bluuebunny/crossref_metadata_2025 huggingface dataset:
The G protein–coupled receptor P2RY8 and follicular dendritic cells promote germinal center confinement of B cells, whereas S1PR3 can contribute to their dissemination
Authors: Muppidi Jagan R. , Lu Erick , Cyster Jason G.
Published: November 2015

The orphan Gα13-coupled receptor P2RY8 is mutated in human germinal center (GC)–derived lymphomas and was recently found to promote B cell association with GCs in a mouse model. Here we establish that P2RY8 promotes clustering of activated B cells within follicles in a follicular dendritic cell (FDC)–dependent manner. Although mice lack a P2RY8 orthologue, we show that mouse GC B cell clustering is also dependent on FDCs acting to support the function of a Gα13-coupled receptor. Mutations in GNA13 and its downstream effector ARHGEF1 are associated with the development of disseminated GC-derived lymphomas. We find that egress of Gna13 mutant GC B cells from lymph nodes in the mouse depends on sphingosine-1-phosphate receptor-3. These findings provide evidence that FDCs promote GC confinement of both human and mouse GC B cells via Gα13-dependent pathways, and they show that dissemination of Gα13-deficient GC B cells additionally requires an egress-promoting receptor.
Asymmetric protonation of EmrE
Authors: Morrison Emma A. , Robinson Anne E. , Liu Yongjia , Henzler-Wildman Katherine A.
Published: November 2015

The small multidrug resistance transporter EmrE is a homodimer that uses energy provided by the proton motive force to drive the efflux of drug substrates. The pKa values of its “active-site” residues—glutamate 14 (Glu14) from each subunit—must be poised around physiological pH values to efficiently couple proton import to drug export in vivo. To assess the protonation of EmrE, pH titrations were conducted with 1H-15N TROSY-HSQC nuclear magnetic resonance (NMR) spectra. Analysis of these spectra indicates that the Glu14 residues have asymmetric pKa values of 7.0 ± 0.1 and 8.2 ± 0.3 at 45°C and 6.8 ± 0.1 and 8.5 ± 0.2 at 25°C. These pKa values are substantially increased compared with typical pKa values for solvent-exposed glutamates but are within the range of published Glu14 pKa values inferred from the pH dependence of substrate binding and transport assays. The active-site mutant, E14D-EmrE, has pKa values below the physiological pH range, consistent with its impaired transport activity. The NMR spectra demonstrate that the protonation states of the active-site Glu14 residues determine both the global structure and the rate of conformational exchange between inward- and outward-facing EmrE. Thus, the pKa values of the asymmetric active-site Glu14 residues are key for proper coupling of proton import to multidrug efflux. However, the results raise new questions regarding the coupling mechanism because they show that EmrE exists in a mixture of protonation states near neutral pH and can interconvert between inward- and outward-facing forms in multiple different protonation states.
The casposon-encoded Cas1 protein from Aciduliprofundum boonei is a DNA integrase that generates target site duplications
Authors: Hickman Alison B. , Dyda Fred
Published: November 2015

Many archaea and bacteria have an adaptive immune system known as CRISPR which allows them to recognize and destroy foreign nucleic acid that they have previously encountered. Two CRISPR-associated proteins, Cas1 and Cas2, are required for the acquisition step of adaptation, in which fragments of foreign DNA are incorporated into the host CRISPR locus. Cas1 genes have also been found scattered in several archaeal and bacterial genomes, unassociated with CRISPR loci or other cas proteins. Rather, they are flanked by nearly identical inverted repeats and enclosed within direct repeats, suggesting that these genetic regions might be mobile elements (‘casposons’). To investigate this possibility, we have characterized the in vitro activities of the putative Cas1 transposase (‘casposase’) from Aciduliprofundum boonei. The purified Cas1 casposase can integrate both short oligonucleotides with inverted repeat sequences and a 2.8 kb excised mini-casposon into target DNA. Casposon integration occurs without target specificity and generates 14–15 basepair target site duplications, consistent with those found in casposon host genomes. Thus, Cas1 casposases carry out similar biochemical reactions as the CRISPR Cas1-Cas2 complex but with opposite substrate specificities: casposases integrate specific sequences into random target sites, whereas CRISPR Cas1-Cas2 integrates essentially random sequences into a specific site in the CRISPR locus.
Realization
Authors: Baysan Umut
Published: November 2015

“Realization” is a technical term used by philosophers of mind, philosophers of science, and metaphysicians to denote some dependence relation that is thought to exist between higher-level properties or states and lower-level properties or states. Some philosophers of mind hold that mental properties, such as believing that it is raining, having a painful sensation, and so on, are realized by physical properties. Understood this way, the term was introduced to philosophy of mind literature with the thesis that mental properties are multiply realizable by physical properties. Since different physical properties could realize the same mental property, it is thought that the phenomenon of multiple realization shows that the identity theory, namely the view that mental properties are identical with physical properties, is false. For similar reasons, some philosophers of the special sciences think that higher-level properties, such as biological properties, are realized by properties that are invoked in lower-level sciences such as physics. Some metaphysicians suggest that determinable properties, such as color properties (e.g., being red) are realized by their determinate properties (e.g., being crimson, being scarlet). Some argue that dispositional properties, such as being fragile, are realized by non-dispositional, categorical microstructural properties. It has been customary to think that functional properties, such as being a carburetor, are realized by first-order properties that play the specified functional roles. Due to the widely different usages of “realization,” it is difficult to determine if there should be one relation or several relations that this term denotes. Any relation that is denoted by this term can be seen as a realization relation. This article is about such relations. Whereas some theories explicitly formulate realization relations, some tangential theories that concern related issues (e.g., the mind-body problem) make crucial claims as to what counts as a case of realization. This article introduces the central questions about realization and clarifies the main issues and concepts that are invoked in the relevant literature.
Lucretius
Authors: Kennedy Duncan F.
Published: November 2015

