bluuebunny/crossref_metadata_2025_split huggingface dataset:
The response threshold of SalmonellaPilZ domain proteins is determined by their binding affinities for c‐di‐GMP
Authors: Pultz Ingrid Swanson , Christen Matthias , Kulasekara Hemantha Don , Kennard Andrew , Kulasekara Bridget , Miller Samuel I. 
Published: November 2012

Summaryc‐di‐GMP is a bacterial second messenger that is enzymatically synthesized and degraded in response to environmental signals. Cellular processes are affected when c‐di‐GMP binds to receptors which include proteins that contain the PilZ domain. Although each c‐di‐GMP synthesis or degradation enzyme metabolizes the same molecule, many of these enzymes can be linked to specific downstream processes. Here we present evidence that c‐di‐GMP signalling specificity is achieved through differences in affinities of receptor macromolecules. We show that the PilZ domain proteins of Salmonella Typhimurium, YcgR and BcsA, demonstrate a 43‐fold difference in their affinity for c‐di‐GMP. Modulation of the affinities of these proteins altered their activities in a predictable manner in vivo. Inactivation of yhjH, which encodes a predicted c‐di‐GMP degrading enzyme, increased the fraction of the cellular population that demonstrated c‐di‐GMP levels high enough to bind to the higher‐affinity YcgR protein and inhibit motility, but not high enough to bind to the lower‐affinity BcsA protein and stimulate cellulose production. Finally, PilZ domain proteins of Pseudomonas aeruginosa demonstrated a 145‐fold difference in binding affinities, suggesting that regulation by binding affinity may be a conserved mechanism that allows organisms with many c‐di‐GMP binding macromolecules to rapidly integrate multiple environmental signals into one output.
Interventions employing mobile technology for overweight and obesity: an early systematic review of randomized controlled trials
Authors: Bacigalupo R. , Cudd P. , Littlewood C. , Bissell P. , Hawley M. S. , Buckley Woods H. 
Published: November 2012

SummaryObesity is a global epidemic with major healthcare implications and costs. Mobile technologies are potential interventions to promote weight loss. An early systematic review of this rapidly growing area of research was conducted. Electronic databases were searched for articles published between January 1998 and October 2011. Data sources included Medline, Embase and the Cochrane Central Register of Controlled Trials. Ongoing research was searched for using clinical trials databases and registers. Out of 174 articles retrieved, 21 met the inclusion criteria of randomized controlled trials (RCTs) on mobile technology interventions facilitating weight loss in overweight and obese adults with any other comparator. A narrative synthesis was undertaken. Seven articles were included and appraised using the Cochrane risk of bias tool: four presented a low risk of bias and three presented a high risk of bias. There is consistent strong evidence across the included multiple high‐quality RCTs that weight loss occurs in the short‐term because of mobile technology interventions, with moderate evidence for the medium‐term. Recommendations for improving the reporting and quality of future trials are made including reporting weight loss in percent to meet clinical standards, and including features such as long‐term follow‐up, cost‐effectiveness and patient acceptability.
Gating of the designed trimeric/tetrameric voltage‐gated H+ channel
Authors: Fujiwara Yuichiro , Kurokawa Tatsuki , Takeshita Kohei , Nakagawa Atsushi , Larsson H. Peter , Okamura Yasushi 
Published: November 2012

