Francis Bacon's doctrine of idols: a diagnosis of 'universal madness'.

The doctrine of idols is one of the most famous aspects of Bacon's thought. Yet his claim that the idols lead to madness has gone almost entirely unnoticed. This paper argues that Bacon's theory of idols underlies his diagnosis of the contemporary condition as one of 'universal madness'. In contrast to interpretations that locate his doctrine of error and recovery within the biblical narrative of the Fall, the present analysis focuses on the material and cultural sources of the mind's tendency towards error. It explains the idols in terms of Bacon's materialist psychology and his exposé of the debilitating effects of language and traditional learning. In so doing, it highlights the truly radical nature of the idols. For Bacon, the first step towards sanity was to alert people to the prevailing madness. The doctrine of idols was intended as a wake-up call, preparing the way for a remedy in the form of his new method of inquiry. The paper concludes by indicating how Bacon's method aimed to treat 'universal madness', and it suggests that his diagnosis influenced John Locke.

Elucidation of the molecular mechanisms of two nanobodies that inhibit thrombin-activatable fibrinolysis inhibitor activation and activated thrombin-activatable fibrinolysis inhibitor activity.

UNLABELLED: Essentials Thrombin-activatable fibrinolysis inhibitor (TAFI) is a risk factor for cardiovascular disorders. TAFI inhibitory nanobodies represent a promising step in developing profibrinolytic therapeutics. We have solved three crystal structures of TAFI in complex with inhibitory nanobodies. Nanobodies inhibit TAFI through distinct mechanisms and represent novel profibrinolytic leads. SUMMARY: Background Thrombin-activatable fibrinolysis inhibitor (TAFI) is converted to activated TAFI (TAFIa) by thrombin, plasmin, or the thrombin-thrombomodulin complex (T/TM). TAFIa is antifibrinolytic, and high levels of TAFIa are associated with an increased risk for cardiovascular disorders. TAFI-inhibitory nanobodies represent a promising approach for developing profibrinolytic therapeutics. Objective To elucidate the molecular mechanisms of inhibition of TAFI activation and TAFIa activity by nanobodies with the use of X-ray crystallography and biochemical characterization. Methods and results We selected two nanobodies for cocrystallization with TAFI. VHH-a204 interferes with all TAFI activation modes, whereas VHH-i83 interferes with T/TM-mediated activation and also inhibits TAFIa activity. The 3.05-Å-resolution crystal structure of TAFI-VHH-a204 reveals that the VHH-a204 epitope is localized to the catalytic moiety (CM) in close proximity to the TAFI activation site at Arg92, indicating that VHH-a204 inhibits TAFI activation by steric hindrance. The 2.85-Å-resolution crystal structure of TAFI-VHH-i83 reveals that the VHH-i83 epitope is located close to the presumptive thrombomodulin-binding site in the activation peptide (AP). The structure and supporting biochemical assays suggest that VHH-i83 inhibits TAFIa by bridging the AP to the CM following TAFI activation. In addition, the 3.00-Å-resolution crystal structure of the triple TAFI-VHH-a204-VHH-i83 complex demonstrates that the two nanobodies can simultaneously bind to TAFI. Conclusions This study provides detailed insights into the molecular mechanisms of TAFI inhibition, and reveals a novel mode of TAFIa inhibition. VHH-a204 and VHH-i83 merit further evaluation as potential profibrinolytic therapeutics.

A field test of a model for the stability of androdioecy in the freshwater shrimp, Eulimnadia texana.

The evolution of hermaphroditism from dioecy is a poorly studied transition. Androdioecy (the coexistence of males and hermaphrodites) has been suggested as an intermediate step in this evolutionary transition or could be a stable reproductive mode. Freshwater crustaceans in the genus Eulimnadia have reproduced via androdioecy for 24+ million years and thus are excellent organisms to test models of the stability of androdioecy. Two related models that allow for the stable maintenance of males and hermaphrodites rely on the counterbalancing of three life history parameters. We tested these models in the field over three field seasons and compared the results to previous laboratory estimates of these three parameters. Male and hermaphroditic ratios within years were not well predicted using either the simpler original model or a version of this model updated to account for differences between hermaphroditic types ('monogenic' and 'amphigenic' hermaphrodites). Using parameter estimates of the previous year to predict the next year's sex ratios revealed a much better fit to the original relative to the updated version of the model. Therefore, counter to expectations, accounting for differences between the two hermaphroditic types did not improve the fit of these models. At the moment, we lack strong evidence that the long-term maintenance of androdioecy in these crustaceans is the result of a balancing of life history parameters; other factors, such as metapopulation dynamics or evolutionary constraints, may better explain the 24+ million year maintenance of androdioecy in clam shrimp.