The De rerum natura (usually translated as On the Nature of Things or On the Nature of the Universe) is a Latin poem in six books composed in the mid-1st century bce by Titus Lucretius Carus to introduce a Roman audience to the philosophy of the Greek materialist thinker Epicurus (341–270 bce). The loss of much of Epicurus’s own output means that Lucretius has become the most important source for Epicurean philosophy, but the creative transformation of that philosophy in Lucretius’s poem has left its distinctive mark on the reception of Epicurean physics and ethics in the Western materialist tradition. Virtually nothing is known of Lucretius himself, and little can be reliably inferred about him from the poem. The sole contemporary reference to the poet and his poem comes in a letter of Cicero to his brother from February 54 bce in which Cicero (a critic of Epicureanism in his own philosophical writings) echoes his brother’s marked admiration for its literary qualities. That admiration is echoed in the Roman literary tradition, but the poem’s impassioned rejection of the notions of divine creation of (or intervention in) the world, and of life after death made it a repeated target in later centuries for Christian polemic. This may underlie the biographical tradition attested in Late Antiquity (though now largely rejected) of the poet’s suicide, driven mad by a love potion. The poem was effectively unknown for a millennium after the fall of the western Roman Empire, but following the rediscovery and copying of a manuscript by the humanist Poggio Bracciolini in 1417, it has played an important and continuing role in the history of ideas and theories of materialism. It became the chief vehicle for the dissemination of ancient atomism in Renaissance and early modern thought as well as a focus or proxy for anticreationist views and a precursor of some aspects of evolutionary theory. In the modern period, its views on atomic motion (particularly the swerve of atoms), and its arguments against the fear of death continue to be invoked to frame debate, while its self-conscious response to the challenge of transmitting ideas across time, and the boundaries of language and culture, address the relationship of language and philosophy.
Pacifism
Authors: Fiala Andrew
Published: November 2015

Pacifism is a contested term. It is often defined narrowly as opposition to war, or more broadly understood as opposition to all violence. Pacifists are also sometimes committed to nonviolence as a way of life and to a vision of peaceful and harmonious coexistence. Pacifism can extend toward a commitment to nonviolence in all aspects of life, including vegetarianism. Or pacifism can be narrowly construed as an antiwar position understood at the level of political theory. Pacifism has been defended in a variety of ways: by appeal to religious authority, by grounding in fundamental moral principles, and by empirical claims about the negative consequences of violence and war. As a positive commitment to nonviolence, pacifists have argued that nonviolent social activism is both beneficial and morally praiseworthy. Pacifism has deep roots in the world’s religious traditions. In Christianity it can be traced to the Sermon on the Mount, where Jesus says, “Do not resist an evil person” and “turn the other cheek” (Matthew 5:39). Buddhism, Jainism, and other traditions have a similar emphasis on nonviolence. Religious pacifism is central to ideas found in Tolstoy, Gandhi, and Martin Luther King Jr. Philosophical discussions of pacifism can found in the work of Erasmus, Rousseau, and other post-Renaissance and Enlightenment thinkers. In more recent history, versions of pacifism have been defended by William James, Jane Addams, Bertrand Russell, and Albert Einstein. Contemporary discussions in the philosophical literature proliferated during and after the Vietnam War era, as conscientious objection became an issue. In applied ethics literature, pacifists and philosophers sympathetic to pacifism such as Cheyney Ryan, Robert Holmes, and Andrew Fiala have responded in various ways to critiques of pacifism offered by Narveson and others, while also seeking to clarify and criticize “just war” theory. Recent discussions of pacifism have emphasized the varieties of pacifism, arguing that pacifism is not merely an absolutist moral prohibition against violence. Some have defended pacifism as a merely personal or vocational commitment. Others have clarified that pacifism is primarily an antiwar position that does not necessarily extend to a critique of all violence. Others have defended varieties of practical pacifism, contingent pacifism, or pacifism grounded in just war theory—as well as articulating connections between pacifism and other issues: feminism, animal welfare, ecology, and theology. The theoretical investigation of pacifism can be supplemented by empirical work that shows that nonviolence can be an effective force for social and political change.
Presidential Persuasion and Public Opinion
Authors: Eshbaugh-Soha Matthew
Published: November 2015