Key points
The voltage‐gated H+ channel assembles as a dimer by the cytoplasmic coiled‐coil domain.
This study focuses on understanding the structural characteristics and functional significance of dimerization.
Monomeric, trimeric and tetrameric channels can be engineered by changing the assembly state of the coiled coil by mutation, and interestingly, they show functional currents.
However, only the native dimeric form shows successful cooperative gating, which is of physiological importance in the phagosomal production of reactive oxygen species.
These results help us to understand better why the native form of the channel is a dimer from a standpoint of molecular structure and physiological function.
Abstract  The voltage‐gated H+ channel functions as a dimer, a configuration that is different from standard tetrameric voltage‐gated channels. Each channel protomer has its own permeation pathway. The C‐terminal coiled‐coil domain has been shown to be necessary for both dimerization and cooperative gating in the two channel protomers. Here we report the gating cooperativity in trimeric and tetrameric Hv channels engineered by altering the hydrophobic core sequence of the coiled‐coil assembly domain. Trimeric and tetrameric channels exhibited more rapid and less sigmoidal kinetics of activation of H+ permeation than dimeric channels, suggesting that some channel protomers in trimers and tetramers failed to produce gating cooperativity observed in wild‐type dimers. Multimerization of trimer and tetramer channels were confirmed by the biochemical analysis of proteins, including crystallography. These findings indicate that the voltage‐gated H+ channel is optimally designed as a dimeric channel on a solid foundation of the sequence pattern of the coiled‐coil core, with efficient cooperative gating that ensures sustained and steep voltage‐dependent H+ conductance in blood cells.
Resistance Studies of a Dithiazol Analogue, DBPR110, as a Potential Hepatitis C Virus NS5A Inhibitor in Replicon Systems
Authors: Lin Hui-Mei , Wang Jing-Chyi , Hu Han-Shu , Wu Pei-Shan , Wang Wen-Hung , Wu Su-Ying , Yang Chi-Chen , Yeh Teng-Kuang , Hsu Tsu-An , Jiaang Weir-Torn , Chao Yu-Sheng , Chern Jyh-Haur , Yueh Andrew 
Published: November 2012

ABSTRACTHepatitis C virus (HCV), a member of theFlaviviridaefamily, affects approximately 3% of the world's population and is becoming the leading cause of liver disease in the world. Therefore, the development of novel or more effective treatment strategies to treat chronic HCV infection is urgently needed. In our previous study, we identified a potential HCV NS5A inhibitor, BP008. After further systemic optimization, we discovered a more potent HCV inhibitor, DBPR110. DBPR110 reduced the reporter expression of the HCV1b replicon with a 50% effective concentration (EC50) and a selective index value of 3.9 ± 0.9 pM and >12,800,000, respectively. DBPR110 reduced HCV2a replicon activity with an EC50and a selective index value of 228.8 ± 98.4 pM and >173,130, respectively. Sequencing analyses of several individual clones derived from the DBPR110-resistant RNAs purified from cells harboring genotype 1b and 2a HCV replicons revealed that amino acid substitutions mainly within the N-terminal region (domain I) of NS5A were associated with decreased inhibitor susceptibility. P58L/T and Y93H/N in genotype 1b and T24A, P58L, and Y93H in the genotype 2a replicon were the key substitutions for resistance selection. In the 1b replicon, V153M, M202L, and M265V play a compensatory role in replication and drug resistance. Moreover, DBPR110 displayed synergistic effects with alpha interferon (IFN-α), an NS3 protease inhibitor, and an NS5B polymerase inhibitor. In summary, our results present an effective small-molecule inhibitor, DBPR110, that potentially targets HCV NS5A. DBPR110 could be part of a more effective therapeutic strategy for HCV in the future.
TRIF Mediates Toll-Like Receptor 2-Dependent Inflammatory Responses to Borrelia burgdorferi
Authors: Petnicki-Ocwieja Tanja , Chung Erin , Acosta David I. , Ramos Laurie T. , Shin Ok S. , Ghosh Sanjukta , Kobzik Lester , Li Xin , Hu Linden T. 
Published: November 2012

ABSTRACTTRIF is an adaptor molecule important in transducing signals from intracellularly signaling Toll-like receptor 3 (TLR3) and TLR4. Recently, TLR2 was found to signal from intracellular compartments. Using a synthetic ligand for TLR2/1 heterodimers, as well asBorrelia burgdorferi, which is a strong activator of TLR2/1, we found that TLR2 signaling can utilize TRIF. Unlike TRIF signaling by other TLRs, TLR2-mediated TRIF signaling is dependent on the presence of another adaptor molecule, MyD88. However, unlike MyD88 deficiency, TRIF deficiency does not result in diminished control of infection withB. burgdorferiin a murine model of disease. This appears to be due to the effects of MyD88 on phagocytosis via scavenger receptors, such as MARCO, which are not affected by the loss of TRIF. In mice, TRIF deficiency did have an effect on the production of inflammatory cytokines, suggesting that regulation of inflammatory cytokines and control of bacterial growth may be uncoupled, in part through transduction of TLR2 signaling through TRIF.
The essential elements of health impact assessment and healthy public policy: a qualitative study of practitioner perspectives
Authors: Harris Patrick John , Kemp Lynn Amanda , Sainsbury Peter 
Published: November 2012

