bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementing the ten steps to successful breastfeeding in multiple hospitals serving low-wealth patients in the US: innovative research design and baseline findings
Authors: Labbok Miriam H , Taylor Emily C , Nickel Nathan C
Published: May 2013

Background

The Ten Steps to Successful Breastfeeding are maternity practices proven to support successful achievement of exclusive breastfeeding. They also are the basis for the WHO/UNICEF Baby-Friendly Hospital Initiative (BFHI). This study explores implementation of these steps in hospitals that serve predominantly low wealth populations.

Methods

A quasi-experimental design with mixed methods for data collection and analysis was included within an intervention project. We compared the impact of a modified Ten Steps implementation approach to a control group. The intervention was carried out in hospitals where: 1) BFHI designation was not necessarily under consideration, and 2) the majority of the patient population was low wealth, i.e., eligible for Medicaid. Hospitals in the research aspect of this project were systematically assigned to one of two groups: Initial Intervention or Initial Control/Later Intervention. This paper includes analyses from the baseline data collection, which consisted of an eSurvey (i.e., Carolina B-KAP), Maternity Practices in Infant Nutrition and Care survey tool (mPINC), the BFHI Self-Appraisal, key informant interviews, breastfeeding data, and formatted feedback discussion.

Results

Comparability was ensured by statistical and non-parametric tests of baseline characteristics of the two groups. Additional findings of interest included: 1) a universal lack of consistent breastfeeding records and statistics for regular monitoring/review, 2) widespread misinterpretation of associated terminology, 3) health care providers’ reported practices not necessarily reflective of their knowledge and attitudes, and 4) specific steps were found to be associated with hospital breastfeeding rates. A comprehensive set of facilitators and obstacles to initiation of the Ten Steps emerged, and hospital-specific practice change challenges were identified.

Discussion

This is one of the first studies to examine introduction of the Ten Steps in multiple hospitals with a control group and in hospitals that were not necessarily interested in BFHI designation, where the population served is predominantly low wealth, and with the use of a mixed methods approach. Limitations including numbers of hospitals and inability to adhere to all elements of the design are discussed.

Conclusions

For improvements in quality of care for breastfeeding dyads, innovative and site-specific intervention modification must be considered.
Novel Gold(I) and Silver(I) Complexes of Phosphorus-1,1,-dithiolates and Molecular Structure of [O,O’-(Bornyl)2PS2]H3NC(CH3)3
Authors: Solak Samet , Aydemir Cemal , Karakus Mehmet , Lönnecke Peter
Published: May 2013

Background

The novel chiral phosphorus-1,1-dithiolates [4-CH3OC6H4P(S)(OR)S]-[H3NC(CH3)3]+ were synthesized by the reaction of [RPS2)]2 (R = 4-MeOC6H4) or P2S5 and the respective alcohol ROH (R = myrtanyl, 2-naphthylethyl, myrtenyl, borneol) in toluene. The reaction of phosphorus-1,1-dithiolates 1–4 and Au(tht)Cl, AuClPPh3 or AgNO3 and PPh3 gave rise to gold(I)- and silver(I)-complexes in THF. All compounds have been characterised by elemental analyses, IR, NMR (1H-, 13C- and 31P-) spectroscopy as well as MS measurements. Optical rotation values confirmed the chirality of the compounds. The Compound 4 has been characterized structurally by X-ray crystallography.

Results

Phosphorus-1,1,-dithiolate compounds were formed as liquids and were treated with suitable amine in order to convert them to their salts 1–4 . They have been successfully characterized spectroscopically (IR, 1H, 13C, 31P NMR) as well as mass spectra. The compound 4 has been also structurally by X-ray crystallography. The compound 4 crystallizes in the orthorhombic space group P2(1)2(1)2(1) with Z = 4. Compounds containing phosphorus and sulfur donor atoms are excellent ligands due to offering many metal complexes especially group 11–12 metals. The synthesis of gold(I) and silver(I) complexes with chiral phosphorus-1,1,-dithiolate and triphenylphosphine have been described and investigated.

Conclusions

In the present work, we report the synthesis, charactreization of the chiral phosphorus-1,1-dithiolate ligands and preparing the gold(I) and silver(I) phosphorus-1,1-dithiolate or S-donor with phosphine complexes. The molecular structure of the Compound 4 was determined by X-ray diffraction. Due to an easy synthesis method of phosphorus-1,1-dithiolate compounds and a good complexion reagent, it is possible the improvement of the collecting metallic gold or silver from the minerals. When the more ionic salt of phosphorus-1,1-dithiolate compounds were prepared in this way, the water can be used as a cheap solvent. As a result, it can be an alternatively method for the collecting metallic gold or silver from the minerals in future.
The development and use of an ELISA-based method to follow the distribution of cellulase monocomponents during the hydrolysis of pretreated corn stover
Authors: Pribowo Amadeus Y , Hu Jinguang , Arantes Valdeir , Saddler Jack N
Published: May 2013

Background

It is widely recognised that fast, effective hydrolysis of pretreated lignocellulosic substrates requires the synergistic action of multiple types of hydrolytic and some non-hydrolytic proteins. However, due to the complexity of the enzyme mixture, the enzymes interaction with and interference from the substrate and a lack of specific methods to follow the distribution of individual enzymes during hydrolysis, most of enzyme-substrate interaction studies have used purified enzymes and pure cellulose model substrates. As the enzymes present in a typical “cellulase mixture” need to work cooperatively to achieve effective hydrolysis, the action of one enzyme is likely to influence the behaviour of others. The action of the enzymes will be further influenced by the nature of the lignocellulosic substrate. Therefore, it would be beneficial if a method could be developed that allowed us to follow some of the individual enzymes present in a cellulase mixture during hydrolysis of more commercially realistic biomass substrates.

