bluuebunny/crossref_metadata_2025 huggingface dataset:
Aesthetic Hedonism
Authors: Matthen Mohan , Weinstein Zachary
Published: April 2019

Hedonism is the view that pleasure is the only thing that has final, or non-derivative, value: other things are valuable only to the extent that they produce pleasure. In this context, pleasure may be narrowly conceived as an agreeable sensation, or functionally as a psychological response that reinforces a subject’s propensity to perform the action that evokes the response. (Critics of aesthetic hedonism [AH] have often assumed the former, but criticism narrowly based on this conception does not work when leveled against a functional conception.) Either way, it makes value depend on human response, not on objective qualities. AH applies this thesis to aesthetic value, holding that it derives from aesthetic pleasure. AH runs contrary to objectivism—the idea that aesthetic value is independent of the value of experience (experience being, at most, an apprehension of value). AH starts from the fact that human beings “like” art; aesthetic value is then understood as the instrumental value of giving them what they like. However, great tragedy arouses negative emotions, and the best art is cognitively difficult to understand. These are psychological barriers to engagement and appreciation. AH must show why these barriers do not reduce value. Most aesthetic hedonists address the difficulty by delimiting the scope either of hedonism or of aesthetic pleasure. Some scholars, e.g. Hume, say that art must be valued relative to the response of somebody who has been sufficiently exposed to it, and has thus developed “taste”; only the pleasure that such subjects take in art is probative. Others, e.g. Kant, posit a special kind of pleasure characteristic of aesthetic appreciation. This, he says, is “disinterested,” and thus different from the mere “agreeability” of food and sex, and also of low art—it is, nevertheless, a form of pleasure. In other treatments, other human motivations are invoked, including emotional immersion in Indian “rasa” theory, social harmony in Confucius, forms of eroticism (an idea that traces back to Plato), Freudian negative impulses such as the death wish, and vitalistic life forces. These are not forms of hedonism in the strict sense, but they are founded on human response, and so they are anti-objectivist in tenor. More recently, ideas from other areas of philosophy—specifically philosophy of mind and value theory—have been employed for and against AH, including nontraditional ways of understanding the nature of pleasure. The authors would like to acknowledge research support from the Australian Research Council DP 150103143 as part of the research project Taste and Community led by Jennifer A. McMahon, on which Mohan Matthen was a co-investigator.
The Division of Labor after Durkheim
Authors: Hausner Sondra L.
Published: April 2019

The “division of labor” is a concept referring to the way a society or social group organizes itself internally, but it is also used in contemporary terms to refer to Émile Durkheim’s seminal text on the subject, The Division of Labor in Society, originally published in 1893. In Durkheim’s analysis, the division of labor manifests in advanced societies such that professional groups do the work of separate sectors, and the group itself functions, it was assumed, more efficiently than if every individual had to perform every act on his or her own. The division of labor is not only the mark of an advanced society for Durkheim; he argues also that it is the very nature of social interaction, inherent in the workings of every social group and even in animal species. He suggests that the division of labor, or the separation of an organic whole into organized parts, is close to a biological imperative that enables the coherence and cohesion of a social order. Writing in the late 19th century, Durkheim does not dispute the evolutionary character of social groups, however; what differentiates different kinds of societies is the kind of division of labor they present. A primitive, or less differentiated, society relies on its relative internal sameness to produce what he calls mechanical solidarity; an advanced, or more individuated, society creates (through the difference between not only individuals but also between different subgroups, or occupational groups, within the larger social order) what he calls organic solidarity, in the sense that it may more naturally form an organic whole. The ways in which human societies come together form the mainstay of Durkheimian thought, and the discipline of sociology more generally. Durkheim’s concern with the relative strength or weakness of that social bond—always based upon the division between individuals, linked mechanically or organically—would remain the primary focus for his study of society, beginning with an analysis of difference and fragmentation in The Division of Labor in Society and moving, over the course of his intellectual development for the next two decades, to an analysis of the transcendence of those divisions. Society as a whole was understood as incorporating both individuals in their differences and social groups in their wholes: this project still grounds contemporary sociology, which attempts to understand the nature of collective formation at different levels and scales, through its analyses of solidarity and morality; law; economics and exchange; gender and the family; class and caste; and the nation, the state, and transnational forces as they respond to and produce the now global division of labor.
LGBT Social Movements
Authors: Stone Amy L. , Davis Sarah
Published: April 2019

The study of lesbian, gay, bisexual, and transgender (LGBT) social movements mostly emerges out of the sociological study of social movements, although historians have written a number of texts focusing on the history of the movement. The LGBT movement has transformed dramatically throughout time; contemporary queer politics would be incomprehensible to homophile activists mobilizing after World War II. At any given moment, the movement has diversity within it in terms of participants, agendas, tactics, and collective identities; in the early 1970s, within the one social movement there were lesbian feminists and gay liberationists organizing more radical politics, homophile activists taking more moderate approaches to visibility, and the beginnings of the modern liberal gay rights movements. Scholars tend to focus on the mobilizations, tactics, ideologies, and collective identities of the movements. This bibliography provides an overview of the LGBT movements, sections on major phases of the movement, and sections that provide guidance on law and culture in the movement. The major phases of the movement include the early gay and lesbian homophile organizing, gay liberationist politics, lesbian feminism, AIDS activism, and the modern LGBT movement.
Clara Schumann
Authors: Kregor Jonathan
Published: April 2019