The effects of river run-off on water clarity across the central Great Barrier Reef.

Changes in water clarity across the shallow continental shelf of the central Great Barrier Reef were investigated from ten years of daily river load, oceanographic and MODIS-Aqua data. Mean photic depth (i.e., the depth of 10% of surface irradiance) was related to river loads after statistical removal of wave and tidal effects. Across the ∼25,000 km(2) area, photic depth was strongly related to river freshwater and phosphorus loads (R(2)=0.65 and 0.51, respectively). In the six wetter years, photic depth was reduced by 19.8% and below water quality guidelines for 156 days, compared to 9 days in the drier years. After onset of the seasonal river floods, photic depth was reduced for on average 6-8 months, gradually returning to clearer baseline values. Relationships were strongest inshore and midshelf (∼12-80 km from the coast), and weaker near the chronically turbid coast. The data show that reductions in river loads would measurably improve shelf water clarity, with significant ecosystem health benefits.

Medical student appraisal: electronic resources for inpatient pre-rounding.

BACKGROUND: Pre-rounding is essential to preparing for morning rounds. Despite its importance, pre-rounding is rarely formally taught within the medical school curriculum and more often informally learned by modeling residents. The evolution of mobile applications provides opportunities to optimize this process. OBJECTIVES: To evaluate three options available to medical students while pre-rounding and promote adoption of mobile resources in clinical care. METHODS: Six medical students formed the evaluation cohort. Students were surveyed to assess pre-rounding practices. Participants utilized paper-based pre-rounding templates for two weeks followed by two weeks of the electronic note-taking service Evernote. A review of mobile applications on the iTunes and Google Play stores was performed, with each application informally reviewed by a single student. The application Scutsheet was selected for formal review by all students. Data was collected from narrative responses supplied by students throughout the evaluation periods and aggregated to assess strengths and limitations of each application. RESULTS: Pre-study responses demonstrated two consistent processes: verbal sign-out of overnight events and template use to organize patient information. The paper-based template was praised for its organization and familiarity amongst residents, but perceived as limited by the requirement of re-copying data into the hospital's electronic medical record (EMR). Evernote excelled due to compatibility across multiple operating systems, including accessibility from clinical workstations and ability to copy notes into the hospital's EMR. Scutsheet allowed for retention of data across multiple hospital days, but was limited by inability to export data or modify the electronic template. Aggregated user feedback identified the abilities to customize templates and copy information into the EMR as two prevailing characteristics that enhanced the efficiency of pre-rounding. DISCUSSION: Mobile devices offer the potential to enhance pre-rounding efficiency for medical students and residents. A customizable Evernote-based system is described in sufficient detail for reproduction by interested students.

Unusually high levels of n-6 polyunsaturated fatty acids in whale sharks and reef manta rays.

Fatty acid (FA) signature analysis has been increasingly used to assess dietary preferences and trophodynamics in marine animals. We investigated FA signatures of connective tissue of the whale shark Rhincodon typus and muscle tissue of the reef manta ray Manta alfredi. We found high levels of n-6 polyunsaturated fatty acids (PUFA), dominated by arachidonic acid (20:4n-6; 12-17 % of total FA), and comparatively lower levels of the essential n-3 PUFA-eicosapentaenoic acid (20:5n-3; ~1 %) and docosahexaenoic acid (22:6n-3; 3-10 %). Whale sharks and reef manta rays are regularly observed feeding on surface aggregations of coastal crustacean zooplankton during the day, which generally have FA profiles dominated by n-3 PUFA. The high levels of n-6 PUFA in both giant elasmobranchs raise new questions about the origin of their main food source.

Medical student appraisal: applications for bedside patient education.