Results

A high throughput immunoassay that could quantitatively and specifically follow individual cellulase enzymes during hydrolysis was developed. Using monoclonal and polyclonal antibodies (MAb and PAb, respectively), a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) was developed to specifically quantify cellulase enzymes from Trichoderma reesei: cellobiohydrolase I (Cel7A), cellobiohydrolase II (Cel6A), and endoglucanase I (Cel7B). The interference from substrate materials present in lignocellulosic supernatants could be minimized by dilution.

Conclusion

A double-antibody sandwich ELISA was able to detect and quantify individual enzymes when present in cellulase mixtures. The assay was sensitive over a range of relatively low enzyme concentration (0 – 1 μg/ml), provided the enzymes were first pH adjusted and heat treated to increase their antigenicity. The immunoassay was employed to quantitatively monitor the adsorption of cellulase monocomponents, Cel7A, Cel6A, and Cel7B, that were present in both Celluclast and Accellerase 1000, during the hydrolysis of steam-pretreated corn stover (SPCS). All three enzymes exhibited different individual adsorption profiles. The specific and quantitative adsorption profiles observed with the ELISA method were in agreement with earlier work where more labour intensive enzyme assay techniques were used.
Pseudoaneurysm of the superior lateral genicular artery: case report of a rare complication after total knee arthroplasty
Authors: Saini Pramod , Meena Sanjay , Malhotra Rajesh , Gamanagatti Shivanand , Kumar Vijay , Jain Vaibhav
Published: May 2013

Background

Pseudoaneurysm of superior lateral genicular artery following total knee arthroplasty is a rare complication and has been reported following lateral release performed for eversion of patella in a knee with tight lateral structures.

Case presentation

This report describes a case of pseudo aneurysm of superior lateral geniculate artery that developed after primary Total knee arthroplasty for a stiff knee in a 68 year old patient. Patient presented with pain and rapidly increasing swelling in early post operative period. Diagnosis was made on duplex ultrasound and confirmed by angiography. Angiographic coil embolisation of the pseudoaneurysm was performed. Since no lateral release was performed in this case, the probable mechanism was shear injury to the vessel.

Conclusion

Pseudoaneurysm of superior lateral genicular artery can occur in absence of lateral release by shear injury to an atherosclerotic vessel. Angiographic coil embolisation appears to be the best method for treating such post arthroplasty pseudoaneurysm because of less chance of infection, non interference with rehabilitation and diagnosis and treatment during same procedure.
Effect of Aedes aegypti exposure to spatial repellent chemicals on BG-Sentinel™ trap catches
Authors: Salazar Ferdinand V , Achee Nicole L , Grieco John P , Prabaripai Atchariya , Ojo Tolulope A , Eisen Lars , Dureza Christine , Polsomboon Suppaluck , Chareonviriyaphap Theeraphap
Published: May 2013

Background

An integrated approach to reduce densities of adult Aedes aegypti inside homes is currently being evaluated under experimentally controlled field conditions. The strategy combines a spatial repellent (SR) treatment (applied indoors) with the Biogents Sentinel™ (BGS) mosquito trap positioned in the outdoor environment. In essence, when combined, the goal is to create a push-pull mechanism that will reduce the probability of human-vector contact. The current study measured BGS recapture rates of Ae. aegypti test cohorts that were exposed to either SR or control (chemical-free) treatments within experimental huts. The objective was to define what, if any, negative impact SR may have on BGS trap efficacy (i.e., reduced BGS collection).

Methods

Aedes aegypti females were exposed to SR compounds within experimental huts in the form of either treated fabric (DDT and transfluthrin) or mosquito coil (metofluthrin). Test cohorts were released within individual screen house cubicles, each containing 4 BGS traps, following SR exposure according to treatment. Two separate test cohorts were evaluated: (i) immediate release (IR) exposed from 06:00–12:00 hours and released at 12:00 hours and (ii) delayed release (DR) exposed from12:00–18:00 hours and released at 05:30 hours the following day. BGS recapture was monitored at 09:30, 13:30 and 15:30 hours and the cumulative recapture by time point quantified.

Results

Exposure of Ae. aegypti females to either DDT or metofluthrin did not significantly impact BGS capture as compared to cohorts of non-exposed females. This was true for both IR and DR exposure populations. IR cohorts exposed to transfluthrin resulted in significantly lower BGS recapture compared to matched controls but this effect was primarily due to high mosquito mortality during transfluthrin trials.