Clara Schumann, née Wieck (b. 1819–d. 1896), ranks among the most important musical artists of the 19th century. As composer, she published twenty-one numbered compositions—including a piano concerto, piano trio, songs, and Lieder—in an era when it was uncommon for women to do so. As pianist, she was one of the first to consistently program the music of J. S. Bach, Ludwig van Beethoven, Johannes Brahms, and her husband, Robert Schumann. And with a career that spanned more than half a century—from her solo debut in Leipzig at the age of eleven until her death sixty-six years later in Frankfurt—she came into contact with most of the major and minor artists of the day, including Woldemar Bargiel, Frédéric Chopin, Niels Gade, Joseph Joachim, Franz Liszt, Felix Mendelssohn, Pauline Viardot-Garcia, and Richard Wagner. Yet, despite these activities and associations, prior to about the 1980s she was rarely the subject of sustained scholarly study, except in cases where she provided context for the understanding of her husband’s life and works. Since the late 1970s, however, studies have proliferated (albeit almost exclusively in English- and German-language publications), with extensive coverage devoted to her family and associates, the cities she toured and places she called home, the role(s) in which gender played in shaping her image and compositions, her composition oeuvre, her editorial and pedagogical legacy, and her posthumous reception. These studies have benefited from the appearance of critical editions of almost her entire compositional catalogue. (Note that before her marriage in 1840, she was named Clara Wieck; from 1840 onward, Clara Schumann. For consistency’s sake, this article always refers to her as “Clara Schumann,” even if the respective scholarship does not or if the topic exclusively concerns her life or activities before marriage.)
Mathematical Anthropology
Authors: Read Dwight W.
Published: April 2019

Mathematical anthropology has as its raison d’être formally expressing models, ideas, and concepts developed by anthropologists so as to extend our understanding of human societies. When addressing cultural systems, the mathematical content of mathematical anthropology depends on which of two possible ways culture is understood to be constituted. One way considers culture to consist mainly of socially learned and transmitted behaviors, and the other way considers culture to be composed of shared idea systems that provide the framework through which behavior is formulated and articulated. The first way leads to statistical modeling of behavior patterns measured over an aggregate and to quantitative and descriptive accounts of cultural system revealed through patterns of behavior. The second way involves mathematical representations aimed at working out the structural organization and generative logic of cultural idea systems. Mathematical anthropology, as it is considered here, relates to culture in this latter sense, and thus involves using mathematical representations as a way to express and work out the structural implications of the concepts forming the cultural idea systems making up the cultural milieu of a group.
The Bible and American Literature
Authors: Cook Jonathan A.
Published: April 2019

It is a critical commonplace that the King James Bible served as the moral and cultural foundation for the Reformed Protestant community—a People of the Book—that developed in Puritan and colonial America and then continued in this role in the newly established United States well into the twentieth century. Yet the contemporary student of American literature and the Bible is initially confronted with a paradox; for although commentators have long recognized the central role of the King James Bible in the development of the American literary tradition (as in the culture at large), the subject has long occupied a marginal position in the academy. As an interdisciplinary endeavor, the study of American literature and the Bible ideally requires competence in two academic realms, as manifested in the work of such past masters as Northrop Frye, Frank Kermode, Robert Alter, and Harold Bloom. Having developed in tandem with the growth of literary approaches to the Bible, the study of the influence of the Bible on American literature is now an increasingly recognized area of scholarly interest. Initially a field dominated by Christian scholars, it currently includes all those who recognize the Bible as a culturally authoritative source text for Western culture and tradition. The field has markedly expanded in recent years, with the appearance of key reference books, general surveys, and author studies. Major American writers such as Ralph Waldo Emerson, Nathaniel Hawthorne, Harriet Beecher Stowe, Walt Whitman, Herman Melville, Emily Dickinson, Mark Twain, William Faulkner, John Steinbeck, and Flannery O’Connor now have a substantial body of critical commentary on their work in relation to the Bible, while many others have received varying degrees of attention from this vibrant academic discipline.
Psychological Perspectives on Metaphor
Authors: Bowdle Brian
Published: April 2019

