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Using insights from her field of West African art and ethnography, Laura Smalligan (in an earlier journal article concerning the Jamaican slave dance, Jonkonnu) opens up and renews challenging perspectives regarding the indispensable African content of New World slavery. Smalligan argues that the Connu slave pageant stemmed from a particular time, place and outlook (of slaves from the Bight of Biafra, modern Nigeria). Discussion here pivots on two comparisons: of dance, often accompanied by trance states (from West Africa to Anglophone plantation societies in the Caribbean and mainland North America); and, of the way contemporary scholars now – often smitten in this generation by the postmodern ‘literary turn’ – view, prematurely, slave ethnicity as heuristically vague and unmanageable, as opposed to local slave society people, black and white, then who in their ordinary talk and activities depicted certain slaves ethnically (and linguistically). These broad comparisons should deepen and advance understan...

Affinity purification coupled to mass spectrometry (AP-MS) represents a powerful and proven approach for the analysis of protein-protein interactions. However, the detection of true interactions for proteins that are commonly considered background contaminants is currently a limitation of AP-MS. Here using spectral counts and the new statistical tool, Significance Analysis of INTeractome (SAINT), true interaction between the serine/threonine protein phosphatase 5 (PP5) and a chaperonin, heat shock protein 90 (Hsp90), is discerned. Furthermore, we report and validate a new interaction between PP5 and an Hsp90 adaptor protein, stress-induced phosphoprotein 1 (STIP1; HOP). Mutation of PP5, replacing key basic amino acids (K97A and R101A) in the tetratricopeptide repeat (TPR) region known to be necessary for the interactions with Hsp90, abolished both the known interaction of PP5 with cell division cycle 37 homolog and the novel interaction of PP5 with stress-induced phosphoprotein 1. Taken together, the results presented demonstrate the usefulness of label-free quantitative proteomics and statistical tools to discriminate between noise and true interactions, even for proteins normally considered as background contaminants.

Summary Background The assembly of a robust microtubule-based mitotic spindle is a prerequisite for the accurate segregation of chromosomes to progeny. Spindle assembly relies on the concerted action of centrosomes, spindle microtubules, molecular motors, and nonmotor spindle proteins. Results Here we use an RNA-interference screen of the human centrosome proteome to identify novel regulators of spindle assembly. One such regulator is HAUS, an 8-subunit protein complex that shares homology to Drosophila Augmin. HAUS localizes to interphase centrosomes and to mitotic spindle microtubules, and its disruption induces microtubule-dependent fragmentation of centrosomes along with an increase in centrosome size. HAUS disruption results in the destabilization of kinetochore microtubules and the eventual formation of multipolar spindles. These severe mitotic defects are alleviated by codepletion of NuMA, indicating that both factors regulate opposing activities. HAUS disruption alters NuMA localization, suggesting that mislocalized NuMA activity contributes to the spindle and centrosome defects observed. Conclusion The human Augmin complex (HAUS) is a critical and evolutionary conserved multisubunit protein complex that regulates centrosome and spindle integrity.

The serine/threonine protein phosphatases are targeted to specific subcellular locations and substrates in part via interactions with a wide variety of regulatory proteins. Understanding these interactions is thus critical to understanding phosphatase function. Using an iterative affinity purification/mass spectrometry approach, we generated a high density interaction map surrounding the protein phosphatase 2A catalytic subunit. This approach recapitulated the assembly of the PP2A catalytic subunit into many different trimeric complexes but also revealed several new protein-protein interactions. Here we define a novel large multiprotein assembly, referred to as the striatin-interacting phosphatase and kinase (STRIPAK) complex. STRIPAK contains the PP2A catalytic (PP2Ac) and scaffolding (PP2A A) subunits, the striatins (PP2A regulatory B''' subunits), the striatin-associated protein Mob3, the novel proteins STRIP1 and STRIP2 (formerly FAM40A and FAM40B), the cerebral cavernous malformation 3 (CCM3) protein, and members of the germinal center kinase III family of Ste20 kinases. Although the function of the CCM3 protein is unknown, the CCM3 gene is mutated in familial cerebral cavernous malformations, a condition associated with seizures and strokes. Our proteomics survey indicates that a large portion of the CCM3 protein resides within the STRIPAK complex, opening the way for further studies of CCM3 biology. The STRIPAK assembly establishes mutually exclusive interactions with either the CTTNBP2 proteins (which interact with the cytoskeletal protein cortactin) or a second subcomplex consisting of the sarcolemmal membrane-associated protein (SLMAP) and the related coiled-coil proteins suppressor of IKKepsilon (SIKE) and FGFR1OP2. We have thus identified several novel PP2A-containing protein complexes, including a large assembly linking kinases and phosphatases to a gene mutated in human disease.