Conclusion

Our data indicate no more than minor and short-lived impacts (i.e., reduced attraction) on BGS trap catches following exposure to the pyrethroid compounds transfluthrin and metofluthrin and no change in recapture densities using DDT as compared to matched controls. These findings suggest a combined SR and BGS approach to vector control could function as a push-pull strategy to reduce Ae. aegypti adults in and around homes.
Embodied Politics: Antebellum Vegetarianism and the Dietary Economy of Walden
Authors: Neely Michelle C.
Published: May 2013

Near the beginning of Walden, Henry David Thoreau tells his readers that his “experiment in living” is dedicated to learning “what are the gross necessaries of life... the grossest groceries,” a choice of metaphor that might remind us just how much of his personal and political reform project in Walden hinges on diet and Thoreau's attitude toward literal “groceries.” Thoreau's interest in dietary practices has generally been read as apolitical or even antipolitical, primarily because his dietary and consumptive practices have never been adequately situated amid contemporary antebellum debates about diet and food commodity consumption. A turn to Sylvester Graham's vegetarian movement, however, shows that far from being divorced from civic concerns, the vegetarian dietary theory driving Thoreau's practices at Walden Pond plays a complicated role in the political design of Walden. Uniting private practices with public reform, Thoreau draws on Graham's theory of a universal physiological constitution that all human beings, and perhaps even animals, could be imagined to possess, in order to denominate the human body as a significant site of political reform. Ultimately, antebellum vegetarians such as Graham and Thoreau restricted appetite for animal foods and commodities in order to reform, reshape, and remake what they viewed as a flawed democratic body, reimagining the limits of citizenship and civic participation in the process.
Unsanitized Domestic Allegories: Biomedical Politics, Racial Uplift, and the African American Woman's Risk Narrative
Authors: Knadler Stephen
Published: May 2013

“Unsanitized Domestic Allegories” begins the work of recovering the complex history linking Progressive-Era biomedicalization, gender expectations, and ideologies of racial uplift within African American culture. Through a close reading of early-twentieth-century African American health care activists, including C. V. Roman, founding member of the National Medical Association (1895) and the first editor of the Journal of the National Medical Association, E. Elliott Rawlins, health columnist for the Amsterdam News, and Mary Fitzbutler Waring, chair of the Committee for Health and Hygiene of the National Association for Colored Women, Knadler's essay argues that race leaders recruited a language of health and hygiene to shape, manage, and regulate the class divisions and cultural disorientations of urban migration. But this community epidemiology was also connected to a particular biomediated image that functioned as part of a politics of risk and affect to preempt women's freedom: the (un)sanitized woman who was said to endanger the health of her family and the community at a time when many African American neighborhoods were experiencing epidemics of diseases as a result of health-care disparities and environmental racism. Knadler then turns to a close reading of Nella Larsen's Quicksand (1928) to show how its unruly, unsanitized domestic allegory exposes and destabilizes this interworking of medical language, affect, and gendered risk within racial uplift. Quicksand testifies to the complex meaning of agency in a world in which political, economic, and moral crises have been recast as the medical condition of specific “risky” bodies and doubts over their competence at maintaining sanitary self-care.
Realism's Ghosts: Science and Spectacle inTom Jones
Authors: Drury Joseph
Published: May 2013

The performative dimension of Fielding's fiction has often frustrated the attempts of critics to read the machinery of his plot through the lens of rationalist Enlightenment philosophy. Rather than a deity or benevolent magistrate, Fielding's narrator has seemed more like a trickster or charlatan manipulating a narrative full of spectacular coincidences and implausibilities. Historians of science, however, have shown that performances with spectacular machines played a key role in establishing the epistemological authority of empirical science in the eighteenth century. Like Fielding, moreover, eighteenth-century natural philosophers were accused of being charlatans staging magic shows. To distinguish themselves from their rivals, therefore, philosophers had to perform “boundary-work” in which they contrasted the enlightened knowledge produced by their performances with the vulgar superstition they claimed was perpetuated by magic shows. Fielding performs the same boundary-work in Tom Jones, carefully contrasting the enlightened “poetic Faith” solicited by the rationalized clockwork of his plot with the superstition incited by the baroque machinery of spectacular narratives that he represents as barbarous, foreign, and antiquated. But he also follows other Augustan authors in acknowledging that the entertainments popular in the culture of spectacle had distinctly modern, domestic origins and that the residual “superstition” they cultivated was really the commodity fetishism integral to a new capitalist system of production. Fielding's goal in Tom Jones was thus not to eliminate manipulative spectacle from modern narrative but to harness it by directing it toward the higher purpose of producing philosophical knowledge.
Humane-Itarian Interventions
Authors: Rangan Pooja
Published: May 2013

This essay critically examines humanitarian efforts to rehabilitate captive and working animals as producers of art—a practice recently and controversially popularized by viral videos of former draft elephants in Thai tourist camps painting self-portraits for sale. Positioning these initiatives as “humane-itarian media interventions” that merge the rhetorical immediacy of humanitarian witnessing with the disciplinary logic of humane reform, the author argues that they recapture animals within anthropocentric regulatory coordinates of agency. To examine how contemporary “posthumanist” inquiries into the animal condition depart from and partake of interventionist logics, the essay contrasts humane-itarian artworks with those of contemporary artists Sam Easterson, Lisa Jevbratt, Beatriz da Costa, and Simon Starling, who surrender their media (ranging from video cameras, iPhones, and GPS devices, to steel) within animal environments to obtain indexical inscriptions from animal collaborators. This essay argues that the radically passive orientation of these collaborative artworks puts into practice Roger Caillois's psychasthenic theory of animal mimicry, which employs minoritarian modes of agency to defamiliarize our habituated relations with our medial environment. By confronting mediation as an unresolved but nonetheless generative ethical problem, these artists offer lines of flight from interventionist thinking even as they partake of a resolutely humanist mode of mediation.
Serbia “Enters” Europe: International Mobility and the Redrawing of State Boundaries
Authors: Sasikumar Karthika
Published: May 2013