Presidential persuasion is a central feature of presidential power and leadership. Although originally conceived of as essential for bargaining with and influencing Congress and later the bureaucracy, the rise of television and polling science—along with the constraints imposed by legislative gridlock and divided government—afforded presidents regular opportunities to appeal to the public to achieve their policy goals. Despite some scholarly allegations that presidents should persuade the public, the White House’s own expectations that presidents can do so, and the extent to which the modern White House polls and attempts to influence news coverage and public opinion, the predominant conclusion of the literature is that presidential persuasion is unlikely to change public opinion. Even evidence that supports presidential persuasion may be marginal, mixed, time bound, or vary by domestic and foreign policy. At times, presidents may not be able to lead public opinion because they have responded to it. And even the act of speaking, as expressed by scholars of the rhetorical presidency, may puff up unrealistic expectations for the occupant of the office. Nevertheless, presidents may be able to influence the public’s agenda on issues not previously salient to the American people, prime favorable aspects of their policies through speechmaking, and act strategically to parlay existing public support into legislative victories.
Cuban Political Development
Authors: Domínguez Jorge I.
Published: November 2015

Before dawn on 1 January 1959, President Fulgencio Batista fled Cuba. Insurgents led by Fidel Castro (one among several insurgent groups) soon established control over the national territory. Fidel Castro served as Cuba’s prime minister and then also as president of the Council of State from 1959 until 2006. His brother Raúl Castro succeeded him; in 2018, he stepped down from his government roles while remaining first secretary of the Communist Party. The ruling teams have changed only very gradually—six of the seventeen-member Political Bureau chosen at the Sixth Communist Party Congress, held in 2016, had eight members born in 1945 or earlier, the first time this older group ceded the Political Bureau majority, and nine born between 1958 and 1967. The years since 1959 encompass four periods. The first, the revolutionary decade of the 1960s, endeavored to transform many aspects of public life and private behavior, in a context of a failing economy, under Fidel Castro’s highly personalized rule. The second, during the 1970s and 1980s, featured the development of the Communist Party and state institutions akin to those prevalent in other communist countries, more orthodox central planning of the economy, with strong backing and funding from the Soviet Union, as well as the deployment of hundreds of thousands of Cuban troops and civilians overseas. The third, following the collapse of the Soviet Union, during the 1990s until 2006, exhibited a painful adjustment to greatly diminished economic circumstances and a mixed strategy to enact policy changes, some reminiscent of the 1960s and others pointing toward a market-oriented opening. The fourth, since 2006 under Raúl Castro’s leadership as Communist Party first secretary, adding since 2018 Miguel Díaz-Canel as president of the republic, has been marked by a gradual, albeit still limited, shift toward market-oriented policies and limited elements of political liberalization along with a tilt toward collective leadership and planned political succession. Across the four time periods, noteworthy changes have occurred in the economy, polity, and society, as well as in Cuba’s international circumstances.
Shamanism
Authors: Pollock Donald
Published: November 2015

Shamanism has been regarded as one of the world’s oldest religions as well as one of its newest; evidence of shamanic practice has been found in Paleolithic cave art, and shamanic experiences are being cultivated in contemporary societies, especially in its “New Age” or neoshamanism variations. The narrowest conceptions of shamanism restrict the use of the term to a specific form of religious practice found in Siberia, where the Tungus religious practitioner called šamán provided the model; Mircea Eliade’s classic study of shamanism (see Eliade 1964, cited under History of Shamanism and Shamanism Studies) grants historical and conceptual priority to this form of belief and practice, and traces its spread from those Siberian roots. Alternatively, it has been argued that the concept of shamanism should be extended to a nearly universal set of beliefs about spirits, spiritism, and occult realms. Bean 1992, for example (cited under North American and Native American Shamanism), comments that “Shamanism is the religion of all hunting and gathering cultures, and it forms the basis of many more formalized religions that retain shamanistic elements” (p. 8). Anthropologists have often adopted this broader perspective, seeking similarities among overtly different traditions typically by linking them according to the social functions served by shamans (e.g., healing through spirit intervention, community protection from malign spirit attack, and the pursuit of community political goals through the medium of spiritism). This bibliography adopts the relatively broad view that “shamanism” is a useful concept to describe a set of religious phenomena of historical depth and wide ethnographic extent, and that there is value in considering how a range of beliefs and practices are related to a basic set of defining characteristics, along with their relationship to other social and cultural phenomena. “Shamanism” has been recently described as a form of interaction between a practitioner and spirits, one that is not available to other members of a community; the practitioner (a “shaman”) acts on behalf of that community—or on behalf of individual members of that community—to perform a variety of social roles that may include healing as well as harming, affecting the outcome of subsistence activities, and so on, by intervention with spirits or through knowledge gained by communication with spirits (see Webb 2013 under the Nature of Shamanism, p. 62). As such, shamans are found in a variety of cultures that are not traditionally associated with the concept, for example as spirit mediums in sub-Saharan Africa and through spirit possession in East Asia. This bibliography considers these themes through sections on the history of the concept itself, studies of the nature of shamanism, and analyses of shamanism in various cultures around the world.
Conversational Implicature
Authors: Sperlich Darcy
Published: November 2015