First case of infective endocarditis on a percutaneous aortic valve replacement due to Moraxalla nonliquefaciens in 64 year old woman. It was successfully treated medically with antibiotics. She had not suitable for surgical aortic valve replacement due to 3 sternotomies for thymoma resection and subsequent radiotherapy with blocked major thoracic veins. Due to her azathioprine immunosuppresion (myasthenia) she may have been at increased endocarditis risk. We suggest prophylactic antibiotics at implant for this group in future.

The RhoGEF GEF-H1 can be sequestered in an inactive state on polymerized microtubules by the dynein motor light-chain Tctex-1. Phosphorylation of GEF-H1 Ser885 by PKA or PAK kinases creates an inhibitory 14-3-3-binding site. Here we show a new mode of GEF-H1 activation in response to the G-protein-coupled receptor (GPCR) ligands lysophosphatidic acid (LPA) or thrombin that is independent of microtubule depolymerization. LPA/thrombin stimulates disassembly of the GEF-H1:dynein multi-protein complex through the concerted action of Gα and Gβγ. Gα binds directly to GEF-H1 and displaces it from Tctex-1, while Gβγ binds to Tctex-1 and disrupts its interaction with the dynein intermediate chain, resulting in the release of GEF-H1. Full activation of GEF-H1 requires dephosphorylation of Ser885 by PP2A, which is induced by thrombin. The coordinated displacement of GEF-H1 from microtubules by G-proteins and its dephosphorylation by PP2A demonstrate a multistep GEF-H1 activation and present a unique mechanism coupling GPCR signalling to Rho activation.

CEP192 is a centrosome protein that plays a critical role in centrosome biogenesis and function in mammals, Drosophila and C. elegans.1-6 Moreover, CEP192-depleted cells arrest in mitosis with disorganized microtubules, suggesting that CEP192’s function in spindle assembly goes beyond its role in centrosome activity and pointing to a potentially more direct role in the regulation of the mitotic microtubule landscape.7 To better understand CEP192 function in mitosis, we used mass spectrometry to identify CEP192-interacting proteins. We previously reported that CEP192 interacts with NEDD1, a protein that associates with the γ-tubulin ring complex (γ-TuRC) and regulates its phosphorylation status during mitosis.8 Additionally, within the array of proteins that interact with CEP192, we identified the microtubule binding K63-deubiquitinase CYLD. Further analyses show that co-depletion of CYLD alleviates the bipolar spindle assembly defects observed in CEP192-depleted cells. This functional relationship exposes an intriguing role for CYLD in spindle formation and raises the tantalizing possibility that CEP192 promotes robust mitotic spindle assembly by regulating K63-polyubiquitin-mediated signaling through CYLD.

The binding of the eukaryotic initiation factor 4E (eIF4E) to the mRNA 5′ cap structure is a rate-limiting step in mRNA translation initiation. eIF4E promotes ribosome recruitment to the mRNA. In Drosophila, the eIF4E homologous protein (d4EHP) forms a complex with binding partners to suppress the translation of distinct mRNAs by competing with eIF4E for binding the 5′ cap structure. This repression mechanism is essential for the asymmetric distribution of proteins and normal embryonic development in Drosophila. In contrast, the physiological role of the mammalian 4EHP (m4EHP) was not known. In this study, we have identified the Grb10-interacting GYF protein 2 (GIGYF2) and the zinc finger protein 598 (ZNF598) as components of the m4EHP complex. GIGYF2 directly interacts with m4EHP, and this interaction is required for stabilization of both proteins. Disruption of the m4EHP-GIGYF2 complex leads to increased translation and perinatal lethality in mice. We propose a model by which the m4EHP-GIGYF2 complex represses translation of a subset of mRNAs during embryonic development, as was previously reported for d4EHP.

