bluuebunny/crossref_metadata_2025 huggingface dataset:
Whose carbon is burnable? Equity considerations in the allocation of a “right to extract”
Authors: Kartha Sivan , Caney Simon , Dubash Navroz K. , Muttitt Greg
Published: May 2018

Carbon emissions—and hence fossil fuel combustion—must decline rapidly if warming is to be held below 1.5 or 2 °C. Yet fossil fuels are so deeply entrenched in the broader economy that a rapid transition poses the challenge of significant transitional disruption. Fossil fuels must be phased out even as access to energy services for basic needs and for economic development expands, particularly in developing countries. Nations, communities, and workers that are economically dependent on fossil fuel extraction will need to find a new foundation for livelihoods and revenue. These challenges are surmountable. In principle, societies could undertake a decarbonization transition in which they anticipate the transitional disruption, and cooperate and contribute fairly to minimize and alleviate it. Indeed, if societies do not work to avoid that disruption, a decarbonization transition may not be possible at all. Too many people may conclude they will suffer undue hardship, and thus undermine the political consensus required to undertake an ambitious transition. The principles and framework laid out here are offered as a contribution to understanding the nature of the potential impacts of a transition, principles for equitably sharing the costs of avoiding them, and guidance for prioritizing which fossil resources can still be extracted.
Nuclear factor‐kappa B: Glucocorticoid‐induced leucine zipper interface analogs suppress pathology in an Alzheimer's disease model
Authors: Srinivasan Mythily , Lahiri Niloy , Thyagarajan Anish , Witek Emily , Hickman Debra , Lahiri Debomoy K.
Published: May 2018

Introduction

Glucocorticoid‐induced leucine zipper is a regulatory protein that sequesters activated nuclear factor‐kappa B p65. Previously, we showed that rationally designed analogs of the p65‐binding domain of glucocorticoid‐induced leucine zipper, referred to as glucocorticoid‐induced leucine zipper analogs (GAs), inhibited amyloid β–induced metabolic activity and inflammatory cytokines in mixed brain cell cultures. Here, we investigate the therapeutic efficacy of GA in an Alzheimer's disease model.

Methods

GA and control peptides were synthesized covalently as peptide amides with the cell‐penetrating agent. C57Bl/6J mice induced with lipopolysaccharide‐mediated neuroinflammation (250 mg/kg i.p/day for six days) were treated on alternate days with GA‐1, GA‐2, or control peptides (25 mg/kg i.v). Brain tissues were assessed for gliosis, cytokines, and antiapoptotic factors.

Results

The brain tissues of GA‐1– and GA‐2–treated mice exhibited significantly reduced gliosis, suppressed inflammatory cytokines, and elevated antiapoptotic factors.

Discussion

The antineuroinflammatory effects of GA suggest potential therapeutic application for Alzheimer's disease.
The Mediating Relationship Between Maladaptive Behaviours, Cognitive Factors, and Generalised Anxiety Disorder Symptoms
Authors: Mahoney Alison E.J. , Hobbs Megan J. , Williams Alishia D. , Andrews Gavin , Newby Jill M.
Published: May 2018

Cognitive theories of generalised anxiety disorder (GAD) posit that cognitive and behavioural factors maintain the disorder. This study examined whether avoidance and safety behaviours mediated the relationship between cognitive factors and GAD symptoms. We also examined the reverse mediation model; that is, whether cognitive factors mediated the relationship between maladaptive behaviours and GAD symptoms. Undergraduate psychology students (N = 125 and N = 292) completed the Worry Behaviours Inventory (a recently developed measure of maladaptive behaviours associated with GAD), in addition to measures of intolerance of uncertainty, cognitive avoidance, metacognitive beliefs, and symptoms of GAD and depression. Analyses supported the reliability and validity of the WBI. We consistently found that engagement in maladaptive behaviours significantly mediated the relationship between cognitive factors and symptoms of GAD. The reverse mediation model was also supported. Our results are consistent with the contention that cognitive and behavioural factors contribute to GAD symptom severity.
The Perils of “Turkish Presidentialism”
Authors: Esen Berk , Gumuscu Sebnem
Published: May 2018

Turkey has switched to a presidential system via a referendum held in April 2017 that will take full effect after the 2019 presidential elections. Turkish presidentialism increases the prominence of the executive at the expense of the legislative branch and concentrates power in the office of the president. Executive aggrandizement will deepen ideological polarization and electoral mobilization by significantly raising the stakes of the game for both the incumbent and the opposition. As such, we posit that the new presidential system will institutionalize the de facto personalism and majoritarian rule that the AKP has hitherto established in recent years. This trend is likely to trigger a transition from a competitive authoritarian to hegemonic electoral authoritarianism in case of Tayyip Erdoğan's election, thus placing Turkey on par with the strongest executive systems around the globe such as Russia and Venezuela.
Rula Quawas 1960–2017
Authors: Sabbagh Amal
Published: May 2018

On 25 July 2017, Jordan lost one of its great educators and feminists: Rula Quawas. Rula was an outstanding educator for generations of young Jordanian and Arab feminists. She took on challenges that no one else dared to approach in a conservative patriarchal society, knowing fully well that she might have to pay a dear personal price for each of these battles.
Cheryl A. Rubenberg 1946–2017
Authors: Hoffman Valerie J.
Published: May 2018