The theory of conversational implicature originates from Gricean pragmatics, involving concepts of the cooperative principle, maxims of conversation and their properties, to generalized and particularized implicatures, among others. The theory’s originator, Paul Grice, delivered his ideas at the William James lectures at Harvard University in 1967. This revolutionized the direction of pragmatics and opened new frontiers of research in linguistics and beyond. The theory of conversational implicature, a cornerstone of Grice’s thinking, aims to capture how language is used in communication to maximum effect while being efficient as possible. Since Grice’s proposal, a new generation of Gricean theorists has advanced the theory, while others have taken issue with Gricean explanations and moved to create other theoretical models of meaning, such as Relevance theory. Overall, this article is separated into two distinct parts. The first part is a review of Gricean theory and its evolution into the neo-Gricean framework, with a selection of key articles and books. This is followed by an overview of post-Gricean approaches, theories that compete with Gricean conversational implicature. The second part of the article attempts to bring together the wide-ranging applications of conversational implicature to different fields. This not only includes linguistics and its subfields but also areas such as business and literature.
Impact of Null Polyphenol Oxidase Alleles on White Salted Noodles
Authors: Hystad Steven M. , Giroux Michael J. , Martin John M.
Published: November 2015

Polyphenol oxidase (PPO) causes Asian noodles to lose their bright color over time. Null Ppo‐A1 and Ppo‐D1 alleles are available that confer very low kernel PPO levels. Our goal was to characterize the effect of the Ppo‐A1i and Ppo‐D1f null alleles on the color and texture profile of white salted noodles. A white‐seeded spring wheat carrying Ppo‐A1i/Ppo‐A2d and Ppo‐D1f was crossed to a hard white‐seeded isoline of Choteau spring wheat with Ppo‐A1b/Ppo‐A2a and Ppo‐D1b and to a hard white‐seeded isoline of Vida spring wheat with Ppo‐A1a/Ppo‐A2b and Ppo‐D1b. Resultant lines homozygous for the null‐Ppo alleles or for the alternate parent Ppo alleles were selected and grown in replicated trials. The null‐Ppo alleles had no detrimental effects on kernel or flour traits. Noodles prepared from straight‐grade or whole wheat flour from the null‐Ppo allele class were less cohesive and softer than noodles from the alternate parent Ppo allele class for the White Choteau but not the White Vida population. Noodles prepared from straight‐grade and whole wheat flour from the null‐Ppo class were brighter, more red, and more yellow after 24 h and showed less change in L* with time than noodles prepared from the alternate parent Ppo class. The relative difference between the two genotype classes for change in L* with time (0–24 h) exceeded 3.5 L* for noodles from both types of flour, which was an improvement over existing low‐Ppo alleles. Incorporating the null‐Ppo alleles into wheat varieties could improve the color profile of Asian noodles.
Effects of Different Lipase Inactivation Treatments on Physicochemical Properties of Naked Oat Globulins
Authors: Gao Yichao , Wang Lili , Qiu Ju , Bai Guangling , Li Zaigui
Published: November 2015

Lipase inactivation is an essential treatment for oat processing, because of the negative effects of lipase on nutrient preservation and storage extension. The effects of different lipase inactivation treatments including hot air roasting, infrared roasting, normal‐pressure steaming, and high‐pressure steaming on the physicochemical properties of oat globulins were investigated. Results showed that normal‐pressure steaming had little effect on solubility of oat globulins; hot air roasting increased foaming capacity of oat globulins but did not change their foaming stability; and all the inactivation treatments increased the surface hydrophobicity and content of total sulfhydryls of oat globulin but decreased exposed sulfhydryl groups. In addition, oat globulin granules from the hot air roasting treatment were distributed more evenly in oat globulin powder compared with the control group. All treatments except normal‐pressure steaming changed the molecular weight of oat globulin subunits, which made the bands of 66,000 and 45,000 disappear from SDS‐PAGE. These results indicated that normal‐pressure steaming was ideal to maintain good solubility of oat globulins, and hot air roasting was ideal to maintain relatively good foaming properties. The treatments changed physicochemical properties of oat globulins by influencing protein aggregation and subunit composition that resulted in different content of sulfhydryl groups and surface hydrophobicity.
Inhibition of Grape Crown Gall byAgrobacterium vitisF2/5 Requires Two Nonribosomal Peptide Synthetases and One Polyketide Synthase
Authors: Zheng Desen , Burr Thomas J.
Published: November 2015

Agrobacterium vitis nontumorigenic strain F2/5 is able to inhibit crown gall disease on grapevines. The mechanism of grape tumor inhibition (GTI) by F2/5 has not been fully determined. In this study, we demonstrate that two nonribosomal peptide synthetase (NRPS) genes (F-avi3342 and F-avi5730) and one polyketide synthase gene (F-avi4330) are required for GTI. Knockout of any one of them resulted in F/25 losing GTI capacity. We previously reported that F-avi3342 and F-avi4330 but not F-avi5730 are required for induction of grape tissue necrosis and tobacco hypersensitive response. F-avi5730 is predicted to encode a single modular NRPS. It is located in a cluster that is homologous to the siderophore vicibactin biosynthesis locus in Rhizobium species. Individual disruption of F-avi5730 and two immediate downstream genes, F-avi5731 and F-avi5732, all resulted in reduced siderophore production; however, only F-avi5730 was found to be required for GTI. Complemented F-avi5730 mutant (ΔF-avi5730+) restored a wild-type level of GTI activity. It was determined that, over time, populations of ΔF-avi4330, ΔF-avi3342, and ΔF-avi5730 at inoculated wound sites on grapevine did not differ from those of ΔF-avi5730+indicating that loss of GTI was not due to reduced colonization of wound sites by mutants.
Wheat Blast and Fusarium Head Blight Display Contrasting Interaction Patterns on Ears of Wheat Genotypes Differing in Resistance
Authors: Ha Xia , Koopmann Birger , von Tiedemann Andreas
Published: November 2015