Metaphors are commonly defined as figures of speech in which one thing is described in terms of another thing that is notably different. For example, in the metaphor love is a rose, the target term love refers to a human emotion, whereas the source term rose refers to a flowering plant. Metaphor is classified as a type of figurative language (along with idioms, irony, metonymy, and several other forms), and until fairly recently, it was assumed that metaphors and other figures of speech were relatively unimportant aspects of communication. However, it is now recognized that metaphor is pervasive in everyday language, and a growing number of researchers and theorists now view metaphor more as an aspect of thought than of language. Indeed, metaphor has been shown to be involved in knowledge acquisition, conceptual change, abstract reasoning, social persuasion, and even the development of empathy between individuals and groups. It is hardly surprising, then, that metaphor now occupies a central place in many areas of research on cognition and communication. This article begins by listing a number of introductory volumes, anthologies, and journals devoted to metaphor and related forms of figurative language. Next, a lengthy section on theoretical approaches to metaphor processing traces the evolution of different perspectives on the nature of metaphor and discusses a range of important theories and key research studies. This is followed by a section on metaphoric framing in text and discourse, which describes both laboratory and real-world studies of how metaphor is used to structure knowledge and change attitudes. A short section on nonlinguistic and multimodal metaphors covers recent work on metaphor in gesture, visual art, music, and other domains. The next two sections describe developmental research and cognitive neuroscience research on metaphor. Finally, the last section covers practical resources for metaphor research, including guides to research methods and collections of metaphors.
Paternalistic Leadership
Authors: Pellegrini Ekin K.
Published: April 2019

Paternalistic leadership (PL) remains the leading indigenous leadership research area with increasing interest in the past three decades, and an exponential growth of research productivity in the last ten years. Paternalism in the context of leadership reflects a hierarchical relationship and is based on the assumption of power inequality. The current body of research on PL is fragmented, with research emerging from an array of different cultural contexts. While cross-cultural research interest provides an inclusive cultural base for theoretical development, it has also led to a lack of conceptual clarity, insufficient delineation of research paradigms, and inconsistent results. In the extant PL literature, two broad conceptualizations can be identified. First, there is theoretical and empirical research disseminating from Turkey, which defines PL as a hierarchical relationship in which the leader guides employees in their professional and personal lives, in a manner resembling a parent, and in return expects loyalty and deference. This definition refers to PL as a construct comprised of benevolent and authoritative leadership, common in the Middle East. Second, there is a more authoritarian definition emerging from China which suggests a configural approach and refers to PL as a combination of authoritarian, benevolent, and moral leadership. Given these two established and diverse conceptualizations, the definition of PL depends, in part, on one’s cultural context and theoretical perspective.
Geography and Class
Authors: Das Raju J.
Published: April 2019

The concept of class has been alive in the social sciences and humanities for well over a century. In geography, class was popularized in the late 1970s as Marxism was brought into the field by the likes of David Harvey and Richard Peet, and with the establishment of the journal Antipode at Clark University in Massachusetts. Geographers have approached class from the vantage point of key concepts of geographical inquiry—namely space, place, scale, and the environment. In recent decades, alongside the postmodern turn in the social sciences and humanities, research and thinking about class has been challenged by feminism and antiracist thinking, which have questioned the centrality of class in explanatory critique. It is argued that the class-centric approach to society ignores, or heavily underemphasizes, the gendered and racial dimensions of society. Given the race- and gender-based fragmentation of the working class, the class approach could not present a unified force against capitalism, so there was a need for new conceptualizations that went beyond class. Later works in this strain of thought argued that class position only matters as a site of experience and does not necessarily provide any potential for resistance. As such, the power of class as a concept has become increasingly diluted in the field, with a seeming resurgence that plateaus with the triad of oppression (race, gender, class) and the so-called method of intersectionality. More recently, debates surrounding class as a category have resurfaced in geography in relation to studies on the agency of labor, but this work has been found wanting for its voluntarism and empiricism. There is only a minority voice in geography and allied disciplines that argues for the primacy or centrality of class as it is rooted in the relation of production, and that has implications for understanding nonclass social oppression and anti-capitalist resistance.
Water Management
Authors: Nickum James E.
Published: April 2019