BACKGROUND: Medical students are often afforded the privilege of counselling patients. In the past resources were limited to pen and paper or anatomic models. The evolution of mobile applications allows for limitless access to resources that facilitate bedside patient education. OBJECTIVES: To evaluate the utility of six applications in patient education and promote awareness of implementing mobile resources in clinical care. METHODS: Six medical students rotating on various clerkships evaluated a total of six mobile applications. Strengths, limitations, and suggested uses in clinical care were identified. Applications included Meditoons™, VisiblePatient™, DrawMD™, CardioTeach™, Visual Anatomy™, and 360° Patient Education Suite™. Data was generated from narrative responses supplied by each student during their evaluation period. RESULTS: Bedside teaching was enhanced by professional illustrations and animations depicting anatomy and pathophysiology. Impromptu teaching was facilitated, as resources were conveniently available on a student's smartphone or tablet. The ability to annotate and modify images and subsequently email to patients was an extraordinary improvement in provider-patient communication. Universal limitations included small smartphone screens and the novelty of new technology. DISCUSSION: Mobile applications have the potential to greatly enhance patient education and simultaneously build rapport. Endless opportunities exist for their integration in clinical practice, particularly for new diagnoses, consent for procedures, and at time of discharge. Providers should be encouraged to try new applications and utilize them with patients.

Medical student appraisal: searching on smartphones.

BACKGROUND: The rapidly growing industry for mobile medical applications provides numerous smartphone resources designed for healthcare professionals. However, not all applications are equally useful in addressing the questions of early medical trainees. METHODS: Three popular, free, mobile healthcare applications were evaluated along with a Google(TM) web search on both Apple(TM) and Android(TM) devices. Six medical students at a large academic hospital evaluated each application for a one-week period while on various clinical rotations. RESULTS: Google(TM) was the most frequently used search method and presented multimedia resources but was inefficient for obtaining clinical management information. Epocrates(TM) Pill ID feature was praised for its clinical utility. Medscape(TM) had the highest satisfaction of search and excelled through interactive educational features. Micromedex(TM) offered both FDA and off-label dosing for drugs. DISCUSSION: Google(TM) was the preferred search method for questions related to basic disease processes and multimedia resources, but was inadequate for clinical management. Caution should also be exercised when using Google(TM) in front of patients. Medscape(TM) was the most appealing application due to a broad scope of content and educational features relevant to medical trainees. Students should also be cognizant of how mobile technology may be perceived by their evaluators to avoid false impressions.

Structural basis of bacterial defense against g-type lysozyme-based innate immunity.

Gram-negative bacteria can produce specific proteinaceous inhibitors to defend themselves against the lytic action of host lysozymes. So far, four different lysozyme inhibitor families have been identified. Here, we report the crystal structure of the Escherichia coli periplasmic lysozyme inhibitor of g-type lysozyme (PliG-Ec) in complex with Atlantic salmon g-type lysozyme (SalG) at a resolution of 0.95 Å, which is exceptionally high for a complex of two proteins. The structure reveals for the first time the mechanism of g-type lysozyme inhibition by the PliG family. The latter contains two specific conserved regions that are essential for its inhibitory activity. The inhibitory complex formation is based on a double 'key-lock' mechanism. The first key-lock element is formed by the insertion of two conserved PliG regions into the active site of the lysozyme. The second element is defined by a distinct pocket of PliG accommodating a lysozyme loop. Computational analysis indicates that this pocket represents a suitable site for small molecule binding, which opens an avenue for the development of novel antibacterial agents that suppress the inhibitory activity of PliG.

Biology, ecology and conservation of the Mobulidae.

The Mobulidae are zooplanktivorous elasmobranchs comprising two recognized species of manta rays (Manta spp.) and nine recognized species of devil rays (Mobula spp.). They are found circumglobally in tropical, subtropical and temperate coastal waters. Although mobulids have been recorded for over 400 years, critical knowledge gaps still compromise the ability to assess the status of these species. On the basis of a review of 263 publications, a comparative synthesis of the biology and ecology of mobulids was conducted to examine their evolution, taxonomy, distribution, population trends, movements and aggregation, reproduction, growth and longevity, feeding, natural mortality and direct and indirect anthropogenic threats. There has been a marked increase in the number of published studies on mobulids since c. 1990, particularly for the genus Manta, although the genus Mobula remains poorly understood. Mobulid species have many common biological characteristics although their ecologies appear to be species-specific, and sometimes region-specific. Movement studies suggest that mobulids are highly mobile and have the potential to rapidly travel large distances. Fishing pressure is the major threat to many mobulid populations, with current levels of exploitation in target fisheries unlikely to be sustainable. Advances in the fields of population genetics, acoustic and satellite tracking, and stable-isotope and fatty-acid analyses will provide new insights into the biology and ecology of these species. Future research should focus on the uncertain taxonomy of mobulid species, the degree of overlap between their large-scale movement and human activities such as fisheries and pollution, and the need for management of inter-jurisdictional fisheries in developing nations to ensure their long-term sustainability. Closer collaboration among researchers worldwide is necessary to ensure standardized sampling and modelling methodologies to underpin global population estimates and status.