The interaction of wheat with two ear pathogens, Magnaporthe wheat blast (MWB) and Fusarium graminearum (Fusarium head blight, FHB), was studied on the phenotypic, histological, and gene expression level. Most of the 27 wheat cultivars inoculated with MWB and F. graminearum displayed inverse disease responses to blast and FHB infection. Two cultivars, Milan and Sumai 3, were selected expressing converse disease phenotypes to blast (Milan, R)/(Sumai 3, S) and FHB (Milan, S)/(Sumai 3, R). Confocal laser scanning microscopy revealed early (12 h postinoculation) colonization of the spikelets by MWB similarly on both cultivars, while F. graminearum infected anthers of the susceptible cultivar earlier. Both pathogens grew much faster in the rachilla of susceptible than resistant cultivars, indicating that resistance is mainly expressed in this part connecting the spikelet with the rachis. In general, O2− and H2O2 levels were unrelated to disease expression in the four studied interactions. The differential disease phenotypes, fungal spread in the rachis, and colonization patterns in the spikelets were confirmed by distinct gene expression patterns. Among the eight genes analyzed, seven were more strongly induced by FHB than by blast. Genes for chitinase (Chi2), β-1,3-glucanase (PR2), a plant defensin homolog (PRPI), and peroxidase (Pox2) were strongly upregulated in Milan in response to both pathogens, while PR2 and PR5 (thaumatin-like protein) were transiently triggered by MWB on both cultivars. Upregulation of cinnamoyl-CoA reductase (CCR), cytochrome P450 (CYP709C1), and UDP-glycosyl transferase (UGT) were more prominent in ears infected with F. graminearum, while upregulation of UGT was higher in Sumai 3 when infected with either pathogen. Cultivar resistance to FHB was reflected by clearly higher expression levels of UGT and CYP709C1 in Sumai 3. The differential responses of wheat to the two ear pathogens demonstrated in this study makes it unlikely that common resistance genes exist for control of FHB and blast, suggesting the need to stack many genes associated with resistance in breeding programs for multiple resistance.
Development and Deployment of Systems-Based Approaches for the Management of Soilborne Plant Pathogens
Authors: Chellemi D. O. , Gamliel A. , Katan J. , Subbarao K. V.
Published: November 2015

Biological suppression of soilborne diseases with minimal use of outside interventive actions has been difficult to achieve in high input conventional crop production systems due to the inherent risk of pest resurgence. This review examines previous approaches to the management of soilborne disease as precursors to the evolution of a systems-based approach, in which plant disease suppression through natural biological feedback mechanisms in soil is incorporated into the design and operation of cropping systems. Two case studies are provided as examples in which a systems-based approach is being developed and deployed in the production of high value crops: lettuce/strawberry production in the coastal valleys of central California (United States) and sweet basil and other herb crop production in Israel. Considerations for developing and deploying system-based approaches are discussed and operational frameworks and metrics to guide their development are presented with the goal of offering a credible alternative to conventional approaches to soilborne disease management.
Revision Forefoot: Technique for Salvage After First Metatarsophalangeal Joint Arthroplasty With Arthrodesis
Authors: Jackson Lyle , Roster Brent , Kreulen Christopher , Giza Eric
Published: November 2015

Failure of a first metatarsophalangeal joint arthroplasty can be a debilitating condition for the patient and a challenging condition for the treating surgeon. This technique article highlights 2 techniques: the use of a tricortical iliac crest bone block allograft and also distal tibia autograft for metatarsophalangeal joint arthrodesis and management of the bony defect.

Level of Evidence: Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Overexpression of Carbonic Anhydrase IX is a Dismal Prognostic Marker in Breast Carcinoma in Egyptian Patients
Authors: Samaka Rehab M. , Abd El-Wahed Moshira M. , Al Sharaky Dalia R. , Shehata Mohamed A. , Hegazy Shaymaa E. , Aleskandarany Mohammed A.
Published: November 2015

Carbonic anhydrase IX (CAIX) is an enzyme whose expression is very limited in normal tissues and it is highly expressed in various cancers. Therefore, inhibition of CAIX is considered as a promising therapeutic target for the treatment of solid tumors where hypoxic environment has developed. The aim of the current work is to evaluate the immunohistochemical (IHC) expression of CAIX in breast cancer (BC) of Egyptian patients and to investigate the associations of CAIX expression with the standard clinicopathologic features, IHC subtypes of BC, and overall survival. This retrospective study was conducted on 56 archival cases of Egyptian BC patients. Fifty-one of 56 cases (91.1%) showed positive expression of CAIX with cytoplasmic localization, whereas 5 cases (8.9%) showed negative expression. CAIX IHC overexpression is significantly associated with advanced stage and presence of coagulative tumor cell necrosis (P=0.03 and 0.02, respectively). Multivariate analysis revealed Ki67 labeling index and CAIX H-score grouping (P=0.03 and 0.02, respectively) as independent prognostic factors affecting BC patients’ overall survival. We concluded that CAIX could play a role in the progression of the studied BC cases. CAIX is a good candidate for target therapy.
Human Papillomavirus (HPV) Detection in Cytologic Specimens: Similarities and Differences of Available Methodology
Authors: Bihl Michel P. , Tornillo Luigi , Kind André B. , Obermann Ellen , Noppen Christoph , Chaffard Rosemarie , Wynne Patricia , Grilli Bruno , Foerster Anja , Terracciano Luigi M. , Hoeller Sylvia
Published: November 2015