Identifying the interactions established by a protein of interest can be a critical step in understanding its function. This is especially true when an unknown protein of interest is demonstrated to physically interact with proteins of known function. While many techniques have been developed to characterize protein-protein interactions, one strategy that has gained considerable momentum over the past decade for identification and quantification of protein-protein interactions, is affinity-purification followed by mass spectrometry (AP-MS). Here, we briefly review the basic principles used in affinity-purification coupled to mass spectrometry, with an emphasis on tools (both biochemical and computational), which enable the discovery and reporting of high quality protein-protein interactions.

Genome integrity is jeopardized each time DNA replication forks stall or collapse. Here we report the identification of a complex composed of MMS22L (C6ORF167) and TONSL (NFKBIL2) that participates in the recovery from replication stress. MMS22L and TONSL are homologous to yeast Mms22 and plant Tonsoku/Brushy1, respectively. MMS22L-TONSL accumulates at regions of ssDNA associated with distressed replication forks or at processed DNA breaks, and its depletion results in high levels of endogenous DNA double-strand breaks caused by an inability to complete DNA synthesis after replication fork collapse. Moreover, cells depleted of MMS22L are highly sensitive to camptothecin, a topoisornerase I poison that impairs DNA replication progression. Finally, MMS22L and TONSL are necessary for the efficient formation of RAD51 foci after DNA damage, and their depletion impairs homologous recombination. These results indicate that MMS22L and TONSL are genome caretakers that stimulate the recombination-dependent repair of stalled or collapsed replication forks.

Total anomalous venous drainage is a rare congenital cardiac defect seen in 1% of the population; there is usually a concomitant atrial septal defect. We discuss such a diagnostic challenge in a patient who presented on a number of occasions with acute respiratory distress and haemoptysis. True understanding of her underlying congenital heart disease was not appreciated until review in a congenital heart disease clinic - in which she presented for prepregnancy counselling. She was found to have a stricture at the site of anastomosis of the common chamber with the left atrium, resulting in pulmonary venous hypertension leading to acute presentation of pulmonary haemorrhages. She underwent successful full balloon dilatation of the site, leading to full recovery. Most patients are diagnosed at birth and undergo surgical repair. The outcome is good, and historically it has been regarded that it is unusual for them to have long-term complications, although dysrhythmias remain a recognized long-term complication. Surgery for total anomalous pulmonary venous drainage is nevertheless a palliation, and it is vital that the possible role of late complications is considered in all cases.

Neutrophil chemotaxis depends on actin dynamics, but the roles for specific cytoskeleton regulators in this response remain unclear. By analysis of mammalian diaphanous-related formin 1 (mDia1)-deficient mice, we have identified an essential role for this actin nucleator in neutrophil chemotaxis. Lack of mDia1 was associated with defects in chemoattractant-induced neutrophil actin polymerization, polarization, and directional migration, and also with impaired activation of RhoA, its downstream target p160-Rho-associated coil-containing protein kinase (ROCK), and the leukemia-associated RhoA guanine nucleotide exchange factor (LARG). Our data also revealed mDia1 to be associated with another cytoskeletal regulator, Wiskott-Aldrich syndrome protein (WASp), at the leading edge of chemotaxing neutrophils and revealed polarized morphology and chemotaxis to be more mildly impaired in WAS−/− than in mDia1−/− neutrophils, but essentially abrogated by combined mDia1/WASp deficiency. Thus, mDia1 roles in neutrophil chemotaxis appear to be subserved in concert with WASp and are realized at least in part by activation of the LARG/RhoA/ROCK signaling pathway.