Three-dimensional structure of α-crystallin domain dimers of human small heat shock proteins HSPB1 and HSPB6.

Small heat shock proteins (sHSPs) are a family of evolutionary conserved ATP-independent chaperones. These proteins share a common architecture defined by a signature α-crystallin domain (ACD) flanked by highly variable N- and C-terminal extensions. The ACD, which has an immunoglobulin-like fold, plays an important role in sHSP assembly. This domain mediates dimer formation of individual protomers, which then may assemble into larger oligomers. In vertebrate sHSPs, the dimer interface is formed by the symmetrical antiparallel pairing of two ß-strands (ß7), generating an extended ß-sheet on one face of the ACD dimer. Recent structural studies of isolated ACDs from a number of vertebrate sHSPs suggest a variability in the register of the ß7/ß7 strand interface, which may, in part, give rise to the polydispersity often associated with the full-length proteins. To further analyze the structure of ACD dimers, we have employed a combination of X-ray crystallography and solution small-angle X-ray scattering (SAXS) to study the ACD-containing fragments of human HSPB1 (HSP27) and HSPB6 (HSP20). Unexpectedly, the obtained crystal structure of the HSPB1 fragment does not reveal the typical ß7/ß7 dimers but, rather, hexamers formed by an asymmetric contact between the ß4 and the ß7 strands from adjacent ACDs. Nevertheless, in solution, both ACDs form stable dimers via the symmetric antiparallel interaction of ß7 strands. Using SAXS, we show that it is possible to discriminate between different putative registers of the ß7/ß7 interface, with the results indicating that, under physiological conditions, there is only a single register of the strands for both proteins.

How large is the world's largest fish? Measuring whale sharks Rhincodon typus with laser photogrammetry.

Laser photogrammetry was found to be a promising new cost-effective technique for measuring free-swimming whale sharks Rhincodon typus. Photogrammetric measurements were more precise than visual size estimates by experienced researchers, with results from the two methods differing by 9· 8 ± 1· 1% (mean ±s.e.). A new metric of total length and the length between the fifth gill and first dorsal fin (r² = 0· 93) is proposed to facilitate easy, accurate length measurements of whale sharks in the field.

Sex chromosome evolution in the clam shrimp, Eulimnadia texana.

Chromosomes that determine sex are predicted to evolve differently than autosomes: a lack of recombination on one of the two sex chromosomes is predicted to allow an accumulation of deleterious alleles that eventually leads to reduced functionality and potential physical degradation of the nonrecombining chromosome. Because these changes should occur at an elevated evolutionary rate, it is difficult to find appropriate species in which to test these evolutionary predictions. The unique genetic sex-determining mechanism of the crustacean Eulimnadia texana prevents major chromosome degeneration because of expression of both 'proto-sex' (i.e. early stage of development) chromosomes in homozygous form (ZZ and WW). Herein, we exploit this unique genetic system to examine the predicted accumulation of deleterious alleles by comparing both homogametic sexual types to their heterogametic counterpart. We report differences in crossing over in a sex-linked region in the ZW hermaphrodites (approximately 3%) relative to the ZZ males (approximately 21%), indicative of cross-over suppression in the ZW hermaphrodites. Additionally, we report that both ZZ and WW genotypes have reduced fitness relative to ZW hermaphrodites, which is consistent with the prediction of harboured recessive mutations embedded on both the Z and the W chromosomes. These results suggest that the proto-sex chromosomes in E. texana accumulate recessive deleterious alleles. We hypothesize that recessive deleterious alleles of large effect cannot accumulate because of expression in both ZZ and WW individuals, keeping both chromosomes from losing significant function.

Evolutionary transitions among dioecy, androdioecy and hermaphroditism in limnadiid clam shrimp (Branchiopoda: Spinicaudata).