Nature did China few favors in its allocation of water, either spatially or seasonally. The South has abundant water but little land that is easy to cultivate, while the much drier North and Northwest have extensive plains but limited rainfall, which when it comes is concentrated strongly in the summer months, followed by long dry winters. Under these circumstances, water management in China is a holding company of wicked problems, including floods, droughts, pollution, climate impacts, hydropower development, environmental degradation, urbanization on an unprecedented scale, and, recently, international waters. It is fair to conclude that the nature and fate of the Chinese state has been linked in large degree to extensive and continuous intervention in the hydraulic cycle, both to prevent harm (shuihai水害) and to make beneficial use of water (shuili水利). Methods adopted for that intervention, discussed in separate entries in this chapter, have included dikes, irrigation, dams, interbasin transfers from water-abundant to water-scarce areas, and institutional reform. Attempts at institutional reform can themselves confront wicked problems of implementation in a polity of the size and complexity of China, with a governing system that, while changing in many ways under the People’s Republic, and especially in the recent reform period, remains one that is perhaps best characterized as one of “fragmented authoritarianism.” In the 21st century, the water needs of a globalized market economy and the growth of megacities, the exploitation of international waters (notably for hydropower), gigantic interbasin transfers, and water pollution have added to the complexity of water management, and to a fragmentation of scholarship on what falls under the expanding rubric of water management. An entrée to this expanding literature may be found in the individual sections of this bibliography.
The Impact of Culturing the Organ Preservation Fluid on Solid Organ Transplantation: A Prospective Multicenter Cohort Study
Authors: Oriol I , Sabe N , Càmara J , Berbel D , Ballesteros M A , Escudero R , Lopez-Medrano F , Linares L , Len O , Silva J T , Oliver E , Soldevila L , Pérez-Recio S , Guillem L L , Camprubí D , LLadó L , Manonelles A , González-Costello J , Domínguez M A , Fariñas M C , Lavid N , González-Rico C , Garcia-Cuello L , Arnaiz de las Revillas F , Fortun J , Aguado J M , Jimenez-Romero C , Bodro M , Almela M , Paredes D , Moreno A , Pérez-Cameo C , Muñoz-Sanz A , Blanco-Fernández G , Cabo-González J A , García-López J L , Nuño E , Carratalà J
Published: April 2019

Background

We analyzed the prevalence, etiology, and risk factors of culture-positive preservation fluid and their impact on the management of solid organ transplant recipients.

Methods

From July 2015 to March 2017, 622 episodes of adult solid organ transplants at 7 university hospitals in Spain were prospectively included in the study.

Results

The prevalence of culture-positive preservation fluid was 62.5% (389/622). Nevertheless, in only 25.2% (98/389) of the cases were the isolates considered “high risk” for pathogenicity. After applying a multivariate regression analysis, advanced donor age was the main associated factor for having culture-positive preservation fluid for high-risk microorganisms. Preemptive antibiotic therapy was given to 19.8% (77/389) of the cases. The incidence rate of preservation fluid–related infection was 1.3% (5 recipients); none of these patients had received preemptive therapy. Solid organ transplant (SOT) recipients with high-risk culture-positive preservation fluid receiving preemptive antibiotic therapy presented both a lower cumulative incidence of infection and a lower rate of acute rejection and graft loss compared with those who did not have high-risk culture-positive preservation fluid. After adjusting for age, sex, type of transplant, and prior graft rejection, preemptive antibiotic therapy remained a significant protective factor for 90-day infection.

Conclusions

The routine culture of preservation fluid may be considered a tool that provides information about the contamination of the transplanted organ. Preemptive therapy for SOT recipients with high-risk culture-positive preservation fluid may be useful to avoid preservation fluid–related infections and improve the outcomes of infection, graft loss, and graft rejection in transplant patients.
A Comparison of Stool Enteropathogen Detection by Semiquantitative PCR in Adults With Acute Travelers’ Diarrhea Before and 3 Weeks After Successful Antibiotic Treatment
Authors: Tisdale Michele D , Tribble David R , Telu Kalyani , Fraser Jamie A , Connor Patrick , Philip Cliff , Odundo Elizabeth , Reyes Faviola , Simons Mark P , Swierczewski Brett , Lizewski Stephen , Liu Jie , Houpt Eric , Riddle Mark S , Lalani Tahaniyat
Published: April 2019

We evaluated stool enteropathogen detection by semiquantitative polymerase chain reaction (PCR) in 108 subjects with travelers’ diarrhea before and 3 weeks after treatment. Stool samples from 21 subjects were positive for the same pathogen species at both visits. We discuss factors that should be considered when interpreting stool PCR data after treatment.
‘A Tortured Nation Gave Birth to a Lunatic’: The Construction of Insanity in the 1912 Terrorist Attack in Croatia
Authors: Fatović-Ferenčić Stella , Kuhar Martin
Published: April 2019

In spring 1912, 25-year-old lawyer Luka Jukić tried to assassinate the Croatian Ban and Royal Commissioner Slavko Cuvaj. This article focuses on several aspects of the trial against Jukić: first, on analysing the impact of Cesare Lombroso’s criminology in Croatia; second, on the testimony by forensic psychiatrist Ivo Žirovčić, who controversially claimed that Jukić was sane; third, on unmasking the techniques and manipulations by the media, the regime and the opposition concerning the assassin’s alleged insanity; and finally, on identifying the ways in which the case influenced further political and revolutionary activities in the country. The discussion concerning Jukić’s accountability deepened the chasm between the supporters and opponents of Cuvaj’s regime, both in the political sphere and within the Croatian medical community.
Gender Role Attitudes and Religious Denomination: Context Matters*
Authors: Healy Amy Erbe
Published: April 2019