Accumulating evidence regarding the causative role of human papillomavirus (HPV) in a wide range of malignant and nonmalignant diseases highlights the importance of HPV testing. This study describes and discusses the efficacy and characteristics of 4 well-established and commercially available tests. Here, 181 cytologic specimens from cervical smears were analyzed using the HPV SIGN PQ (Diatech) and the Linear Array (Roche) method. Discrepant results were further studied with the Real Time High-Risk HPV (Abbott) method and the INNO-LiPA (Fujirebio) method. Of 181 cytologic specimens, 61 (34%) showed discrepant results. High-risk HPV was not detected in 9 cases by HPV SIGN PQ, in 16 cases by Linear Array, in 10 cases by Real Time High-Risk HPV, and in 6 cases by INNO-LiPA, respectively. Lack of DNA detection or problems in interpreting the result were seen in 9 cases with HPV SIGN PQ, 8 cases with Linear Array, 3 cases with Real Time High-Risk HPV, and 3 cases with INNO-LiPA, respectively. This study indicates that the choice of HPV detection method has a substantial influence on the HPV risk classification of tested PAP smears and clinical follow-up decisions.
Fumarate Hydratase–deficient Uterine Leiomyomas Occur in Both the Syndromic and Sporadic Settings
Authors: Harrison Wesley J. , Andrici Juliana , Maclean Fiona , Madadi-Ghahan Raha , Farzin Mahtab , Sioson Loretta , Toon Christopher W. , Clarkson Adele , Watson Nicole , Pickett Justine , Field Michael , Crook Ashley , Tucker Katherine , Goodwin Annabel , Anderson Lyndal , Srinivasan Bhuvana , Grossmann Petr , Martinek Petr , Ondič Ondrej , Hes Ondřej , Trpkov Kiril , Clifton-Bligh Roderick J. , Dwight Trisha , Gill Anthony J.
Published: November 2015

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome secondary to germline fumarate hydratase (FH) mutation presents with cutaneous and uterine leiomyomas, and a distinctive aggressive renal carcinoma. Identification of HLRCC patients presenting first with uterine leiomyomas may allow early intervention for renal carcinoma. We reviewed the morphology and immunohistochemical (IHC) findings in patients with uterine leiomyomas and confirmed or presumed HLRCC. IHC was also performed on a tissue microarray of unselected uterine leiomyomas and leiomyosarcomas. FH-deficient leiomyomas underwent Sanger and massively parallel sequencing on formalin-fixed paraffin-embedded tissue. All 5 patients with HLRCC had at least 1 FH-deficient leiomyoma: defined as completely negative FH staining with positive internal controls. One percent (12/1152) of unselected uterine leiomyomas but 0 of 88 leiomyosarcomas were FH deficient. FH-deficient leiomyoma patients were younger (42.7 vs. 48.8 y, P=0.024) and commonly demonstrated a distinctive hemangiopericytomatous vasculature. Other features reported to be associated with FH-deficient leiomyomas (hypercellularity, nuclear atypia, inclusion-like nucleoli, stromal edema) were inconstantly present. Somatic FH mutations were identified in 6 of 10 informative unselected FH-deficient leiomyomas. None of these mutations were found in the germline. We conclude that, while the great majority of patients with HLRCC will have FH-deficient leiomyomas, 1% of all uterine leiomyomas are FH deficient usually due to somatic inactivation. Although IHC screening for FH may have a role in confirming patients at high risk for hereditary disease before genetic testing, prospective identification of FH-deficient leiomyomas is of limited clinical benefit in screening unselected patients because of the relatively high incidence of somatic mutations.
Identification of genes related to learning and memory in the brain transcriptome of the mollusc,Hermissenda crassicornis
Authors: Tamvacakis Arianna N. , Senatore Adriano , Katz Paul S.
Published: November 2015

The sea slugHermissenda crassicornis(Mollusca, Gastropoda, Nudibranchia) has been studied extensively in associative learning paradigms. However, lack of genetic information previously hindered molecular-level investigations. Here, theHermissendabrain transcriptome was sequenced and assembled de novo, producing 165,743 total transcripts. Orthologs of 95 genes implicated in learning were identified. These included genes for a serotonin receptor and a GABA-B receptor subunit that had not been previously described in molluscs, as well as an adenylyl cyclase gene not previously described in gastropods. This study illustrates theHermissendatranscriptome's potential as an important genetic tool in future learning and memory research.
mTOR is essential for corticosteroid effects on hippocampal AMPA receptor function and fear memory
Authors: Xiong Hui , Cassé Frédéric , Zhou Yang , Zhou Ming , Xiong Zhi-Qi , Joëls Marian , Martin Stéphane , Krugers Harm J.
Published: November 2015