Examinations of breeding system transitions have primarily concentrated on the transition from hermaphroditism to dioecy, likely because of the preponderance of this transition within flowering plants. Fewer studies have considered the reverse transition: dioecy to hermaphroditism. A fruitful approach to studying this latter transition can be sought by studying clades in which transitions between dioecy and hermaphroditism have occurred multiple times. Freshwater crustaceans in the family Limnadiidae comprise dioecious, hermaphroditic and androdioecious (males + hermaphrodites) species, and thus this family represents an excellent model system for the assessment of the evolutionary transitions between these related breeding systems. Herein we report a phylogenetic assessment of breeding system transitions within the family using a total evidence comparative approach. We find that dioecy is the ancestral breeding system for the Limnadiidae and that a minimum of two independent transitions from dioecy to hermaphroditism occurred within this family, leading to (1) a Holarctic, all-hermaphrodite species, Limnadia lenticularis and (2) mixtures of hermaphrodites and males in the genus Eulimnadia. Both hermaphroditic derivatives are essentially females with only a small amount of energy allocated to male function. Within Eulimnadia, we find several all-hermaphrodite populations/species that have been independently derived at least twice from androdioecious progenitors within this genus. We discuss two adaptive (based on the notion of 'reproductive assurance') and one nonadaptive explanations for the derivation of all-hermaphroditism from androdioecy. We propose that L. lenticularis likely represents an all-hermaphrodite species that was derived from an androdioecious ancestor, much like the all-hermaphrodite populations derived from androdioecy currently observed within the Eulimnadia. Finally, we note that the proposed hypotheses for the dioecy to hermaphroditism transition are unable to explain the derivation of a fully functional, outcrossing hermaphroditic species from a dioecious progenitor.

Development of in vitro correlate assays of immunity to infection with Yersinia pestis.

Pneumonic plague is a severe, rapidly progressing disease for which there is no effective vaccine. Since the efficacy of new vaccines cannot be tested in humans, it is essential to develop in vitro surrogate assays that are valid predictors of immunity. The F1 capsule antigen stimulates a protective immune response to most strains of Yersinia pestis. However, strains of Y. pestis that are F1- but still virulent have been isolated, and an in vitro assay, the results which can predict protection against both F1+ and F1- strains, is needed. The virulence antigen (V) is an essential virulence factor of Y. pestis and stimulates protective antibodies. We investigated potential correlates of plague immunity that are based on anti-V antibody-mediated neutralization of Yersinia-induced macrophage cytotoxicity. The neutralizing activity of sera from mice vaccinated with an F1-V fusion candidate vaccine was determined. The decrease in the level of the apoptosis-specific enzyme caspase-3 significantly predicted survival in one- and two-dose vaccination experiments. Sera from F1-V-vaccinated nonhuman primates were evaluated with macrophage assays based on caspase-3 and on other markers manifested at the different stages in cell death. Using murine- and human-derived macrophages in microscopic and fluorescence-activated-cell-sorting-based live/dead staining assays of terminal necrosis, we demonstrated a strong association between in vitro neutralization of macrophage cytotoxicity induced by serum-treated Yersinia and in vivo protection against lethal infection. These results provide a strong base for the development of reliable in vitro correlate bioassays that are predictive of protective immunity to plague.

Outcomes of myringoplasty in Australian Aboriginal children and factors associated with success: a prospective case series.

The objective of this study was to assess the outcomes of myringoplasties in Aboriginal children and to identify factors associated with a successful outcome with the use of prospective case series from primary health care clinics and hospitals in four rural and remote regions of Western Australia. All 58 Aboriginal children, aged 5-15 years, who underwent 78 myringoplasties between 1 January 2000 and 30 June 2001 were included in the study. Complete postoperative (post-op) follow-up was achieved following 78% of myringoplasties. The main outcome measures were (a) success, i.e. an intact tympanic membrane and normal hearing six or more months post-op in the operated ear, (b) closure of the perforation, (c) Post-op hearing improvement. Forty-nine per cent of myringoplasties were successful, 72% resulted in closure or reduction in the size of the perforation and 51% resulted in hearing improvement. After controlling for age, sex, clustering and number of previous myringoplasties, no association was observed between success or hearing improvement and perforation size, or the presence of serous aural discharge at the time of surgery. Myringoplasty resulted in hearing improvement and/or perforation closure in a significant proportion of children. Thus, primary school-aged Aboriginal children in whom conservative management of chronic suppurative otitis media has been unsuccessful should have access to myringoplasty because of the positive impact on their socialization, language and learning that results from improved hearing.