Traditional gender role attitudes are often associated with specific religious denominations. However, members of religious denominations are also impacted by other institutions in society. This research uses the European Social Survey to determine how the impact of religious denominations on traditional gender role attitudes varies across welfare regimes. Macro-level analysis examines this relationship with national-level indicators. Religious denomination impacts gender role attitudes, though not uniformly. Public expenditures on social services and working-age cash benefits are negatively related to traditional gender role attitudes, with the strongest impact on attitudes toward men’s right to paid work among Muslims and Eastern Orthodox.
Influence of housing type on the cecal environment of horses
Authors: Wolford Ashley N , Coverdale Josie A , Leatherwood Jessica L , Pinchak William E , Anderson Robin C , Wickersham Tryon A
Published: April 2019

Eight previously cecally cannulated Quarter Horse geldings were utilized in a crossover design with two 28-d periods with a 21-d washout period between to evaluate the influence of housing on the cecal environment and dry matter intake (DMI). Horses were adapted to diet and housing from day 1 to 19, DMI was determined from day 20 to 24, and cecal fluid was collected on day 28. Horses were paired by age and body weight (BW) and randomly assigned to treatment. Treatments consisted of housing horses individually in stalls or group housed in a pen. Regardless of treatment, all horses were individually fed a pelleted concentrate at 1% BW (as fed) offered twice daily 12 h apart. All horses had ad libitum access to coastal bermudagrass hay (Cynodon dactylon). Hay was offered to stalled horses initially at 2% BW (as fed) and then adjusted based on 120% of a previous 3-d average of voluntary intake. A dual marker system was used to estimate forage consumption in all horses, using titanium dioxide (TiO2) as the external marker and acid detergent insoluble ash (ADIA) as the internal marker. TiO2 was offered at 10 g/d for 10 d with fecal samples collected on the final 4 d at 12-h intervals advancing by 3 h each day to account for diurnal variation. Cecal samples were collected on day 28, 4 h after the morning meal and immediately analyzed for pH, total anaerobic and lactic acid bacteria populations, methane and ammonia concentrations, as well as volatile fatty acid (VFA) concentrations. Data were analyzed using the PROC GLM procedure of SAS with the model containing effects for horse, period, and treatment. Cecal pH was affected by housing (P = 0.02) with group-housed horses having lower cecal pH values compared with stalled horses (6.52 vs. 6.69, respectively). There was no influence of housing on populations of total anaerobic or lactic acid bacteria. Furthermore, housing did not influence cecal concentrations of VFA or methane and ammonia concentrations. Estimates of voluntary forage DMI were greater for group-housed horses (P = 0.04) than stalled (8.47 and 5.17 ± 0.89 kg DM/d, respectively). In conclusion, confinement housing did not, with the exception of pH, alter cecal environment of a horse when similar diets were offered but did affect forage consumption.
Microarray screening of differentially expressed genes after up-regulating miR-205 or down-regulating miR-141 in cervical cancer cells
Authors: Fang Xingyu , Yao Tingting
Published: April 2019

Cervical cancer is one of the most common gynecological malignancies. However,studies on the expression and molecular mechanism of miR-205 and miR-141 in CC are insufficient recently. Expression profile microarray with 21329 Oligo DNA were used to detect the expression of mRNAs in miR-205 up-regulated or miR-141 down-regulated HeLa and SiHa cells and mRNAs in normal HeLa and SiHa cells. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed to assess the potential pathways of miR-205 in SiHa cell.Compared with normal HeLa cell, there were 38 differentially expressed genes (DEGs) in miR-205 up-regulated HeLa cell. Nine were up-regulation genes and 29 were down-regulation genes. There were 23 DEGs in miR-141 down-regulated HeLa cell. One was up-regulated and 22 were down-regulated. Compared with normal SiHa cell, there were 128 DEGs in miR-205 up-regulated SiHa cell. One hundred and three were up-regulation genes and 25 were down-regulation genes. There were 80 DEGs in miR-141 down-regulated SiHa cell. Forty two were up-regulation genes and 28 were down-regulation genes. For miR-205 up-regulated SiHa cell, GO outcome showed that “ubiquitin-protein ligase activity”, “MAP kinase phosphatase activity”, were the most enriched terms (P < 0.05). And in KEGG analysis, “Cell cycle” was notably enriched, and Smad4 in this pathway was up-regulated (P < 0.05). Expression profile microarray technology can effectively screen out DEGs in cervical cancer cells after up-regulating miR-205 or down-regulating miR-141. Which may enable us to understand the pathogenesis and lay an important foundation for the prevention and treatment of cervical cancer.
HIV chromatin is a preferred target for drugs that bind in the DNA minor groove
Authors: Little Donald W. , Schafer Samuel J. , Anderson John N.
Published: April 2019