Cheryl A. Rubenberg, independent analyst and former associate professor of political science at Florida International University, died on 16 June 2017 at age seventy-one. Born and raised in Pennsylvania, she earned her bachelor's in political science from Hunter College, her master's in international relations from Johns Hopkins University, and her Ph.D. in international relations from the University of Miami (1979). After a year at Florida Atlantic University, she joined the political science faculty at Florida International University. A student who took her class on American government wrote that Professor Rubenberg “changed my life forever” by exposing the business interests that motivate leaders of American government and media.
Jack G. Shaheen 1935–2017
Authors: Tchen John Kuo Wei
Published: May 2018

Pioneering author and media critic, Dr. Jack Shaheen devoted his life to identifying and contesting damaging stereotypes of Arabs and Muslims in American media and pop culture. Arabs and Muslims were offered up as cartoon caricatures—dagger wielding, evil, ridiculous, hypersexualized, inhumane and incompetent “others.” Dr. Shaheen quickly recognized their shared genealogy to the portrayals of other racialized groups including Jews, Native Americans, Asian Americans, Latinos, and African Americans. Always in the spirit of engaged dialogue, he was outspoken in defense of any group that was wrongfully stereotyped and vilified.
From Extremism to Terrorism: The Radicalisation of the Far Right in Italy and West Germany
Authors: HOF TOBIAS
Published: May 2018

Since the 1960s in Italy and Germany the notion has prevailed that ‘the state’ has given support to right-wing terrorism. This article challenges such views by examining the internal dynamics of right-wing terrorism in both countries with reference to Ehud Sprinzak's theory of ‘split delegitimisation’. To explain the different scale of Italian and West German terrorism one must analyse personnel continuities, the nature of the perceived ‘communist threat’, as well as the national political culture. Thus, without neglecting state support for the far right, this article emphasises how the internal dynamics of terrorist groups respond to political and social frameworks. Only if we acknowledge that right-wing terrorist groups possess their own agency can we fully understand their development. This is even more urgent in a time when – once again – the far right is on the rise in Europe.
Spontaneous Version of Fetal Presentation in Twin Pregnancies During Third Trimester: Longitudinal Assessment
Authors: Park Jeong Woo , Lee Seung Mi , Kang Hye-Sim , Shim Soon-Sup , Jun Jong Kwan
Published: May 2018

Little is known about longitudinal changes of the first twin presentation in twin gestations. This is a retrospective cohort study including 411 women who were admitted consecutively and delivered live-born twins at 36 weeks of gestation or more. Longitudinal assessment of the first twin presentation was conducted during gestation and at birth in all cases. Gestational age at antenatal assessment was divided into two intervals: early-third trimester (28–31 weeks) and mid-third trimester (32–35 weeks). Fetal presentation was categorized as vertex or non-vertex. We analyzed change of fetal presentation between antepartum intervals and birth. First twin presentation at early-third trimester had the same presentation at birth in 87.6% (360/411) of the study population. In this ‘no change’ group, vertex presentation was seen in 95.6% (283/296) and non-vertex was seen in 67.0% (77/115) of cases. In total, 96.1% (395/411) of the study population maintained their presentation between mid-third trimester and birth. Vertex presentation was seen in 98.4% (310/315) and non-vertex was seen in 88.5% (85/96) of cases. When comparing vertex with non-vertex, vertex presentation during third trimester was a more reliable predictor of presentation at birth (p < .001). The only factor that contributed significantly to spontaneous version of the first twin during mid-third trimester and birth was a lower birth weight of the first twin compared with the second twin. In conclusion, first twin presentation with vertex during third trimester is not likely to change into non-vertex at birth. We concluded that vertex presentation in twin gestations at early- and mid-third trimester is very predictable. In contrast, a non-vertex first twin presentation is relatively unstable.
Geomorphology of Scour Holes at Tidal Channel Confluences
Authors: Ferrarin Christian , Madricardo Fantina , Rizzetto Federica , Kiver William Mc , Bellafiore Debora , Umgiesser Georg , Kruss Aleksandra , Zaggia Luca , Foglini Federica , Ceregato Alessandro , Sarretta Alessandro , Trincardi Fabio
Published: May 2018

The morphology of scour holes at tidal channel confluences was investigated through high‐resolution acoustic mapping of the channel network in the Venice Lagoon (Italy). Our investigation identified 29 confluence scours ranging in depth from 7 to 26 m and characterized by different confluence geometry and scour properties. Scours were found at the confluence of two or more channels, having equal or unequal bed heights and a diverse confluence planform geometry. The main morphological characteristics of the scours were compared to literature data from fluvial environments. Like in rivers, the scour depth tends to increase with the angle of the confluence. Moreover, the maximum depth of the confluence scours in the Venice Lagoon is positively correlated with the tidal prism of the channels joining the confluence. The investigation of the seafloor features in the scour holes highlighted that, generally, small‐ and medium‐scale bedforms are present on the gentle slope. The scours' seafloor roughness indicated that in tidal channels both ebb and flood flows combine in shaping the confluence morphology. In addition, the analysis of historical bathymetric datasets dating back to the 1800s allowed us to analyze the morphological evolution of two of these erosive features. Our findings revealed the century‐scale morphological dynamics of scour holes, as a consequence of changes in the flow regime.
Magma Flow in a Major Icelandic Eruption
Authors: Stanley Sarah
Published: May 2018

Mechanical modeling suggests that previous, undetected eruptions released tectonic stress near the ice-covered B�r�arbunga volcano.
Signatures of Reductive Magnetic Mineral Diagenesis From Unmixing of First‐Order Reversal Curves
Authors: Roberts Andrew P. , Zhao Xiang , Harrison Richard J. , Heslop David , Muxworthy Adrian R. , Rowan Christopher J. , Larrasoaña Juan‐Cruz , Florindo Fabio
Published: May 2018