ObjectivesThis study uses critical realist methodology to identify the essential and contingent elements of Health Impact Assessment (HIA) and Healthy Public Policy (HPP) as operationalised by practitioners.DesignData collection—qualitative interviews and a workshop were conducted with HIA and HPP practitioners working in differing contexts.Data analysisCritical realist analytical questions identified the essential elements of HIA and HPP, the relationship between them, and the influences of public policy and other contingencies on the practice of both.ParticipantsNine interviews were conducted with purposively sampled participants working in Europe, USA and Australasia. 17 self-selected participants who worked in Europe, South East Asia and Australasia attended the workshop.ResultsThe results clarify that HIA and HPP are different but mutually supporting. HIA has four characteristics: assessing a policy proposal to predict population health and equity impacts, a structured process for stakeholder dialogue, making recommendations and flexibly adapting to the policy process. HPP has four characteristics: concern with a broad definition of health, designing policy to improve people's health and reduce health inequities, intersectoral collaboration and influencing the policy cycle from inception to completion. HIA brings to HPP prediction about a policy's broad health impacts, and a structured space for intersectoral engagement, but is one approach within a broader suite of HPP activities. Five features of public policy and seven contingent influences on HIA and HPP practice are identified.ConclusionsThis study clarifies the core attributes of HIA and HPP as separate yet overlapping while subject to wider influences. This provides the necessary common language to describe the application of both and avoid conflated expectations of either. The findings present the conceptual importance of public policy and the institutional role of public health as distinct and important influences on the practice of HIA and HPP.
Geographical variation in certification rates of blindness and sight impairment in England, 2008–2009
Authors: Malik Aeesha N J , Bunce Catey , Wormald Richard , Suleman Mehrunisha , Stratton Irene , Gray J A Muir 
Published: November 2012

ObjectivesTo examine and interpret the variation in the incidence of blindness and sight impairment in England by PCT, as reported by the Certificate of Vision Impairment (CVI).DesignAnalysis of national certification data.SettingAll Primary Care Trusts, England.Participants23 773 CVI certifications issued from 2008 to 2009.Main Outcome measuresCrude and Age standardised rates of CVI data for blindness and sight loss by PCT.MethodsThe crude and age standardised CVI rates per 100 000 were calculated with Spearman's rank correlation used to assess whether there was any evidence of association between CVI rates with Index of Multiple Deprivation (IMD) and the Programme Spend for Vision.ResultsThere was high-level variation, almost 11-fold (coefficient of variation 38%) in standardised CVI blindness and sight impairment annual certification rates across PCTs. The mean rate was 43.7 and the SD 16.7. We found little evidence of an association between the rate of blindness and sight impairment with either the IMD or Programme Spend on Vision.ConclusionsThe wide geographical variation we found raises questions about the quality of the data and whether there is genuine unmet need for prevention of sight loss. It is a concern for public health practitioners who will be interpreting these data locally and nationally as the CVI data will form the basis of the public health indicator ‘preventable sight loss’. Poor-quality data and inadequate interpretation will only create confusion if not addressed adequately from the outset. There is an urgent need to address the shortcomings of the current data collection system and to educate all public health practitioners.
Genome and Transcriptome Sequencing in Prospective Metastatic Triple-Negative Breast Cancer Uncovers Therapeutic Vulnerabilities
Authors: Craig David W. , O'Shaughnessy Joyce A. , Kiefer Jeffrey A. , Aldrich Jessica , Sinari Shripad , Moses Tracy M. , Wong Shukmei , Dinh Jennifer , Christoforides Alexis , Blum Joanne L. , Aitelli Cristi L. , Osborne Cynthia R. , Izatt Tyler , Kurdoglu Ahmet , Baker Angela , Koeman Julie , Barbacioru Catalin , Sakarya Onur , De La Vega Francisco M. , Siddiqui Asim , Hoang Linh , Billings Paul R. , Salhia Bodour , Tolcher Anthony W. , Trent Jeffrey M. , Mousses Spyro , Von Hoff Daniel , Carpten John D. 
Published: November 2012