The HIV genome is rich in A but not G or U and deficient in C. This nucleotide bias controls HIV phenotype by determining the highly unusual composition of all majors HIV proteins. Since drugs that bind in the DNA minor groove disrupt nucleosomes on sequences that contain closely spaced oligo-A tracts which are prevalent in HIV DNA because of this bias, it was of interest to determine if these drugs exert this selective inhibitory effect on HIV chromatin. To test this possibility, nucleosomes were reconstituted onto five double-stranded DNA fragments from the HIV-1 pol gene in the presence and in the absence of several minor groove binding drugs (MGBDs). The results demonstrated that the MGBDs inhibited the assembly of nucleosomes onto all of the HIV-1 segments in a manner that was proportional to the A-bias, but had no detectable effect on the formation of nucleosomes on control cloned fragments or genomic DNA from chicken and human. Nucleosomes preassembled onto HIV DNA were also preferentially destabilized by the drugs as evidenced by enhanced nuclease accessibility in physiological ionic strength and by the preferential loss of the histone octamer in hyper-physiological salt solutions. The drugs also selectively disrupted HIV-containing nucleosomes in yeast as revealed by enhanced nuclease accessibility of the in vivo assembled HIV chromatin and reductions in superhelical densities of plasmid chromatin containing HIV sequences. A comparison of these results to the density of A-tracts in the HIV genome indicates that a large fraction of the nucleosomes that make up HIV chromatin should be preferred in vitro targets for the MGBDs. These results show that the MGBDs preferentially disrupt HIV-1 chromatin in vitro and in vivo and raise the possibility that non-toxic derivatives of certain MGBD might serve as a novel class of anti-HIV agents.
A Novel, Versatile Speculum-free Callascope for Clinical Examination and Self-Visualization of the Cervix
Authors: Asiedu Mercy N. , Agudogo Júlia S. , Dotson Mary Elizabeth , Krieger Marlee S. , Schmitt John W. , Huchko Megan , Suneja Gita , Proeschold-Bell Rae Jean , Smith Jennifer S. , Jenson Deborah , Hogan Wesley , Ramanujam Nirmala
Published: April 2019

Background

Invasive cervical cancer is preventable, yet affects 500,000 women worldwide each year, and over half these women die. Barriers to cervical cancer screening include lack of awareness of cervical cancer and the cervix, fear of the speculum, and lack of women-centric technologies. We developed a low-cost (∼$50), cervix-imaging device called the Callascope, which comprises an imaging component, camera and inserter that eliminates the need for a speculum and enables self-insertion. We sought to assess the quality of physicians’ images of the cervix using the Callascope versus the speculum in live patients and study women’s willingness to independently use the Callascope to image their cervix.

Methods

We conducted two main studies: (1) a clinical study in which a physician imaged the cervix of patients using both the speculum and Callascope in a 2×2 crossover design; and (2) home-based self-cervix imaging with the Callascope.

Results

Participants of the clinical study (n=28) and home study (n=12) all indicated greater comfort and an overall preference for the Callascope over the speculum. The clinical study data indicated that the Callascope enabled similar visualization compared to the speculum while significantly improving patient experience. With physician insertion and manipulation, the Callascope enabled cervix visualization for 82% of participants. In the home-study, 83% of participants were able to visualize their cervix with the Callascope on the first try and 100% after multiple attempts.

Conclusion

The Callascope is more comfortable and provides similar visualization to the speculum. The Callascope can be used by medical providers for clinical exams while also enabling home self-screening for cervical cancer and promoting a better understanding of one’s cervix to increase awareness of cervical screening needs. The Callascope may increase cervical cancer screening rates through reducing barriers including cost, discomfort, lack of awareness and stigma.
A broad-host-range CRISPRi toolkit for silencing gene expression in Burkholderia
Authors: Hogan Andrew M. , Rahman A. S. M. Zisanur , Lightly Tasia J. , Cardona Silvia T.
Published: April 2019

Genetic tools are critical to dissecting the mechanisms governing cellular processes, from fundamental physiology to pathogenesis. Members of the genus Burkholderia have potential for biotechnological applications but can also cause disease in humans with a debilitated immune system. The lack of suitable genetic tools to edit Burkholderia GC-rich genomes has hampered the exploration of useful capacities and the understanding of pathogenic features. To address this, we have developed CRISPR interference (CRISPRi) technology for gene silencing in Burkholderia, testing it in B. cenocepacia, B. multivorans and B. thailandensis. Tunable expression was provided by placing a codon-optimized dcas9 from Streptococcus pyogenes under control of a rhamnose-inducible promoter. As a proof of concept, the paaABCDE operon controlling genes necessary for phenylacetic acid degradation was targeted by plasmid-borne sgRNAs, resulting in near complete inhibition of growth on phenylacetic acid as the sole carbon source. This was supported by reductions in paaA mRNA expression. The utility of CRISPRi to probe other functions at the single cell level was demonstrated by knocking down phbC and fliF, which dramatically reduces polyhydroxybutyrate granule accumulation and motility, respectively. As a hallmark of the mini-CTX system is the broad host-range of integration, we putatively identified 67 genera of Proteobacteria that might be amenable to modification with our CRISPRi toolkit. Our CRISPRi tool kit provides a simple and rapid way to silence gene expression to produce an observable phenotype. Linking genes to functions with CRISPRi will facilitate genome editing with the goal of enhancing biotechnological capabilities while reducing Burkholderia’s pathogenic arsenal.