Diagenetic alteration of magnetic minerals occurs in all sedimentary environments and tends to be severe in reducing environments. Magnetic minerals provide useful information about sedimentary diagenetic processes, which makes it valuable to use magnetic properties to identify the diagenetic environment in which the magnetic minerals occur and to inform interpretations of paleomagnetic recording or environmental processes. We use a newly developed first‐order reversal curve unmixing method on well‐studied samples to illustrate how magnetic properties can be used to assess diagenetic processes in reducing sedimentary environments. From our analysis of multiple data sets, consistent magnetic components are identified for each stage of reductive diagenesis. Relatively unaltered detrital and biogenic magnetic mineral assemblages in surficial oxic to manganous diagenetic environments undergo progressive dissolution with burial into ferruginous and sulfidic environments and largely disappear at the sulfate‐methane transition. Below the sulfate‐methane transition, a weak superparamagnetic to largely noninteracting stable single domain (SD) greigite component is observed in all studied data sets. Moderately interacting stable SD authigenic pyrrhotite and strongly interacting stable SD greigite are observed commonly in methanic environments. Recognition of these characteristic magnetic components enables identification of diagenetic processes and should help to constrain interpretation of magnetic mineral assemblages in future studies. A key question for future studies concerns whether stable SD greigite forms in the sulfidic or methanic zones, where formation in deeper methanic sediments will cause greater delays in paleomagnetic signal recording. Authigenic pyrrhotite forms in methanic environments, so it will usually record a delayed paleomagnetic signal.
Update on glycerol-3-phosphate acyltransferases: the roles in the development of insulin resistance
Authors: Yu Jing , Loh Kim , Song Zhi-yuan , Yang He-qin , Zhang Yi , Lin Shu
Published: May 2018

Glycerol-3-phosphate acyltransferase (GPAT) is the rate-limiting enzyme in the de novo pathway of glycerolipid synthesis. It catalyzes the conversion of glycerol-3-phosphate and long-chain acyl-CoA to lysophosphatidic acid. In mammals, four isoforms of GPATs have been identified based on subcellular localization, substrate preferences, and NEM sensitivity, and they have been classified into two groups, one including GPAT1 and GPAT2, which are localized in the mitochondrial outer membrane, and the other including GPAT3 and GPAT4, which are localized in the endoplasmic reticulum membrane. GPATs play a pivotal role in the regulation of triglyceride and phospholipid synthesis. Through gain-of-function and loss-of-function experiments, it has been confirmed that GPATs play a critical role in the development of obesity, hepatic steatosis, and insulin resistance. In line with this, the role of GPATs in metabolism was supported by studies using a GPAT inhibitor, FSG67. Additionally, the functional characteristics of GPATs and the relation between three isoforms (GPAT1, 3, and 4) and insulin resistance has been described in this review.
Associations of serum indolepropionic acid, a gut microbiota metabolite, with type 2 diabetes and low-grade inflammation in high-risk individuals
Authors: Tuomainen Marjo , Lindström Jaana , Lehtonen Marko , Auriola Seppo , Pihlajamäki Jussi , Peltonen Markku , Tuomilehto Jaakko , Uusitupa Matti , de Mello Vanessa D. , Hanhineva Kati
Published: May 2018

We recently reported using non-targeted metabolic profiling that serum indolepropionic acid (IPA), a microbial metabolite of tryptophan, was associated with a lower likelihood of developing type 2 diabetes (T2D). In the present study, we established a targeted quantitative method using liquid chromatography with mass spectrometric detection (HPLC-QQQ-MS/MS) and measured the serum concentrations of IPA in all the participants from the Finnish Diabetes Prevention Study (DPS), who had fasting serum samples available from the 1-year study follow-up (n = 209 lifestyle intervention and n = 206 control group). Higher IPA at 1-year study was inversely associated with the incidence of T2D (OR [CI]: 0.86 [0.73–0.99], P = 0.04) and tended to be directly associated with insulin secretion (β = 0.10, P = 0.06) during the mean 7-year follow-up. Moreover, IPA correlated positively with dietary fiber intake (g/day: r = 0.24, P = 1 × 10−6) and negatively with hsCRP concentrations at both sampling (r = − 0.22, P = 0.0001) and study follow-up (β = − 0.19, P = 0.001). Thus, we suggest that the putative effect of IPA on lowering T2D risk might be mediated by the interplay between dietary fiber intake and inflammation or by direct effect of IPA on β-cell function.
Beyond the tip of the iceberg; a new view of the diversity of sulfite- and sulfate-reducing microorganisms
Authors: Vigneron Adrien , Cruaud Perrine , Alsop Eric , de Rezende Julia R , Head Ian M , Tsesmetzis Nicolas
Published: May 2018

Sulfite-reducing and sulfate-reducing microorganisms (SRM) play important roles in anoxic environments, linking the sulfur and carbon cycles. With climate warming, the distribution of anoxic habitats conductive to dissimilatory SRM is expanding. Consequently, we hypothesize that novel SRM are likely to emerge from the rare biosphere triggered by environmental changes. Using the dsrB gene as a  molecular marker of sulfite-reducers and sulfate-reducers, we analyzed the diversity, community composition, and abundance of SRM in 200 samples representing 14 different ecosystems, including marine and freshwater environments, oil reservoirs, and engineered infrastructure. Up to 167,397 species-level OTUs affiliated with 47 different families were identified. Up to 96% of these can be considered as “rare biosphere SRM”. One  third of the dsrB genes identified belonged to uncharacterized lineages. The dsrB sequences exhibited a  strong pattern of selection in different ecosystems. These results expand our knowledge of the biodiversity and distribution of SRM, with implications for carbon and sulfur cycling in anoxic ecosystems.
Convergent roles of de novo mutations and common variants in schizophrenia in tissue-specific and spatiotemporal co-expression network
Authors: Jia Peilin , Chen Xiangning , Fanous Ayman H. , Zhao Zhongming
Published: May 2018