Studies have suggested that occupational disease and injury are under-recognized by clinicians. To estimate the frequency of occupational factors in disease and injury, 108 patients in a general (not occupational) health care facility were interviewed about the frequency and types of workplace-health interactions. Thirty-nine percent reported possible causation by work, and 66% reported a possible increase in symptoms by work, even if not caused by work. Twenty-seven percent reported changing jobs and/or tasks because of work-health interactions. The majority of men and women reported that worksite changes could improve their functional ability at work. This study therefore indicates that (1) occupational health concerns are common in primary care clinics, even if not addressed by clinicians; (2) the definition of occupational health concerns should be broadened to include disease caused by work, disease symptoms worsened by work, and the need for occupational accommodation even if the disease itself is not caused by work; and (3) inquiring about patient concerns about workplace-health interactions can provide clinicians with significant opportunities for primary, secondary, and tertiary prevention.

That the performance of Shakespeare's plays entails special and complex interpretation is readily acknowledged by theater historians, literary critics, and theater artists. Their attention, however, focuses on the directors and the actors. Set and costume design usually get short shrift unless they embody a special concept or idiosyncratic interpretation of the play: the staging of Antony and Cleopatra updated to British Egypt, a modern-dress Hamlet or, say, an expressionistic Macbeth. Otherwise, the work of the designer is often thought to be merely decorative or illustrative, providing a space for the action, with scenery and costumes appropriate to the play's historical period. In this light, the designer's task seems to be rather straightforward to adapt fashions by modern tailoring and to create scenery that suggests the play's period and place.

B ORN IN THE BICENTENNIAL FERVOR OF 1976, it was to be a grand AngloAmerican enterprise, the cultural equivalent of the Normandy landing, the Lend-Lease Act, and the Marshall Plan all rolled into one. The British Broadcasting Corporation and Time-Life Television would produce all the plays in special made-for-television productions tailored to general audiences. Designed to be enduring and easily understood, the productions would deliberately adhere to a plain style: "William Shakespeare wrote his plays to please an audience that was neither very sophisticated nor literary," said Shaun Sutton, head of the BBC's television drama group, and "we hope to bring back these plays on the same plain terms to a mass audience that would have astounded Shakespeare. Undoubtedly, the project will have a wide educational future; but primarily, the plays will be presented as they were first conceived-as entertainment."I Underwriters for the $13.6 million venture were to be three corporate giants: Exxon Corporation, Morgan Guaranty Trust Company of New York, and Metropolitan Life Insurance Company. The Corporation for Public Broadcasting (CPB) would supply funding for ancillary educational activities, including special programs on National Public Radio. And WNET/Thirteen in New York would coordinate the broadcasts and educational outreach in the United States. Pointing out that American funding came to only $100,000 a play, WNET President John Jay Iselin accurately summed up the high hopes with which the series began, calling it "the great Anglo-American alliance of the twentieth century." Iselin predicted that it would bring about "a Shakespeare Renaissance and a special educational experience for a generation of Americans. "2 Such were the high spirits that inspired the unusual collaboration of television

(1985). Women, and the comparative study of American Negro slavery. Slavery & Abolition: Vol. 6, No. 1, pp. 25-40.

Sir Herbert Beerbohm Tree (1853–1917) is a perplexing figure in Shakespearean stage history. At the turn of the century and in the decade following, he was esteemed as Irving's successor, the pre-eminent Shakespearean actor and producer in Great Britain. That reputation rested largely on his great “revivals” of Shakespeare at Her (later His) Majesty's Theatre. Highly regarded in his own day, Tree is now commonly thought of as a somewhat ludicrous impressario: “He was at heart a comedian, a character actor, a make-up artist specializing in the eccentric,” writes Charles H. Shattuck in his authoritative history of Shakespeare in performance. And, Shattuck continues, Tree's staging is remembered chiefly for its “tricky business, tableaux and dumbshows,” the kind of elaborate, literal-minded stage “illustration” which put a barge onstage in Antony and Cleopatra and live rabbits in A Midsummer Night's Dream. It is easy to laugh at Tree's excesses, as many have, because so little is known about his achievements. For until 1974 the Tree promptbooks and theatre records (scrapbooks with complete newspaper reviews) were controlled by the Tree Estate, and were therefore all but inaccessible to scholars. Lacking the direct evidence of reviews and promptbooks, theatre historians have relied on the harsh judgments of Tree's enemies—chiefly George Bernard Shaw and A. B. Walkley of the London Times—who denounced Tree in favor of William Poel, Gordon Craig, and Harley Granville-Barker.