, with and without its intramolecular disulfide bond, to 1.5 and 1.8 [Angstrom], respectively. Both structures contain a carboxylate ligand-mimetic bound at the MIDAS and appear as open conformations when compared with the VWA domains from [alpha]-integrins. The CMG2 structures provide a template to begin probing the high-affinity CMG2-PA interaction (200 pM) and may facilitate understanding of toxin assembly/internalization and the development of new anthrax treatments. The structural data also allow molecular interpretation of known CMG2 VWA domain mutations linked to the genetic disorders, juvenile hyaline fibromatosis, and infantile systemic hyalinosis.