Genetic components susceptible to complex disease such as schizophrenia include a wide spectrum of variants, including common variants (CVs) and de novo mutations (DNMs). Although CVs and DNMs differ by origin, it remains elusive whether and how they interact at the gene, pathway, and network levels that leads to the disease. In this work, we characterized the genes harboring schizophrenia-associated CVs (CVgenes) and the genes harboring DNMs (DNMgenes) using measures from network, tissue-specific expression profile, and spatiotemporal brain expression profile. We developed an algorithm to link the DNMgenes and CVgenes in spatiotemporal brain co-expression networks. DNMgenes tended to have central roles in the human protein–protein interaction (PPI) network, evidenced in their high degree and high betweenness values. DNMgenes and CVgenes connected with each other significantly more often than with other genes in the networks. However, only CVgenes remained significantly connected after adjusting for their degree. In our gene co-expression PPI network, we found DNMgenes and CVgenes connected in a tissue-specific fashion, and such a pattern was similar to that in GTEx brain but not in other GTEx tissues. Importantly, DNMgene–CVgene subnetworks were enriched with pathways of chromatin remodeling, MHC protein complex binding, and neurotransmitter activities. In summary, our results unveiled that both DNMgenes and CVgenes contributed to a core set of biologically important pathways and networks, and their interactions may attribute to the risk for schizophrenia. Our results also suggested a stronger biological effect of DNMgenes than CVgenes in schizophrenia.
Correction to: Disease-linked connexin26 S17F promotes volar skin abnormalities and mild wound healing defects in mice
Authors: Press Eric , Alaga Katanya C , Barr Kevin , Shao Qing , Bosen Felicitas , Willecke Klaus , Laird Dale W
Published: May 2018

Correction to:NPG Asia Materials (2018) https://doi.org/10.1038/s41427-018-0014-9 published online on 16 April 2018
HMGB1 released from intestinal epithelia damaged by cholera toxin adjuvant contributes to activation of mucosal dendritic cells and induction of intestinal cytotoxic T lymphocytes and IgA
Authors: Wakabayashi Ayako , Shimizu Masumi , Shinya Eiji , Takahashi Hidemi
Published: May 2018

Cholera toxin (CT) is a potent mucosal adjuvant and oral administration of ovalbumin (OVA) antigens plus CT induces OVA-specific CD8+cytotoxic T lymphocytes (CTLs) and IgA production in intestinal mucosa. However, the mechanisms of induction of these immune responses remain unknown. Intestinal OVA-specific CD8+CTLs were not induced by oral administration of the CT active (CTA) or CT binding (CTB) subunit as an adjuvant and CD11c+DCs were involved in cross-priming of intestinal CTLs. CD8+CD103+CD11c+CD11b−DCs and DCIR2+CD103+CD11c+CD11b+DCs were distributed in the intestinal lamina propria and mesenteric lymph nodes, both DC subsets expressed DEC-205, and the expression of co-stimulatory molecules such as CD80 and CD86 was enhanced in both DC subsets after oral administration of intact CT but not the CTA or CTB subunit. Intestinal DCs activated by the oral administration of OVA plus CT cross-presented OVA antigens and DCs that captured OVA antigen through DEC-205, but not DCIR2, could cross-present antigen. We found that oral administration of intact CT, but not the CTA or CTB subunit, enhanced cell death, cytoplasmic expression of high-mobility group box 1 protein (HMGB1) in epithelial cell adhesion molecule (EpCAM)+CD45−intestinal epithelial cells (IECs), and HMGB1 levels in fecal extracts. HMGB1 dose-dependently enhanced the expression of CD80 and CD86 on DCs in vitro, and intravenous or oral administration of glycyrrhizin, an HMGB1 inhibitor, significantly suppressed activation of mucosal DCs and induction of intestinal OVA-specific CTLs and IgA by oral CT administration. These results showed that oral administration of intact CT triggers epithelial cell death in the gut and the release of HMGB1 from damaged IECs, and that the released HMGB1 may mediate activation of mucosal DCs and induction of CTLs and IgA in the intestine.
MicroRNA regulation of the MRN complex impacts DNA damage, cellular senescence, and angiogenic signaling
Authors: Espinosa-Diez Cristina , Wilson RaeAnna , Chatterjee Namita , Hudson Clayton , Ruhl Rebecca , Hipfinger Christina , Helms Erin , Khan Omar F. , Anderson Daniel G. , Anand Sudarshan
Published: May 2018