In 2009, citizens of Serbia were finally allowed to make short trips to Schengen zone countries without visas. This represented a victory for the regime in Belgrade. A whole generation of Serbians had been held back from European travel by the visa requirement that was introduced as Yugoslavia disintegrated. However, this victory came at a price. Schengen countries worried that the lifting of the visa barrier would trigger a flood of illegal workers and asylum seekers from Kosovo. The Serbian government, which considers Kosovo to be an autonomous province, had to come up with an expedient solution to reassure wealthier European countries that allowing Serbians to “enter” would not open the gates to a large number of problematic visitors. Eventually, Belgrade agreed to restrict the privilege of visa-free travel for residents of Kosovo, formally differentiating Kosovar citizens from “normal” citizens. The imperatives of international mobility have forced a country, in a sense, to redraw its boundaries and to acknowledge a different status for a section of its population from a province that it continues to claim. This essay unpacks the puzzle of why supporters of the “integral Kosovo” position in Serbia resigned themselves to the compromise. The central argument is that states seek to secure mobility not only for economic reasons but also to mark themselves as normal, respectable members of the international community. Serbia’s visa waiver decision provides a lens with which to view issues of mobility and national identity in one of the most complex and divided regions of the world.
Albania and the Middle East
Authors: Bishku Michael B.
Published: May 2013

This essay reviews and analyzes Albania’s connections with the Middle East since the era of Enver Hoxha’s rule, when ideology was a strong factor in international relations. Since the end of the Cold War, Albania has been most interested in developing political, economic, and cultural ties, especially with Turkey, Israel, and the Arab states of the Persian Gulf region. Through its modern history, Albania has been a good example of a politically and economically weak state exercising a fairly consistent asymmetric foreign policy based on the support of great powers and their allies.
Performance Collectives in 1960s Japan: With a Focus on the “Ritual School”
Authors: KuroDalaiJee
Published: May 2013

This essay focuses on a set of artists' collectives I call “ritual school.” The ritualist collectives distinguished themselves among numerous performance collectives that emerged throughout Japan from the late 1950s to the late 1960s by their antimodern styles, distinct mode of collectivism that transcended the narrow confines of “art” (bijutsu), and specific social strategies. Among the ritualists, Zero Jigen, which stood out in terms of their numerous performances and contingent styles, and other collectives such as Kokuin and factions of The Play, with other individuals, formed Expo '70 Destruction Joint-Struggle Group (EDG) in 1969. The EDG presented an alternative manner of art collectives in its open “joint-struggle” with other collectives and individuals, as well as in its collaboration with other cultural practitioners and political activists who shared the anarchic, antiinstitutional, and underground cultures in Tokyo and Kyoto in the late 1960s.
Authority, Autonomy, and the Early Taishō “Avant-Garde”
Authors: Volk Alicia
Published: May 2013

This essay addresses the problematic notion of the “avant-garde” in the context of Japanese modern art. It looks at the formation in 1907 of the national salon, the Bunten, to elucidate the relational dynamics of art organizations in early twentieth-century Japan, especially during the Taisho period (1912 – 27) when the Fusain Society (Fyûzankai) and the Nika Society (Nikakai) came into being as alternatives to the Bunten. The essay elucidates one of the fundamental paradoxes of Taisho-period art — the simultaneous proliferation of art organizations and artistic individualism — and the dialectic between authority and autonomy that prevailed in art under the conditions of Japanese modernity.
Vinculin tension distributions of individual stress fibers within cell-matrix adhesions
Authors: Chang Ching-Wei , Kumar Sanjay
Published: May 2013

Actomyosin stress fibers (SFs) enable cells to exert traction on planar extracellular matrices (ECMs) by tensing focal adhesions (FAs) at the cell-ECM interface. While it is widely appreciated that the spatial and temporal distribution of these tensile forces play key roles in polarity, motility, fate choice, and other defining cell behaviors, virtually nothing is known about how an individual SF quantitatively contributes to tensile loads borne by specific molecules within associated FAs. We address this key open question by using femtosecond laser ablation to sever single SFs in cells while tracking tension across vinculin using a molecular optical sensor. We show that disruption of a single SF reduces tension across vinculin in FAs located throughout the cell, with enriched vinculin tension reduction in FAs oriented parallel to the targeted SF. Remarkably, however, some subpopulations of FAs exhibit enhanced vinculin tension upon SF irradiation and undergo dramatic, unexpected transitions between tension-enhanced and tension-reduced states. These changes depend strongly on the location of the severed SF, consistent with our earlier finding that different SF pools are regulated by distinct myosin activators. We critically discuss the extent to which these measurements can be interpreted in terms of whole-FA tension and traction and propose a model that relates SF tension to adhesive loads and cell shape stability. These studies represent the most direct and high-resolution intracellular measurements of SF contributions to tension on specific FA proteins to date and offer a new paradigm for investigating regulation of adhesive complexes by cytoskeletal force.
Plakoglobin interacts with the transcription factor p53 and regulates the expression of 14-3-3σ
Authors: Aktary Zackie , Kulak Stephen , Mackey John , Jahroudi Nadia , Pasdar Manijeh
Published: May 2013