Abstract
Triple-negative breast cancer (TNBC) is characterized by the absence of expression of estrogen receptor, progesterone receptor, and HER-2. Thirty percent of patients recur after first-line treatment, and metastatic TNBC (mTNBC) has a poor prognosis with median survival of one year. Here, we present initial analyses of whole genome and transcriptome sequencing data from 14 prospective mTNBC. We have cataloged the collection of somatic genomic alterations in these advanced tumors, particularly those that may inform targeted therapies. Genes mutated in multiple tumors included TP53, LRP1B, HERC1, CDH5, RB1, and NF1. Notable genes involved in focal structural events were CTNNA1, PTEN, FBXW7, BRCA2, WT1, FGFR1, KRAS, HRAS, ARAF, BRAF, and PGCP. Homozygous deletion of CTNNA1 was detected in 2 of 6 African Americans. RNA sequencing revealed consistent overexpression of the FOXM1 gene when tumor gene expression was compared with nonmalignant breast samples. Using an outlier analysis of gene expression comparing one cancer with all the others, we detected expression patterns unique to each patient's tumor. Integrative DNA/RNA analysis provided evidence for deregulation of mutated genes, including the monoallelic expression of TP53 mutations. Finally, molecular alterations in several cancers supported targeted therapeutic intervention on clinical trials with known inhibitors, particularly for alterations in the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR pathways. In conclusion, whole genome and transcriptome profiling of mTNBC have provided insights into somatic events occurring in this difficult to treat cancer. These genomic data have guided patients to investigational treatment trials and provide hypotheses for future trials in this irremediable cancer. Mol Cancer Ther; 12(1); 104–16. ©2012 AACR.
Altar of Words: Text and Ritual in Taittirīya Upaniṣad 2
Authors: Freedman Yitzhak 
Published: November 2012

Abstract
The following study examines the nature and purport of the Upaniṣadic text, focusing on the second chapter of the Taittirīya Upaniṣad. This chapter exhibits structural aspects that parallel those of the brick altar constructed during the Vedic ritual of agnicayana, “piling of the fire-altar.” An analysis of the chapter in light of the interpretations of this ritual in the Brāhmaṇas leads to a new understanding of the text. Rather than being primarily a revelation of doctrine, the text is a manual for a variant, verbalized form of the “piling of the fire-altar.” The verbalized agnicayana includes a ritual construction of the self (ātman) as an altar, created not by bricks, but by the words of the Upaniṣadic text.
Zhang Heng's Huntian yi zhu Revisited
Authors: Lien Y. Edmund 
Published: November 2012

AbstractThe Huntian yi zhu is one of the earliest surviving works on astronomy in ancient China. It is traditionally attributed to Zhang Heng (78-139) of the Eastern Han. Modern scholars have studied the text for the past seven decades and there seems to be agreement on its interpretation, especially on its mathematical contents. This article identifies one major flaw in the assumptions among the modern studies of the piece: the term shao ban, incorrectly taken to mean “one quarter,” should mean “one third.” The mathematical interpretation of the Huntian yi zhu by scholars including Christopher Cullen and Chen Meidong has to be reworked. A new reading is presented here, which demonstrates Zhang Heng's meticulousness on the one hand and our adherence to the philological principle of lectio difficilior potior (the more difficult reading is the stronger) on the other.
New data on the mesopelagic shrimp community of the Canary Islands region
Authors: Landeira J. M. , Fransen C. H. J. M. 
Published: November 2012

During the “ZIFIOCAL 1” cruise, carried out around the islands El Hierro and Tenerife (Canary Islands, NW Africa), at depths between 200 and 750 m, 990 mesopelagic shrimps belonging to 29 species were identified. Many of these species are rare, and therefore the present records constitute new data on their vertical and biogeographical distribution. The collection ofSergia burukovskiirepresents a new record for the Canary Islands. Finally, the first finding ofLigur ensiferusdisplaying a pelagic distribution is also reported.
Creating a ‘We-feeling’ in Heterogeneous Nations: A Cross-country Investigation of the Impact of Inclusion and Autonomy on the National Pride of Ethnic Minorities
Authors: Bühlmann Marc , Hänni Miriam 
Published: November 2012