MicroRNAs (miRs) contribute to biological robustness by buffering cellular processes from external perturbations. Here we report an unexpected link between DNA damage response and angiogenic signaling that is buffered by a miR. We demonstrate that genotoxic stress-induced miR-494 inhibits the DNA repair machinery by targeting the MRE11a-RAD50-NBN (MRN) complex. Gain- and loss-of-function experiments show that miR-494 exacerbates DNA damage and drives endothelial senescence. Increase of miR-494 affects telomerase activity, activates p21, decreases pRb pathways, and diminishes angiogenic sprouting. Genetic and pharmacological disruption of the MRN pathway decreases VEGF signaling, phenocopies miR-494-induced senescence, and disrupts angiogenic sprouting. Vascular-targeted delivery of miR-494 decreases both growth factor-induced and tumor angiogenesis in mouse models. Our work identifies a putative miR-facilitated mechanism by which endothelial cells can be insulated against VEGF signaling to facilitate the onset of senescence and highlight the potential of targeting DNA repair to disrupt pathological angiogenesis.
Design principles for electronic charge transport in solution-processed vertically stacked 2D perovskite quantum wells
Authors: Tsai Hsinhan , Asadpour Reza , Blancon Jean-Christophe , Stoumpos Constantinos C. , Even Jacky , Ajayan Pulickel M. , Kanatzidis Mercouri G. , Alam Muhammad Ashraful , Mohite Aditya D. , Nie Wanyi
Published: May 2018

State-of-the-art quantum-well-based devices such as photovoltaics, photodetectors, and light-emission devices are enabled by understanding the nature and the exact mechanism of electronic charge transport. Ruddlesden–Popper phase halide perovskites are two-dimensional solution-processed quantum wells and have recently emerged as highly efficient semiconductors for solar cell approaching 14% in power conversion efficiency. However, further improvements will require an understanding of the charge transport mechanisms, which are currently unknown and further complicated by the presence of strongly bound excitons. Here, we unambiguously determine that dominant photocurrent collection is through electric field-assisted electron–hole pair separation and transport across the potential barriers. This is revealed by in-depth device characterization, coupled with comprehensive device modeling, which can self-consistently reproduce our experimental findings. These findings establish the fundamental guidelines for the molecular and device design for layered 2D perovskite-based photovoltaics and optoelectronic devices, and are relevant for other similar quantum-confined systems.
Crystal step edges can trap electrons on the surfaces of n-type organic semiconductors
Authors: He Tao , Wu Yanfei , D’Avino Gabriele , Schmidt Elliot , Stolte Matthias , Cornil Jérôme , Beljonne David , Ruden P. Paul , Würthner Frank , Frisbie C. Daniel
Published: May 2018

Understanding relationships between microstructure and electrical transport is an important goal for the materials science of organic semiconductors. Combining high-resolution surface potential mapping by scanning Kelvin probe microscopy (SKPM) with systematic field effect transport measurements, we show that step edges can trap electrons on the surfaces of single crystal organic semiconductors. n-type organic semiconductor crystals exhibiting positive step edge surface potentials display threshold voltages that increase and carrier mobilities that decrease with increasing step density, characteristic of trapping, whereas crystals that do not have positive step edge surface potentials do not have strongly step density dependent transport. A device model and microelectrostatics calculations suggest that trapping can be intrinsic to step edges for crystals of molecules with polar substituents. The results provide a unique example of a specific microstructure–charge trapping relationship and highlight the utility of surface potential imaging in combination with transport measurements as a productive strategy for uncovering microscopic structure–property relationships in organic semiconductors.
Adjuvant composition and delivery route shape immune response quality and protective efficacy of a recombinant vaccine for Entamoeba histolytica
Authors: Abhyankar Mayuresh M. , Orr Mark T. , Lin Susan , Suraju Mohammed O. , Simpson Adrian , Blust Molly , Pham Tiep , Guderian Jeffrey A. , Tomai Mark A. , Elvecrog James , Pedersen Karl , Petri William A. , Fox Christopher B.
Published: May 2018

Amebiasis caused by Entamoeba histolytica is the third leading cause of parasitic mortality globally, with some 100,000 deaths annually, primarily among young children. Protective immunity to amebiasis is associated with fecal IgA and IFN-γ in humans; however, no vaccine exists. We have previously identified recombinant LecA as a potential protective vaccine antigen. Here we describe the development of a stable, manufacturable PEGylated liposomal adjuvant formulation containing two synthetic Toll-like receptor (TLR) ligands: GLA (TLR4) and 3M-052 (TLR7/8). The liposomes stimulated production of monocyte/macrophage chemoattractants MCP-1 and Mip-1β, and Th1-associated cytokines IL-12p70 and IFN-γ from human whole blood dependent on TLR ligand composition and dose. The liposomes also demonstrated acceptable physicochemical compatibility with the recombinant LecA antigen. Whereas mice immunized with LecA and GLA-liposomes demonstrated enhanced antigen-specific fecal IgA titers, mice immunized with LecA and 3M-052-liposomes showed a stronger Th1 immune profile. Liposomes containing GLA and 3M-052 together elicited both LecA-specific fecal IgA and Th1 immune responses. Furthermore, the quality of the immune response could be modulated with modifications to the liposomal formulation based on PEG length. Compared to subcutaneous administration, the optimized liposome adjuvant composition with LecA antigen administered intranasally resulted in significantly enhanced fecal IgA, serum IgG2a, as well as systemic IFN-γ and IL-17A levels in mice. The optimized intranasal regimen provided greater than 80% protection from disease as measured by parasite antigen in the colon. This work demonstrates the physicochemical and immunological characterization of an optimized mucosal adjuvant system containing a combination of TLR ligands with complementary activities and illustrates the importance of adjuvant composition and route of delivery to enhance a multifaceted and protective immune response to amebiasis.
Sensitivity of Transmission Raman Spectroscopy Signals to Temperature of Biological Tissues
Authors: Ghita Adrian , Matousek Pavel , Stone Nick
Published: May 2018