Glucocorticoid hormones, via activation of their receptors, promote memory consolidation, but the exact underlying mechanisms remain elusive. We examined how corticosterone regulates AMPA receptors (AMPARs), which are crucial for synaptic plasticity and memory formation. Combining a live imaging fluorescent recovery after photobleaching approach with the use of the pH-sensitive GFP-AMPAR tagging revealed that corticosterone enhances the AMPAR mobile fraction and increases synaptic trapping of AMPARs in hippocampal cells. In parallel, corticosterone-enhanced AMPAR-mediated synaptic transmission. Blocking the mammalian target of rapamycin (mTOR) pathway prevented the effects of corticosterone on both AMPAR trapping—but not on the mobile fraction—and synaptic transmission. Blocking the mTOR pathway also prevented the memory enhancing effects of corticosterone in a contextual fear-conditioning paradigm. We conclude that activation of the mTOR pathway is essential for the effects of corticosterone on synaptic trapping of AMPARs and, possibly as a consequence, fearful memory formation.
Compound stimulus extinction reduces spontaneous recovery in humans
Authors: Coelho Cesar A.O. , Dunsmoor Joseph E. , Phelps Elizabeth A.
Published: November 2015

Fear-related behaviors are prone to relapse following extinction. We tested in humans a compound extinction design (“deepened extinction”) shown in animal studies to reduce post-extinction fear recovery. Adult subjects underwent fear conditioning to a visual and an auditory conditioned stimulus (CSA and CSB, respectively) separately paired with an electric shock. The target CS (CSA) was extinguished alone followed by compound presentations of the extinguished CSA and nonextinguished CSB. Recovery of conditioned skin conductance responses to CSA was reduced 24 h after compound extinction, as compared with a group who received an equal number of extinction trials to the CSA alone.
The cannabinoid system in the retrosplenial cortex modulates fear memory consolidation, reconsolidation, and extinction
Authors: Sachser Ricardo Marcelo , Crestani Ana Paula , Quillfeldt Jorge Alberto , Mello e Souza Tadeu , de Oliveira Alvares Lucas
Published: November 2015

Despite the fact that the cannabinoid receptor type 1 (CB1R) plays a pivotal role in emotional memory processing in different regions of the brain, its function in the retrosplenial cortex (RSC) remains unknown. Here, using contextual fear conditioning in rats, we showed that a post-training intra-RSC infusion of the CB1R antagonist AM251 impaired, and the agonist CP55940 improved, long-term memory consolidation. Additionally, a post-reactivation infusion of AM251 enhanced memory reconsolidation, while CP55940 had the opposite effect. Finally, AM251 blocked extinction, whereas CP55940 facilitated it and maintained memory extinguished over time. Altogether, our data strongly suggest that the cannabinoid system of the RSC modulates emotional memory.
Crystal structure of 1-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-2-(thiazol-4-yl)-1H-benzimidazole
Authors: Gueddar Hicham , Bouhfid Rachid , Essassi El Mokhtar , Saadi Mohamed , El Ammari Lahcen
Published: November 2015

The benzimidazole ring in the title compound, C16H17N3O2S, is almost planar, with the greatest deviation from the mean plane being 0.032 (1) Å. The fused-ring system makes dihedral angles of 19.91 (7) and 24.51 (8)° with the best plane through each of the thiazol-4-yl and 1,3-dioxolan-4-yl rings, respectively; the latter exhibits an envelope conformation with the methylene C atom being the flap. Finally, the thiazol-4-yl ring makes a dihedral angle of 33.85 (9)° with the 1,3-dioxolan-4-yl ring. In the crystal, molecules are connected by a pair of C—H...π(imidazole) interactions to form centrosymmetric aggregates.
Crystal structures of two bis(iodomethyl)benzene derivatives: similarities and differences in the crystal packing
Authors: McAdam C. John , Hanton Lyall R. , Moratti Stephen C. , Simpson Jim
Published: November 2015

The isomeric derivatives 1,2-bis(iodomethyl)benzene, (I), and 1,3-bis(iodomethyl)benzene (II), both C8H8I2, were prepared by metathesis from their dibromo analogues. Theortho-derivative, (I), lies about a crystallographic twofold axis that bisects the C—C bond between the two iodomethyl substituents. The packing in (I) relies solely on C—H...I hydrogen bonds supported by weak parallel slipped π–π stacking interactions [inter-centroid distance = 4.0569 (11) Å, inter-planar distance = 3.3789 (8) Å and slippage = 2.245 Å]. While C—H...I hydrogen bonds are also found in the packing of (II), type II, I...I halogen bonds [I...I = 3.8662 (2) Å] and C—H...π contacts feature prominently in stabilizing the three-dimensional structure.
Crystal structure of hexaprop-2-en-1-yl 4,4′,4′′,4′′′,4′′′′,4′′′′′-[1,3,5,2λ5,4λ5,6λ5-triazatriphosphinine-2,2,4,4,6,6-hexaylhexakis(oxy)]hexabenzoate
Authors: Zhu Jing , Li Qian , Zheng Fu-Wei , He Juan , Qu Ling-Bo
Published: November 2015