Abstract
In this contribution, we investigate the impact of different institutions on ethnic minorities’ political support. Based on a hierarchical cross-country comparison, we first show that individuals belonging to ethnic minorities have less national identity than the majority groups within the same country. We then test whether this negative effect of belonging to ethnic minorities can be attenuated by institutions. First, we argue that the inclusion of ethnic minorities by power-sharing institutions gives them the possibility to have a say in politics and, therefore, they develop a sense of common identity. Second, when minority groups are given the autonomy to preserve their group identity, e.g., in federal units, they develop positive feelings for the whole nation and finally a national identity. Our multilevel analyses show that autonomy indeed attenuates the negative effect of minority status on national pride, but that this is not the case for inclusive institutions. In light of increasing heterogeneisation of societies because of migration and denationalization, our findings contribute to the discussion on the relationship between growing ethnic pluralism and good functioning of democratic regimes.
Does Heterogeneity Hinder Democracy?
Authors: Merkel Wolfgang , Weiffen Brigitte 
Published: November 2012

Abstract
Research linking heterogeneity and democracy usually focuses on one single dimension of heterogeneity, such as the distribution of power resources, income inequality, gender inequality, or ethnic fractionalization. Empirical results have so far been inconsistent. This article attempts a sound conceptualization of the phenomenon of heterogeneity. In order to assess whether and how heterogeneity hampers democracy, we will first define what “heterogeneity” means and examine its various dimensions. Then we will discuss why and in which respect heterogeneity constitutes a challenge to democratic transition and consolidation and will review previous research. Our empirical analysis gauges the effect of various dimensions of heterogeneity on the political trajectory of states since the beginning of the third wave of democratization. We find that, while most facets of heterogeneity do not hinder democratic transition, most of them complicate democratic consolidation. Our final discussion offers some suggestions on how the obstacles that heterogeneity poses for democratic development could be overcome and which principles, procedures and institutions are most appropriate to deal with each of the different dimensions of heterogeneity.
Manfredo Tafuri, Fredric Jameson and the Contestations of Political Memory
Authors: Day Gail 
Published: November 2012

Abstract
The Italian architectural historian Manfredo Tafuri (1935–94) developed a distinctive Marxist approach of critical analysis, which has prompted extensive responses. The reception of his work in the United States in the 1970s and 80s – the intervention of Fredric Jameson, especially – forms an important moment of historiographical mutation, in which the status of Tafuri’s politics holds an intriguing place: it was eviscerated in the very act of its affirmation. At stake is not simply the problems attending the transatlantic migration of a body of architectural theory, but also a question lying at the heart of Tafuri’s analysis: the problems of achieving social reforms, above all, in ‘working-class housing’. The difficulties encountered by projects to improve accommodation – from Weimar Germany and Red Vienna in the 1920s to the programmes of postwar Italy – provide the concrete material for Tafuri’s analysis while remaining a significant blind-spot within most of the commentary. Tafuri is here reappraised in the light of the political debates over the ‘neorealist architecture’ of the 1950s and the reform-policies of the Italian centre-Left in the early 1960s. Proceeding as if this formative moment never happened, Tafuri’s critics often engage in debates which confuse his critique of the building projects with political despair, and which appeal to enclave-building despite Tafuri’s explicit questioning of such strategies.
The Path Not Taken: French Industrialization in the Age of Revolution, 1750–1830, Jeff Horn, Cambridge, MA.: MIT Press, 2006
Authors: Heller Henry 
Published: November 2012

AbstractEschewing a Marxist interpretation of the French Revolution, Jeff Horn’s work is nonetheless interesting in stressing the widespread prevalence of machine-breaking by workers in France as compared to England during industrialisation. Likewise notable is Horn’s argument that the resultant state-intervention forced France onto a path of industrialisation which differed from England’s and which has been underestimated. Breaking with the revisionist consensus, Horn further demonstrates that the effect of the Revolution was positive for French economic development. Refreshing in its stress on working-class militancy, Horn’s work nonetheless exaggerates the influence of machine-breaking on French economic change as compared to other forms of working-class struggle, the slow pace of primitive accumulation and the resistance to industrialisation by small-scale urban producers.