Plakoglobin (γ-catenin), a constituent of the adherens junction and desmosomes, has signaling capabilities typically associated with tumor/metastasis suppression through mechanisms that remain undefined. To determine the role of plakoglobin during tumorigenesis and metastasis, we expressed plakoglobin in human tongue squamous cell carcinoma (SCC9) cells and compared the mRNA profiles of parental SCC9 cells and their plakoglobin-expressing transfectants (SCC9-PG). We detected several p53-target genes whose levels were altered upon plakoglobin expression. In this study, we identified the p53 regulated tumor suppressor 14-3-3σ as a direct plakoglobin-p53 target gene. Coimmunoprecipitation experiments revealed that plakoglobin and p53 interact while chromatin immunoprecipitation and electrophoretic mobility shift assays revealed that plakoglobin and p53 associate with the 14-3-3σ promoter. Furthermore, luciferase reporter assays showed that p53 transcriptional activity is increased in the presence of plakoglobin. Finally, knockdown of plakoglobin in MCF-7 cells followed by luciferase assays confirmed that p53 transcriptional activity is enhanced in the presence of plakoglobin. Our data suggest that plakoglobin regulates gene expression in conjunction with p53 and that plakoglobin may regulate p53 transcriptional activity, which may account, in part, for the tumor/metastasis suppressor activity of plakoglobin.
PfSec13 is an unusual chromatin associated nucleoporin of Plasmodium falciparum, which is essential for parasite proliferation in human erythrocytes
Authors: Dahan-Pasternak Noa , Nasereddin Abed , Kolevzon Netanel , Pe'er Michael , Wong Wilson , Shinder Vera , Turnbull Lynne , Whitchurch Cynthia B. , Elbaum Michael , Gilberger Tim W. , Yavin Eylon , Baum Jake , Dzikowski Ron
Published: May 2013

In Plasmodium falciparum, the deadliest form of human malaria, the nuclear periphery has drawn much attention due to its role as a sub-nuclear compartment involved in virulence gene expression. Recent data have implicated components of the nuclear envelope in regulating gene expression in several eukaryotes. Special attention has been given to nucleoporins that compose the nuclear pore complex. However, very little is known about components of the nuclear envelope in Plasmodium parasites. Here we characterize PfSec13, an unusual nucleoporin of P. falciparum, which shows unique structural similarities suggesting it is a fusion between Sec13 and Nup145C of yeast. Using super resolution fluorescence microscopy (3D-SIM) and in vivo imaging we show that the dynamic localization of PfSec13 during parasites' intra-erythrocytic development corresponds with that of the NPCs and that these dynamics are associated with microtubules rather than with F-actin. In addition, PfSec13 does not co-localize with the heterochomatin markers HP1 and H3K9me3, suggesting euchromatic location of the NPCs. The proteins associated with PfSec13 indicate that this unusual Nup is involved in several cellular processes. Indeed, ultrastructural and ChIP analyses revealed that in addition to the NPCs, PfSec13 is found in the nucleoplasm where it is associated with chromatin. Finally, we used Peptide Nucleic Acids (PNA) to down-regulate PfSec13 and show that is essential for parasite proliferation in human erythrocytes.
A gap junction docking mechanism revealed by functional rescue of a human disease-linked connexin mutant
Authors: Gong Xiang-Qun , Nakagawa So , Tsukihara Tomitake , Bai Donglin
Published: May 2013

Gap junctions (GJ) are unique intercellular channels formed by proper docking of two hemichannels from adjacent cells. Each hemichannel is a hexamer of connexins (Cxs) - the GJ subunits encoded by 21 homologous genes in the human genome. The docking of two hemichannels to form a functional GJ channel is only possible between compatible Cxs, but the underlying molecular mechanism is unclear. Based on Cx26 GJ crystal structure we developed homology models for homotypic and heterotypic channels from Cx32 and/or Cx26; these models predict 6 hydrogen bonds (HBs) at the docking-interface of each pair of the second extracellular domains (E2). Cx32 mutation N175H and a human disease-linked mutant N175D were predicted to lose majority of the HBs at the E2 docking-interface; experimentally both mutations failed to form morphological and functional GJs. To restore the lost HBs, two complementary Cx26 mutants – K168V and K168A were designed to pair with the Cx32 mutants. When docked with Cx26K168V or K168A, Cx32N175H mutant was successfully rescued morphologically and functionally in forming GJ channels; but not Cx32 mutant N175Y. By testing more Cx32/Cx26 mutant combinations, it is revealed that a minimum of 4 HBs at each E2 docking-interface are required for proper docking and functional channel formation between Cx26 and Cx32 hemichannels. Interestingly the disease-linked Cx32N175D could be rescued by Cx26D179N, which restored 5 HBs at the E2 docking interface. Our findings provide not only a GJ docking mechanism for Cx26 and Cx32 hemichannels, but also a potential therapeutic strategy for GJ channelopathies.
TheDrosophilaTRP and TRPL are assembled as homomultimeric channels in vivo
Authors: Katz Ben , Oberacker Tina , Richter David , Tzadok Hanan , Peters Maximilian , Minke Baruch , Huber Armin
Published: May 2013