Levels of inbreeding depression over seven generations of selfing in the androdioecious clam shrimp, Eulimnadia texana.

Androdioecy (mixtures of males and hermaphrodites) is a rare mating system in both plants and animals. Theory suggests that high levels of inbreeding depression can maintain males in androdioecious populations if hermaphrodites commonly self-fertilize. However, if inbreeding depression (delta) can be 'purged' from selfing populations, maintaining males is more difficult. In the androdioecious clam shrimp, Eulimnadia texana, delta is estimated to be as high as 0.7. Previous work suggests that this high level is maintained in the face of high levels of inbreeding due to an associative overdominance of fitness-related loci with the sex-determining locus. Such associative overdominance would make purging of inbreeding depression difficult to impossible. The current experiment was designed to determine if delta can be purged in these shrimp by tracking fitness across seven generations in selfing and outcrossing treatments. Evidence of purging was found in one of four populations, but the remaining populations demonstrated a consistent pattern of delta across generations. Although the experimental design allowed ample opportunity for purging, the majority of populations were unable to purge their genetic load. Therefore, delta in this species is likely due to associative overdominance caused by deleterious recessive alleles linked to the sex determining locus.

In-vitro characterisation of the phagocytosis and fate of anthrax spores in macrophages and the effects of anti-PA antibody.

Antibodies (Abs) to the protective antigen (PA) component of the anthrax toxins have anti-spore as well as anti-toxin activities. Anti-PA antisera and purified anti-PA Abs enhance the phagocytosis by murine-derived macrophages (MQs) of spores of the Ames and Sterne strains and retard the germination of extracellular spores in vitro. The fate after phagocytosis of untreated and anti-PA-treated spores was further studied in culture medium that supported phagocytosis without stimulating spore germination (Dulbecco's minimal essential medium with horse serum 10%). The spores germinated within cells of primary peritoneal murine MQs (C3H/HeN) and MQs of the RAW264.7 MQ-like cell line; germination was associated with a rapid decline in spore viability. Exposure of MQs to inhibitors of phago-endosomal acidification (bafilomycin A and chloroquine) reduced the efficiency of MQ killing and allowed outgrowth and replication of the organisms. Treatment of spores with anti-PA Abs stimulated their phagocytosis and was associated with enhanced MQ killing of the spores. The enhanced killing of spores correlated with the greater extent of germination of anti-PA-treated spores after phagocytosis. A PA null mutant of the Ames strain exhibited none of the effects associated with anti-PA Ab treatment ofthe parental strain. Thus, the anti-PA Ab-specific immunity induced by vaccines has anti-spore activities and its role in impeding the early stages of infection with Bacillusanthracis needs to be assessed.

Anti-V antigen antibody protects macrophages from Yersinia pestis -induced cell death and promotes phagocytosis.

The pathogenic Yersinia spp. harbor a common plasmid (pYV) essential for virulence. The plasmid encodes a type III secretion system that functions to translocate Yersinia outer proteins (Yops) into the host cytosol. Within the host cell, the Yops act to inhibit phagocytosis and induce apoptosis. One of the plasmid-encoded proteins, virulence antigen (V), is a major protective immunogen that is involved in Yop translocation. Yersinia pestis, like the enteric Yersinia spp., was both resistant to phagocytosis by and cytotoxic for J774.A1, a murine macrophage cell line. Both of these activities were dependent on culture of the bacteria at 37 degrees C for 1.5-2 h before infection. However, extending the preculture period at 37 degrees C to 24 h, which induced formation of a capsule, completely blocked cytotoxicity. Treating the bacteria with either rabbit polyclonal anti-V antibodies (R anti-V) or monoclonal antibody (MAb) 7.3, antibodies specific for V and protective against plague in vivo, protected J774.A1 cells from Y. pestis -induced cell death and also reversed the inhibition of phagocytosis. Whereas protection against cell cytotoxicity was afforded by the F(ab')(2) portion of R anti-V, the ability of anti-V to induce uptake of Y. pestis appeared to be dependent on the Fc portion of the Ab. The protective epitope(s) recognized by R anti-V was contained in the central region of Y. pestis V (aa 135-275) and were partially cross reactive with Y. pseudotuberculosis and Y. enterocolitica serotype 08 V antigens.