In the title compound, C60H54N3O18P3, the central phosphazene ring is essentially planar, with an r.m.s. deviation of the six fitted atoms of 0.068 Å. The P—N bond lengths are within the narrow range 1.575 (2)–1.585 (2) Å, indicating the electrons are delocalized within the ring. The two ethenyl benzoate substituents on each P atom are located up and down with respect to the plane of the central P3N3ring. The atoms of two terminal propenyl groups are disordered over two sets of sites, with refined site-occupancy ratios of 0.249 (12):0.751 (12) and 0.476 (9):0.524 (9). No intermolecular interactions are observed.
Welfare gains, risk-sharing and Africa’s monetary union projects
Authors: Nnyanzi John Bosco
Published: November 2015

Purpose

– The purpose of this paper is to investigate the welfare gains from risk sharing among African countries and regional groupings in Africa that are planning to establish monetary unions either in the short or longrun.

Design/methodology/approach

– The paper empirically tested two hypothesis; potential welfare gains and unexploited welfare gains. It uses a utility-based measure to quantify the gains that would accrue from joining a risk sharing arrangement such as a monetary union. The regional groupings considered include the African Union (AU), the Economic Community of West Africa (ECOWAS), the Southern African Development Community (SADC) and the East African Community (EAC).

Findings

– The results provide support for both hypotheses. Overall, the average potential welfare for AU, EAC, ECOWAS and SADC groups under full risk sharing are found to be 1.9, 2, 3.4 and 1.6 percent, respectively, each higher than the 1 percent estimated for the OECD countries and 0.6 percent for the 14-EU countries. The average unexploited gains are, however, even bigger for AU at 3.5 percent, ECOWAS at 8.6 percent and for SADC at 2.6 percent.

Practical implications

– The finding of enormous potential welfare gains could partly reinforce the desire of the African countries to establish monetary unions. On the other hand, the paper provides insights to policy makers in designing policies to promote risk sharing given the finding that the unexploited welfare gains are on average still too low – implying that many African countries or groups still have very low risk sharing.

Originality/value

– Previous studies on welfare gains and risk sharing have basically left out the African regional groupings and never related the issue of gains to the monetary union projects. Besides, previous studies focus on unexploited welfare gains at the expense of total potential welfare gains. Considering the two types, however, presents a more complete picture of total gains from joining any risk sharing arrangement such as a monetary union.
Does access to local markets influence child labor? Evidence from rural Uganda
Authors: Muhumuza Tony
Published: November 2015

Purpose

– The purpose of this paper is to analyze the relationship between access to rural product markets and the extent and nature of child labor. It is built on the view that if physical markets can shape rural development through, for instance, influencing prices, household production decisions, and employment, the associated activity growth could increase child labor.

Design/methodology/approach

– Using the Uganda National Household Survey, the author combines two methodological approaches: first, a probit model to estimate the probability of a child engaging in labor, and second, a double-hurdle model to analyze the hours of child work.

Findings

– The author finds that children increase time in domestic work when local product markets are distant, while their time in economic activity declines. A similar pattern is observed for the incidence of child labor. The likelihood of child labor in domestic activity increases for each extra hour of travel to the market, while child labor in economic activity declines. This could reflect the possibility that households may switch child work from market-oriented activities to domestic work when they are remotely located from markets. Results confirm findings from earlier cross-country studies that access to product markets may be detrimental to children. Second, they demonstrate that the effect of the markets varies, depending on the age of children, as well as the nature of the work they engage in.

Originality/value

– No part of this work has been published anywhere before.
Corporate social responsibility in South Africa: quo vadis?
Authors: Coldwell David Alastair Lindsay , Joosub Tasneem
Published: November 2015

Purpose

– Strategies and policies aimed at alleviating poverty in Sub-Saharan African countries usually depend on capitalistically driven economic growth. However, the view that capitalism needs to reinvent itself to survive the crisis of confidence brought about by the recent global financial collapse depends on the extent to which such a shared value oriented, sustainable capitalist reinvention is embraced by emergent business leaders. A sustainable system of capitalism driven by business and community shared value can only take root if the hearts and minds of future business leaders are convinced of their cogency and appropriateness. The paper aims to discuss these issues.

Design/methodology/approach

– This paper reports the findings of an empirical study utilizing a Likert-type scale designed to measure corporate shared value (CSV) and corporate social responsibility (CSR) among a sample of fourth year accountancy students at a leading South African university.

Findings

– Preliminary findings suggest that perceptions of this group of emergent leaders generally regard CSR rather than CSV as the “correct” business model for companies to follow. Although the sample is limited to one South African university and is relatively small, it contributes to the literature by offering insight into emergent business leaders’ perceptions and their view of the direction of CSR in South Africa should take.

Research limitations/implications

– Implications of the paper are that by offering insight into emergent business leaders’ perceptions of South African society and specifically their view of the direction South African CSR should take, the paper suggests prescriptive remedial steps in policy that educational and other learning institutions could take to engender appropriate social values in learners.

Originality/value

– The study contributes to the literature by offering devised and tested measuring instruments for CSR and CSV in the South African context and gives insight into emergent business leaders’ perceptions and their view of the direction of CSR in South Africa should take.