Author contributions

STC conceived the idea and design of the research; AMH designed and cloned the dCas9 constructs; AMH and ASMZ designed the sgRNAs, assessed knockdown phenotypes, processed data, and wrote and edited the manuscript; TJL performed RT-qPCR analysis and edited the manuscript; STC supervised the work and provided financial support.

Graphical Abstract
supFunSim: spatial filtering toolbox for EEG
Authors: Rykaczewski Krzysztof , Nikadon Jan , Duch Włodzisław , Piotrowski Tomasz
Published: April 2019

Recognition and interpretation of brain activity patterns from EEG or MEG signals is one of the most important tasks in cognitive neuroscience, requiring sophisticated methods of signal processing. The supFunSim library is a new Matlab toolbox which generates accurate EEG forward models and implements a collection of spatial filters for EEG source reconstruction, including linearly constrained minimum-variance (LCMV), eigenspace LCMV, nulling (NL), and minimum-variance pseudo-unbiased reduced-rank (MV-PURE) filters in various versions. It also enables source-level directed connectivity analysis using partial directed coherence (PDC) and directed transfer function (DTF) measures. The supFunSim library is based on the well-known Field-Trip toolbox for EEG and MEG analysis and is written using object-oriented programming paradigm. The resulting modularity of the toolbox enables its simple extensibility. This paper gives a complete overview of the toolbox from both developer and end-user perspectives, including description of the installation process and some use cases.
A convolutional neural network for predicting transcriptional regulators of genes in Arabidopsis transcriptome data reveals classification based on positive regulatory interactions
Authors: MacLean Dan
Published: April 2019

Gene Regulatory networks that control gene expression are widely studied yet the interactions that make them up are difficult to predict from high throughput data. Deep Learning methods such as convolutional neural networks can perform surprisingly good classifications on a variety of data types and the matrix-like gene expression profiles would seem to be ideal input data for deep learning approaches. In this short study I compiled training sets of expression data using the Arabidopsis AtGenExpress global stress expression data set and known transcription factor-target interactions from the Arabidopsis PLACE database. I built and optimised convolutional neural networks with a best model providing 95 % accuracy of classification on a held-out validation set. Investigation of the activations within this model revealed that classification was based on positive correlation of expression profiles in short sections. This result shows that a convolutional neural network can be used to make classifications and reveal the basis of those calssifications for gene expression data sets, indicating that a convolutional neural network is a useful and interpretable tool for exploratory classification of biological data. The final model is available for download and as a web application.
Angiosperm speciation speeds up near the poles
Authors: Igea J. , Tanentzap A. J.
Published: April 2019

Recent evidence has questioned whether the Latitudinal Diversity Gradient (LDG), whereby species richness increases towards the Equator, results from higher rates of speciation in the tropics. Allowing for time heterogeneity in speciation rate estimates for over 60,000 angiosperm species, we found that the LDG does not arise from variation in speciation rates because lineages do not speciate faster in the tropics. These results were consistently retrieved using two other methods to test the association between occupancy of tropical habitats and speciation rates. Our speciation rate estimates were robust to the effects of both undescribed species and missing taxa. Overall, our results show that speciation rates follow an opposite pattern to global variation in species richness. Greater ecological opportunity in the temperate zones, stemming from less saturated communities, higher species turnover or greater environmental change, may ultimately explain these results.
Male competition and the evolution of mating and life history traits in experimental populations ofAedes aegypti
Authors: Qureshi Alima , Aldersley Andrew , Hollis Brian , Ponlawat Alongkot , Cator Lauren J.
Published: April 2019

Aedes aegyptiis an important disease vector and a major target of reproductive control efforts. We manipulated the opportunity for sexual selection in populations ofAe. aegyptiby controlling the number of males competing for a single female. Populations exposed to higher levels of male competition rapidly evolved higher male competitive mating success relative to populations evolved in the absence of competition, with an evolutionary response visible after only five generations. We also detected correlated evolution in other important mating and life history traits, such as acoustic signalling, fecundity and body size. Our results indicate that there is ample segregating variation for determinants of male mating competitiveness in wild populations and that increased male mating success trades-off with other important life history traits. The mating conditions imposed on laboratory-reared mosquitoes are likely a significant determinant of male mating success in populations destined for release.
Isotropic expansion of external environment induces tissue elongation and collective cell alignment
Authors: Koyama H. , Fujimori T.
Published: April 2019

Cell movement is crucial for morphogenesis in multicellular organisms. Growing embryos or tissues often expand isotropically, i.e., uniformly, in all dimensions. On the surfaces of these expanding environments, which we call “fields,” cells are subjected to frictional forces and move passively in response. However, the potential roles of isotropically expanding fields in morphogenetic events have not been investigated well. In this study, we mathematically analyzed the effect of isotropically expanding fields using a vertex model, a standard type of multi-cellular model. We found that cells located on fields were elongated along a similar direction each other. Simultaneously, the cell clusters were also elongated, even though field expansion was absolutely isotropic. We then investigated the mechanism underlying these counterintuitive phenomena. In particular, we asked whether elongation was caused by the properties of the field, the cell cluster, or both. Theoretical analyses involving simplification of the model revealed that cell clusters have an intrinsic ability to asymmetrically deform, leading to their elongation. Importantly, this ability is effective only under the non-equilibrium conditions provided by field expansion. This may explain the elongation of the notochord, located on the surface of the growing mouse embryo. We established that passive cell movement induced by isotropically expanding external environments can contribute to both cell and tissue elongation, as well as collective cell alignment, providing key insight into morphogenesis involving multiple adjacent tissues.