Optical properties of biological tissues can be influenced by their temperature, thus affecting light transport inside the sample. This could potentially be exploited to deliver more photons inside large biological samples, when compared with experiments at room temperature, overcoming some of difficulties due to highly scattering nature of the tissue. Here we report a change in light transmitted inside biological tissue with temperature elevation from 20 to 40 °C, indicating a considerable enhancement of photons collected by the detector in transmission geometry. The measurement of Raman signals in porcine tissue samples, as large as 40 mm in thickness, indicates a considerable increase in signal ranging from 1.3 to 2 fold, subject to biological variability. The enhancements observed are ascribed to phase transitions of lipids in biological samples. This indicates that: 1) experiments performed on tissue at room temperature can lead to an underestimation of signals that would be obtained at depth in the body in vivo and 2) that experiments at room temperature could be modified to increase detection limits by elevating the temperature of the material of interest.
Ocean acidification promotes otolith growth and calcite deposition in gilthead sea bream (Sparus aurata) larvae
Authors: Coll-Lladó Clara , Giebichenstein Jan , Webb Paul B. , Bridges Christopher R. , de la serrana Daniel Garcia
Published: May 2018

The effects of ocean acidification on otolith crystallization and growth rates were investigated in gilthead sea bream (Sparus aurata) larvae. Larvae were exposed to three different pH levels: pH8.2, pH7.7 and pH7.3 for a period of 18 days post-fertilization. For the first time, we demonstrate that pH has a significant impact on the carbonate polymorph composition, showing calcite in a significant percentage of individuals at low pH. Around 21% of the larvae exposed to pH7.3 showed irregular calcitic otoliths rather than commonly found round aragonitic otoliths. Calcitic otoliths showed a moderate level of heritability suggesting an important role of genetic factors. We also observed significantly larger otoliths in larvae reared at pH7.7 and pH7.3 compared to pH8.2 in both sagittae and lapilli. Our results demonstrate that otolith growth rates in gilthead sea bream larvae increase at low pH while a significant proportion of larvae are prone to the formation of calcitic otoliths at pH7.3.
Oncological outcomes, quality of life outcomes and complications of partial cystectomy for selected cases of muscle-invasive bladder cancer
Authors: Ebbing Jan , Heckmann Robin Colja , Collins Justin William , Miller Kurt , Erber Barbara , Friedersdorff Frank , Fuller Tom Florian , Busch Jonas , Seifert Hans Helge , Ardelt Peter , Wetterauer Christian , Hosseini Abolfazl , Jentzmik Florian , Kempkensteffen Carsten
Published: May 2018

To evaluate the oncological results, associated complications, and postoperative health-related quality of life (HR-QoL) in patients treated with partial cystectomy (PC) for muscle-invasive bladder cancer (MIBC). 27 patients who underwent open PC for cT2 MIBC were included. A simple Cox’s proportional hazards regression model was used to assess the association of several potential prognostic factors with survival. Postoperative HR-QoL was assessed with the EORTC (European Organisation for the Research and Treatment of Cancer) QLQ-C30 questionnaire version 3.0. Final pathological tumour stages in PC specimen were: pT0: 18.5%, non-MIBC: 3.7%, MIBC: 74.1%, pCIS: 14.8%. Estimated 5-year overall- and progression-free survival rates were 53.7% and 62.1%. Five (18.5%) patients experienced local recurrence with MIBC. Overall, the salvage cystectomy rate was 18.5%. The 90-day mortality rate was 0%. Significant risk factors for progression-free survival were vascular invasion (HR 5.33) and tumour multilocularity (HR 4.5) in the PC specimen, and a ureteric reimplantation during PC (HR 4.53). The rates of intraoperative complications, 30- and 90-day major complications were 7.4%, respectively and 14.8% for overall long-term complications. Postoperatively, median (IQR) global health status and QoL in our PC cohort was 79.2 (52.1–97.9). Open PC can provide adequate cancer control of MIBC with good HR-QoL in highly selected cases. Open PC can lead to long-term bladder preservation and shows an acceptable rate of severe perioperative complications, even in highly comorbid patients.
Author Correction: The Staphylococcus aureus extracellular matrix protein (Emp) has a fibrous structure and binds to different extracellular matrices
Authors: Geraci Jennifer , Neubauer Svetlana , Pöllath Christine , Hansen Uwe , Rizzo Fabio , Krafft Christoph , Westermann Martin , Hussain Muzaffar , Peters Georg , Pletz Mathias W. , Löffler Bettina , Makarewicz Oliwia , Tuchscherr Lorena
Published: May 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
A Rapid, Accurate, Single Molecule Counting Method Detects Clostridium difficile Toxin B in Stool Samples
Authors: Gite Sadanand , Archambault Destiny , Cappillino Michael P. , Cunha David , Dorich Victoria , Shatova Tatyana , Tempesta Andrew , Walsh Bruce , Walsh Jessica A. , Williams Adam , Kirby James E. , Bowers Jayson , Straus Don
Published: May 2018