Family members of the cationic TRP channels serve as sensors and transducers of environmental stimuli. The ability of different TRP channel isoforms of specific subfamilies to form heteromultimers and the structural requirements for channel assembly are still unresolved. Although heteromultimerization of different mammalian TRP channels within single subfamilies has been described, even within the TRPC subfamily, not all members co-assemble with each other. In Drosophila photoreceptors two TRPC channels, TRP and TRPL are expressed together in photoreceptors where they generate the light induced current. The formation of functional TRP-TRPL heteromultimers in cell culture and in vitro was reported. However, functional in vivo assays have shown that each channel functions independently of the other. Therefore, the issue whether TRP and TRPL form heteromultimers in vivo is still unclear. In the present study we investigated the ability of TRP and TRPL to form heteromultimers and the structural requirements for channel assembly, by studying assembly of GFP-tagged TRP and TRPL channels and chimeric TRP and TRPL channels, in vivo. Interaction studies of tagged and native channels as well as native and chimeric TRP-TRPL channels using co-immunoprecipitation, immunocytochemistry and electrophysiology, critically tested the ability of TRP and TRPL to interact. We found that TRP and TRPL assemble exclusively as homomultimeric channels in their native environment. The above analyses revealed that the transmembrane regions of TRP and TRPL did not determine assemble specificity of these channels. However, the C-terminal regions of both TRP and TRPL predominantly specify the assembly of homomeric TRP and TRPL channels.
Depletion of RAD17 sensitizes pancreatic cancer cells to gemcitabine
Authors: Fredebohm Johannes , Wolf Jonas , Hoheisel Jörg D. , Boettcher Michael
Published: May 2013

Chemotherapy of advanced pancreatic cancer has mainly been gemcitabine-based for the past fifteen years, with only limited effect. Recently, combination therapy that also targets checkpoint kinase 1 (CHK1) has become an attractive option. The central role of CHK1 in many DNA damage response pathways, however, may result in undesired cytotoxicity in normal cells causing side effects. We were searching for other target molecules of similar function that may be more specific and thus better suited for combination therapy. To this end a negative selection RNAi screen was performed in cell lines with small hairpin RNA molecules targeting over 10,000 genes. Genes that were found to be synthetically lethal with gemcitabine and whose proteins are acting upstream of CHK1 were characterised in more detail. In particular, the inhibition of RAD17 potentiated gemcitabine cytotoxicity in the pancreatic cancer cell lines BxPC-3, MiaPaca-2 and the primary cell line JoPaca-1 that closely resembles primary tumour tissue. Further analysis showed that the synergistic effect of RAD17 knockdown and gemcitabine leads to forced mitotic entry of cells arrested in S-phase by gemcitabine treatment, resulting in asymmetric DNA distribution during anaphase followed by DNA fragmentation and finally cell death by mitotic catastrophe. Our data suggest RAD17 as a novel target for gemcitabine combination therapy supplementing or complementing inhibition of checkpoint kinase 1. As opposed to CHK1, RAD17 knockdown by itself does not lead to abnormal DNA segregation, suggesting a more specific action.
A ligand-specific kinetic switch regulates glucocorticoid receptor trafficking and function
Authors: Trebble Peter J. , Woolven James M. , Saunders Ken A. , Simpson Karen D. , Farrow Stuart N. , Matthews Laura C. , Ray David W.
Published: May 2013

The ubiquitously expressed glucocorticoid receptor (GR) is a major drug target for inflammatory disease, but issues of specificity, and target tissue sensitivity remain. We now identify high potency, non-steroidal GR ligands, GSK47867A and GSK47869A, which induce a novel conformation of the GR ligand binding domain (LBD) and augment the efficacy of cellular action. Despite their high potency GSK47867A and GSK47869A both induce surprisingly slow GR nuclear translocation, followed by prolonged nuclear GR retention, and transcriptional activity following washout. We reveal that GSK47867A and GSK47869A specifically alter the GR LBD structure at the HSP90 binding site. The alteration in HSP90 binding site was accompanied by resistance to HSP90 antagonism, with persisting transactivation seen after geldanamycin treatment. Taken together, our studies reveal a novel mechanism governing GR intracellular trafficking regulated by ligand binding, which relies on a specific surface charge patch within the LBD. This conformational change permits extended GR action, likely due to altered GR-HSP90 interaction. This chemical series may offer anti-inflammatory drugs with prolonged duration of action due to altered pharmacodynamics rather than altered pharmacokinetics.
Metabolic energy sensors (AMPK and SIRT1), protein carbonylation, and cardiac failure as biomarkers of thermal stress in an intertidal limpet: linking energetic allocation with environmental temperature during aerial emersion
Authors: Han Guo-dong , Zhang Shu , Marshall David J. , Ke Cai-huan , Dong Yun-wei
Published: May 2013