Statement of Significance

It is a central question of developmental biology how the symmetric shapes of eggs can develop the asymmetric structures of embryos. Embryos expand through their growth. Simultaneously, elongation of tissues such as the notochord occurs, which is fundamental phenomena of morphogenesis. However, possible relationships between tissue elongation and the expansion of embryos have not been investigated well. Here we mathematically present that, even if the expansion is isotropic, tissues located on the embryos are asymmetrically deformed by the expansion, resulting in elongation. We generalize the effect of expanding environments on tissue elongation through model reduction and uncover the mechanism underlying elongation. This process can be a novel key piece for symmetry breaking of embryos, together with previously established morphogenetic processes.
Telomere dysfunction represses HNF4α leading to impaired hepatocyte development and function
Authors: Niero Evandro L. , Fok Wilson C. , Vessoni Alexandre T. , Brenner Kirsten A. , Batista Luis F.Z.
Published: April 2019

Telomere attrition is a risk factor for end-stage liver disease. Due to a lack of adequate models and intrinsic difficulties in studying telomerase in physiologically relevant cells, the molecular mechanisms responsible for liver disease in patients with telomere syndromes remain elusive. To circumvent that, we used genome editing to generate isogenic human embryonic stem cell lines (hESCs) harboring a clinically relevant mutation in telomerase (DKC1_A353V) and subjected them to an in vitro, stage-specific hepatocyte differentiation protocol, that resembles hepatocyte development in vivo. Our results show that while telomerase is highly expressed in hESCs, it is quickly silenced, due to TERT down-regulation, after endoderm differentiation, and completely absent in in vitro derived hepatocytes, similarly to what is observed in primary hepatocytes. While endoderm derivation is not impacted by telomere shortening, progressive telomere dysfunction impaired hepatic endoderm formation. Consequently, hepatocyte-derivation, as measured by expression of specific markers, as well by albumin expression and secretion, is severely compromised in telomerase mutant cells with short telomeres. Interestingly, this phenotype was not caused by cell death induction or senescence. Rather, telomere shortening induces down regulation of the human hepatocyte nuclear factor 4α (HNF4α), in a p53 dependent manner. Telomerase reactivation, as well as p53 silencing, rescued hepatocyte formation in telomerase mutants. Likewise, conditional expression of HNF4α, even in cells that retained short telomeres, accrued DNA damage, and p53 stabilization, successfully restored hepatocyte formation from hESCS.

Conclusions

Combined, our data shows that telomere dysfunction acts a major regulator of HNF4α during hepatocyte development and function, pointing to a potential novel target for the clinical management of liver disease in telomere-syndrome patients.
Preparation of anti-HER-2 antibody PLGA polymer nano- ultrasound contrast agent In vitro targeting experiment
Authors: Lin Ji , Stevens Molly , Smith John
Published: April 2019

In this report, we demonstrated a novel method to prepare a hollow nano-targeted ultrasound contrast agent carrying anti-HER-2 antibody with high molecular weight polylactic acid-glycolic acid (PLGA) as a film-forming material, and to investigate in vitro targeting and imaging effects. We utilized the camphor as porogen, PLGA nano-ultrasound contrast agent was prepared by modified double emulsion solvent evaporation method. The general characteristics were characterized by scanning electron microscope, transmission electron microscope and laser particle size analyzer. The angiography was performed by carbodiimide method. The anti-HER-2 antibody was used to prepare the PLGA-targeted nano-ultrasound contrast agent with anti-HER-2 antibody. The in-situ imaging ability was evaluated by laser confocal scanning microscopy. Results indicate that the average particle size of PLGA nano-ultrasound contrast agent was (152.00± 58.08) nm. The particles were regular spherical, uniform in size and good in dispersion. In vitro targeting experiments showed that PLGA-targeted contrast agents with anti-HER-2 antibodies were more strongly aggregated on the surface of breast cancer cells. In vitro imaging experiments showed that the PLGA-targeted nano-ultrasound contrast imaging showed a fine and uniform point-like hyperechoic echo, and no significant attenuation of the posterior echo. This study successfully produced a PLGA-targeted nano-ultrasound contrast agent with anti-HER-2 antibody, which can specifically bind to breast cancer cells with high expression of HER-2 receptor in vitro, and the imaging effect in vitro is better.