We describe a new rapid and accurate immunoassay-based technology capable of counting single target molecules using digital imaging without magnification. Using the technology, we developed a rapid test for Clostridium difficile toxin B, which is responsible for the pathology underlying potentially fatal C. difficile infections (CDI). There are currently no tests for CDI that are rapid, sensitive, and specific. The MultiPath C. difficile toxin B test images and counts complexes of target-specific magnetic and fluorescent particles that have been tethered together by toxin B molecules in minimally processed stool samples. The performance characteristics of the 30 minute test include a limit of detection of 45 pg/mL, dynamic range covering 4–5 orders of magnitude, and coefficient of variation of less than 10%. The MultiPath test detected all toxinotypes and ribotypes tested, including the one most commonly occurring in the US and EU; shows no cross reactivity with relevant bacterial species; and is robust to potential interferants commonly present in stool samples. On a training set of 320 clinical stool samples, the MultiPath C. difficile toxin B test showed 97.0% sensitivity (95% CI, 91.4–99.4%); 98.3% specificity (95% CI, 96.8–99.2%); and 98.2% accuracy (95% CI, 96.7–99.0%) compared to the cellular cytotoxicity neutralization assay (CCNA) reference method. Based on these compelling performance characteristics, we believe the MultiPath technology can address the lack of rapid, sensitive, specific, and easy-to-use diagnostic tests for C. difficile.
Normal pre-attentive and impaired attentive processing of lexical tones in Cantonese-speaking congenital amusics
Authors: Zhang Caicai , Shao Jing
Published: May 2018

The neural underpinnings of congenital amusia, an innate neurogenetic disorder of musical pitch processing, are not well understood. Previous studies suggest that amusia primarily impairs attentive processing (P300) of small pitch deviations in music, leaving pre-attentive pitch processing (mismatch negativity or MMN) more or less intact. However, it remains unknown whether the same neuro-dynamic mechanism of deficiency underlies pitch processing in speech, where amusics also often show impairment behaviorally. The current study examined how lexical tones are processed in pre-attentive (MMN) and attentive (P300) conditions in 24 Cantonese-speaking amusics and 24 matched controls. At the pre-attentive level, Cantonese-speaking amusics exhibited normal MMN responses to lexical tone changes, even for tone pairs with small pitch differences (mid level vs. low level tone; high rising vs. low rising tone). However, at the attentive level, amusics exhibited reduced P3a amplitude for all tone pairs, and further reduced P3b amplitude for tone pairs with small pitch differences. These results suggest that the amusic brain detects tone changes normally pre-attentively, but shows impairment in consciously detecting the same tone differences. Consistent with previous findings in nonspeech pitch processing, this finding provides support for a domain-general neuro-dynamic mechanism of deficient attentive pitch processing in amusia.
Decellularised skeletal muscles allow functional muscle regeneration by promoting host cell migration
Authors: Urciuolo Anna , Urbani Luca , Perin Silvia , Maghsoudlou Panagiotis , Scottoni Federico , Gjinovci Asllan , Collins-Hooper Henry , Loukogeorgakis Stavros , Tyraskis Athanasios , Torelli Silvia , Germinario Elena , Fallas Mario Enrique Alvarez , Julia-Vilella Carla , Eaton Simon , Blaauw Bert , Patel Ketan , De Coppi Paolo
Published: May 2018

Pathological conditions affecting skeletal muscle function may lead to irreversible volumetric muscle loss (VML). Therapeutic approaches involving acellular matrices represent an emerging and promising strategy to promote regeneration of skeletal muscle following injury. Here we investigated the ability of three different decellularised skeletal muscle scaffolds to support muscle regeneration in a xenogeneic immune-competent model of VML, in which the EDL muscle was surgically resected. All implanted acellular matrices, used to replace the resected muscles, were able to generate functional artificial muscles by promoting host myogenic cell migration and differentiation, as well as nervous fibres, vascular networks, and satellite cell (SC) homing. However, acellular tissue mainly composed of extracellular matrix (ECM) allowed better myofibre three-dimensional (3D) organization and the restoration of SC pool, when compared to scaffolds which also preserved muscular cytoskeletal structures. Finally, we showed that fibroblasts are indispensable to promote efficient migration and myogenesis by muscle stem cells across the scaffolds in vitro. This data strongly support the use of xenogeneic acellular muscles as device to treat VML conditions in absence of donor cell implementation, as well as in vitro model for studying cell interplay during myogenesis.
Predators and nutrient availability favor protozoa-resisting bacteria in aquatic systems
Authors: Andersson A. , Ahlinder J. , Mathisen P. , Hägglund M. , Bäckman S. , Nilsson E. , Sjödin A. , Thelaus J.
Published: May 2018

The long co-existence of bacteria and protozoa has led to the development of bacterial protozoa resistance strategies, which are suggested to serve as drivers for the evolution of pathogenic bacteria. However, the ecological mechanisms underpinning selection for protozoa-resistance in aquatic bacteria are poorly known. To assess the role of nutrient availability and predation-pressure on selection for protozoa-resisting bacteria (PRB), an enrichment-dilution experiment was designed using laboratory microcosms containing natural lake water. PRB was monitored by screening 16S rRNA amplicon sequence data for reads assigned to bacteria that previously has been shown to resist degradation by amoebae. To estimate the effects of the microbial food web dynamics (microscopy of; heterotrophic bacteria, phytoplankton, protozoa and rotifers) and physicochemical variables on the PRB abundance in the study system, a joint species distribution modelling approach was used. The predation-pressure (ratio between predator and bacterial biomass) had a positive effect on the abundance of the PRB genusMycobacterium, while perturbation (enrichment and dilution) favored the PRB genusPseudomonasthat dominated the bacterial community in the disturbed systems. Our results show that PRB with different ecological strategies can be expected in water of high and intermediate nutrient levels and after major disturbances of an aquatic system.
3D-printed components for quantum devices
Authors: Saint R. , Evans W. , Zhou Y. , Barrett T. , Fromhold T. M. , Saleh E. , Maskery I. , Tuck C. , Wildman R. , Oručević F. , Krüger P.
Published: May 2018