The effects of heat stress on organisms are manifested at the levels of organ function, metabolic activity, protein stability and gene expression. Here, we examined effects of high temperature on the intertidal limpet Cellana toreuma to determine how the temperatures at which organ failure (cardiac function), irreversible protein damage (carbonylation), and expression of genes encoding proteins involved in molecular chaperoning (hsp70 and hsp90) and metabolic regulation (ampk and sirt1) compare with field temperatures, which commonly exceed 30°C and can reach 46°C. Heart failure, indexed by the Arrhenius break temperature (ABT) was 34.3°C. Protein carbonylation rose significantly at 38°C. Genes for heat shock proteins HSP70 (hsp70) and HSP90 (hsp90), for two subunits of AMP-activated protein kinase (AMPK) (ampkα and ampkβ), and for histone/protein deacetylase SIRT1 (sirt1) all showed increased expression at 30°C. Temperatures of maximal expression differed among genes, as did temperatures at which up-regulation ceased. Expression patterns for ampk and sirt1 indicate that heat stress influenced cellular energy homeostasis; above ~30°C, up-regulation of ATP-generating pathways is suggested by elevated expression of genes for ampk; an altered balance between reliance on carbohydrate and lipid fuels is indicated by changes in expression of sirt1. These results show that C. toreuma commonly experiences temperatures that induce expression of genes associated with the stress response (hsp70 and hsp90) and regulation of energy metabolism (ampk and sirt1). At high temperatures, there is likely to be a shift away from anabolic processes like growth to catabolic processes, to provide energy for coping with stress-induced damage, notably to proteins.
Limited effects of exogenous glucose during severe hypoxia and a lack of hypoxia-stimulated glucose uptake in isolated rainbow trout cardiac muscle
Authors: Becker Tracy A. , DellaValle Brian , Gesser Hans , Rodnick Kenneth J.
Published: May 2013

We examined whether exogenous glucose affects contractile performance of electrically-paced ventricle strips from rainbow trout under conditions known to alter cardiomyocyte performance, ion regulation, and energy demands. Physiological levels of D-glucose did not influence twitch force development for aerobic preparations 1) paced at 0.5 or 1.1 Hz, 2) at 15 or 23°C, 3) receiving adrenergic stimulation, or 4) during reoxygenation with or without adrenaline after severe hypoxia. Contractile responses to ryanodine, an inhibitor of Ca2+ release from the sarcoplasmic reticulum, were also not affected by exogenous glucose. However, glucose did attenuate the fall in twitch force during severe hypoxia. Glucose uptake was assayed in non-contracting ventricle strips using 2-[3H] deoxy-D-glucose (2-DG) under aerobic and hypoxic conditions, different incubation temperatures, and inhibitors. Based upon a lack of saturation of 2-DG uptake and incomplete inhibition of uptake by cytochalasin B and D-glucose, 2-DG uptake was mediated by a combination of facilitated transport and simple diffusion. Hypoxia stimulated lactate efflux 6-7-fold with glucose present, but did not increase 2-DG uptake or reduce lactate efflux in the presence of cytochalasin B. Increasing temperature (14 to 24°C) also did not increase 2-DG uptake, but decreasing temperature (14 to 4°C) reduced 2-DG uptake by 45%. In conclusion, exogenous glucose improves mechanical performance under hypoxia but not under any of the aerobic conditions applied. The extracellular concentration of glucose and cold temperature appear to determine and limit cardiomyocyte glucose uptake, respectively, and together may help define a metabolic strategy that relies predominantly on intracellular energy stores.
Chemical structure of odorants and perceptual similarity in ants
Authors: Bos Nick , d'Ettorre Patrizia , Guerrieri Fernando J.
Published: May 2013

Animals are often immersed in a chemical world consisting of mixtures of many compounds rather than of single substances, and they constantly face the challenge of extracting relevant information out of the chemical landscape. To this purpose, the ability to discriminate among different stimuli with different valence is essential, but it is also important to be able to generalise, i.e. to treat different but similar stimuli as equivalent, as natural variation does not necessarily affect stimulus valence. Animals can thus extract regularities in their environment and make predictions, for instance about distribution of food resources. We studied perceptual similarity of different odours by conditioning individual carpenter ants to one odour, and subsequently testing their response to another, structurally different odour. We found that asymmetry in generalisation, where ants generalise from odour ’A’ to ’B’, but not from ’B’ to ’A’, is dependent on both chain length and functional group. By conditioning ants to a binary mixture, and testing their reaction to the individual components of the mixture, we show that overshadowing, where parts of a mixture are learned better than others, is rare. Additionally, generalisation is not only dependent on the structural similarity of odorants, but their functional value might play a crucial role. Our results help understanding how ants make sense of the complex chemical world around them, and provide a basis to investigate the neural mechanisms behind perceptual similarity.
Nitric oxide and coral bleaching: is peroxynitrite generation required for symbiosis collapse?
Authors: Hawkins Thomas D. , Davy Simon K.
Published: May 2013

The temperature-induced collapse ("bleaching") of the coral-dinoflagellate symbiosis is hypothesised to result from symbiont oxidative stress and a subsequent host innate immune-like response. This includes the production of nitric oxide (NO), which is involved in numerous microbial symbioses. Much of NO's cytotoxicity has been attributed to its conversion, in the presence of superoxide (O2-), to highly reactive peroxynitrite (ONOO-). However, ONOO- generation has yet to be observed in either a lower invertebrate or intracellular mutualism. Using confocal laser scanning microscopy with the fluorescent ONOO- indicator aminophenyl fluorescein (APF), we observed strong evidence that ONOO- is generated in symbiotic Aiptasia pulchella under conditions known to induce thermal bleaching. However, a role for ONOO- in bleaching remains unclear as treatment with a peroxynitrite scavenger had no significant effect on thermal bleaching. Therefore, while ONOO- may have a potential for cytotoxicity, in vivo levels of the compound may be insufficient to affect bleaching.
Rough eyes of the Northeast-Asian Wood White Leptidea amurensis
Authors: Uchiyama Hironobu , Awata Hiroko , Kinoshita Michiyo , Arikawa Kentaro
Published: May 2013