Recent advances in the preparation, control and measurement of atomic gases have led to new insights into the quantum world and unprecedented metrological sensitivities, e.g. in measuring gravitational forces and magnetic fields. The full potential of applying such capabilities to areas as diverse as biomedical imaging, non-invasive underground mapping, and GPS-free navigation can only be realised with the scalable production of efficient, robust and portable devices. We introduce additive manufacturing as a production technique of quantum device components with unrivalled design freedom and rapid prototyping. This provides a step change in efficiency, compactness and facilitates systems integration. As a demonstrator we present an ultrahigh vacuum compatible ultracold atom source dissipating less than ten milliwatts of electrical power during field generation to produce large samples of cold rubidium gases. This disruptive technology opens the door to drastically improved integrated structures, which will further reduce size and assembly complexity in scalable series manufacture of bespoke portable quantum devices.
A cryptic Gondwana-forming orogen located in Antarctica
Authors: Daczko Nathan R. , Halpin Jacqueline A. , Fitzsimons Ian C. W. , Whittaker Joanne M.
Published: May 2018

The most poorly exposed and least understood Gondwana-forming orogen lies largely hidden beneath ice in East Antarctica. Called the Kuunga orogen, its interpolation between scattered outcrops is speculative with differing and often contradictory trends proposed, and no consensus on the location of any sutures. While some discount a suture altogether, paleomagnetic data from Indo-Antarctica and Australo-Antarctica do require 3000–5000 km relative displacement during Ediacaran-Cambrian Gondwana amalgamation, suggesting that the Kuunga orogen sutured provinces of broadly Indian versus Australian affinity. Here we use compiled data from detrital zircons offshore of East Antarctica that fingerprint two coastal subglacial basement provinces between 60 and 130°E, one of Indian affinity with dominant ca. 980–900 Ma ages (Indo-Antarctica) and one of Australian affinity with dominant ca. 1190–1140 and ca. 1560 Ma ages (Australo-Antarctica). We combine this offshore compilation with existing and new onshore U-Pb geochronology and previous geophysical interpretations to delimit the Indo-Australo-Antarctic boundary at a prominent geophysical lineament which intersects the coast east of Mirny at ~94°E.
Further evidence for “gain-of-function” mechanism of DFNA5 related hearing loss
Authors: Wang Hongyang , Guan Jing , Guan Liping , Yang Ju , Wu Kaiwen , Lin Qiongfen , Xiong Wenping , Lan Lan , Zhao Cui , Xie Linyi , Yu Lan , Dan Bing  , Zhao Lidong , Wang Dayong , Wang Qiuju
Published: May 2018

To report two DFNA5 pathogenic splice-site variations and a novel benign frameshift variation to further support the gain-of-function mechanism of DFNA5 related hearing impairment, targeted genes capture and next generation sequencing were performed on selected members from Family 1007208, 1007081 and a sporadic case with sensorineural hearing loss. Reverse transcriptase polymerase chain reaction was conducted on the proband from Family 1007208 to test how the splice-site variation affects the transcription in RNA level. A novel heterozygous splice-site variation c.991-3 C > A in DFNA5 was found in Family 1007208; a known hotspot heterozygous splice-site variation c.991-15_991_13delTTC was identified in Family 1007081. Both the splice-site variations were segregated with the late onset hearing loss phenotype, leading to the skipping of exon 8 at RNA level. In addition, a novel DFNA5 frameshift variation c.116_119delAAAA was found in the sporadic case, but was not segregated with the hearing impairment phenotype. In conclusion, we identified one novel and one known pathogenic DFNA5 splice-site variation in two Chinese Families, as well as a novel DFNA5 frameshift variation c.116_119delAAAA in a sporadic case, which does not the cause for the hearing loss case. Both the two pathogenic splice-site variations and the nonpathogenic frameshift variation provide further support for the specific gain-of-function mechanism of DFNA5 related hearing loss.
Vibrio cholerae accessory colonisation factor AcfC: a chemotactic protein with a role in hyperinfectivity
Authors: Valiente Esmeralda , Davies Cadi , Mills Dominic C. , Getino Maria , Ritchie Jennifer M. , Wren Brendan W.
Published: May 2018

Vibrio cholerae O1 El Tor is an aquatic Gram-negative bacterium responsible for the current seventh pandemic of the diarrheal disease, cholera. A previous whole-genome analysis on V. cholerae O1 El Tor strains from the 2010 epidemic in Pakistan showed that all strains contained the V. cholerae pathogenicity island-1 and the accessory colonisation gene acfC (VC_0841). Here we show that acfC possess an open reading frame of 770 bp encoding a protein with a predicted size of 28 kDa, which shares high amino acid similarity with two adhesion proteins found in other enteropathogens, including Paa in serotype O45 porcine enteropathogenic Escherichia coli and PEB3 in Campylobacter jejuni. Using a defined acfC deletion mutant, we studied the specific role of AcfC in V. cholerae O1 El Tor environmental survival, colonisation and virulence in two infection model systems (Galleria mellonella and infant rabbits). Our results indicate that AcfC might be a periplasmic sulfate-binding protein that affects chemotaxis towards mucin and bacterial infectivity in the infant rabbit model of cholera. Overall, our findings suggest that AcfC contributes to the chemotactic response of WT V. cholerae and plays an important role in defining the overall distribution of the organism within the intestine.