The Northeast-Asian Wood White Leptidea amurensis (Lepidoptera, Pieridae) belongs to Dismorphiinae, a subfamily of the family Pieridae. We here studied the structure of the compound eye in this species through a combination of anatomy, molecular biology and intracellular electrophysiology, with a particular focus on the evolution of butterfly eyes. We found that their eyes consist of three types of ommatidia, with a basic set of one short, one middle and one long wavelength-absorbing visual pigment. The spectral sensitivities of the photoreceptors are rather simple, and peak in the ultraviolet, blue and green wavelength regions. The ommatidia have neither perirhabdomal nor fluorescent pigments, which modulate photoreceptor spectral sensitivities in a number of other butterfly species. These features are primitive, but the eyes of Leptidea exhibit another unique feature: the rough appearance of the ventral two-thirds of the eye. The roughness is due to the irregular distribution of facets of two distinct sizes. As this phenomenon exists only in males, it may represent a newly evolved sex-related feature.
The San Francisco Declaration on Research Assessment
Authors: Hoppeler Hans
Published: May 2013

On 16 December 2012, a group of editors and publishers of scholarly journals gathered together at the Annual Meeting of The American Society for Cell Biology in San Francisco, CA, USA to discuss current issues related to how the quality of research output is evaluated and how the primary scientific literature is cited. The outcome of the meeting and further discussions is a set of recommendations that is referred to as the San Francisco Declaration on Research Assessment, published in May 2013. The Journal of Experimental Biology (JEB) fully supports this initiative. In concordance with the recommendations of the Declaration, JEB provides impact factor alongside a variety of other journal-based metrics, requests an author contribution statement for all Research Articles, places no restrictions on the reuse of reference lists, and has no limitations on the number of references in Research Articles.
Redox Switching of Conjugation Length Using 9,9,10,10-Tetraaryl-9,10-dihydrophenanthrene as an ON/OFF Unit: Preparation, X-ray Structure, and Redox Properties of Perfluorobiphenyl Derivative and Its SNAr Reactions to π-Extended Analogues
Authors: Suzuki Takanori , Tamaoki Hitomi , Katoono Ryo , Fujiwara Kenshu , Ichikawa Junji , Fukushima Takanori
Published: May 2013

Octafluorobiphenyl-2,2′-diylbis(diarylmethylium) dye 2a2+ prepared from 1,2-dibromotetrafluorobenzene is interconvertible with colorless dihydrophenanthrene donor 1a. By the SNAr reactions of 1a with acetylides, π-extended analogues 1b and 1c were obtained. Their electrochromic behavior is accompanied by a drastic absorption change not only in the visible but also UV region, because the torsion angle of the biaryl unit is modified upon redox reactions.
A Nation of Gamblers: Real Estate Speculation and American History
Authors: Glaeser Edward L
Published: May 2013

The great housing convulsion that buffeted America between 2000 and 2010 has historical precedents, from the frontier land boom of the 1790s to the skyscraper craze of the 1920s. But this time was different. There was far less real uncertainty about fundamental economic and geographic trends, making the convulsion even more puzzling. During historic and recent booms, sensible models could justify high prices on the basis of seemingly reasonable projections about stable or growing prices. The recurring error appears to be a failure to anticipate the impact that elastic supply will eventually have on prices, whether for cotton in Alabama in 1820 or land in Las Vegas in 2006. Buyers don't appear to be irrational but rather cognitively limited investors who work with simple heuristic models, instead of a comprehensive general equilibrium framework. Low interest rates rarely seem to drive price growth; underpriced default options are a more common contributor to high prices. The primary cost of booms has not typically been overbuilding, but rather the financial chaos that accompanies housing downturns.
Growth Forecast Errors and Fiscal Multipliers
Authors: Blanchard Olivier J , Leigh Daniel
Published: May 2013

This paper investigates the relation between growth forecast errors and planned fiscal consolidation during the crisis. We find that, in advanced economies, stronger planned fiscal consolidation has been associated with lower growth than expected. The relation is particularly strong, both statistically and economically, early in the crisis. A natural interpretation is that fiscal multipliers were substantially higher than implicitly assumed by forecasters. The weaker relation in more recent years may in part reflect learning by forecasters and in part smaller multipliers than in the early years of the crisis.
Bailouts and the Optimal Taxation of Bonus Pay
Authors: Besley Timothy , Ghatak Maitreesh
Published: May 2013

This paper argues that the possibility of bailouts to financial intermediaries distorts the supply price of capital and creates an argument for taxing financial bonuses separately from other sources of income. We develop a model of financial contracting where intermediaries compete for workers whose actions affect productivity and risk-taking in the financial sector. This derives the second-best optimum and market equilibrium. The optimal taxes that we propose increase both equity and efficiency compared to the pure market outcome.
Deconstructing Income and Income Inequality Measures: A Crosswalk from Market Income to Comprehensive Income
Authors: Armour Philip , Burkhauser Richard V , Larrimore Jeff
Published: May 2013

Recent research on levels and trends in the United States in income inequality vary substantially in how they measure income. We show the sensitivity of alternative income measures in capturing income trends using a unified data set. Focusing solely on market income or including realized taxable capital gains based on IRS tax return data in more comprehensive household income measures will dramatically increase inequality growth compared to capital gains measures more in keeping with Haig-Simons principles. Using a measure of yearly accrued capital gains dramatically reduces observed growth in income inequality across the distribution, but also equalizes income growth since 1989.