bluuebunny/crossref_metadata_2025 huggingface dataset:
Does responsiveness to arbuscular mycorrhizal fungi depend on plant invasive status?
Authors: Reinhart Kurt O. , Lekberg Ylva , Klironomos John , Maherali Hafiz
Published: July 2017

Differences in the direction and degree to which invasive alien and native plants are influenced by mycorrhizal associations could indicate a general mechanism of plant invasion, but whether or not such differences exist is unclear. Here, we tested whether mycorrhizal responsiveness varies by plant invasive status while controlling for phylogenetic relatedness among plants with two large grassland datasets. Mycorrhizal responsiveness was measured for 68 taxa from the Northern Plains, and data for 95 taxa from the Central Plains were included. Nineteen percent of taxa from the Northern Plains had greater total biomass with mycorrhizas while 61% of taxa from the Central Plains responded positively. For the Northern Plains taxa, measurable effects often depended on the response variable (i.e., total biomass, shoot biomass, and root mass ratio) suggesting varied resource allocation strategies when roots are colonized by arbuscular mycorrhizal fungi. In both datasets, invasive status was nonrandomly distributed on the phylogeny. Invasive taxa were mainly from two clades, that is, Poaceae and Asteraceae families. In contrast, mycorrhizal responsiveness was randomly distributed over the phylogeny for taxa from the Northern Plains, but nonrandomly distributed for taxa from the Central Plains. After controlling for phylogenetic similarity, we found no evidence that invasive taxa responded differently to mycorrhizas than other taxa. Although it is possible that mycorrhizal responsiveness contributes to invasiveness in particular species, we find no evidence that invasiveness in general is associated with the degree of mycorrhizal responsiveness. However, mycorrhizal responsiveness among species grown under common conditions was highly variable, and more work is needed to determine the causes of this variation.
Seaside Sparrows reveal contrasting food web responses to large‐scale stressors in coastal Louisiana saltmarshes
Authors: Olin Jill A. , Bergeon Burns Christine M. , Woltmann Stefan , Taylor Sabrina S. , Stouffer Philip C. , Bam Wokil , Hooper‐Bui Linda , Turner R. Eugene
Published: July 2017

Large‐scale ecosystem disturbances can alter the flow of energy through food webs, but such processes are not well defined for Gulf of Mexico saltmarsh ecosystems vulnerable to multiple interacting stressors. The 2010 Deepwater Horizon (DWH) oil spill significantly affected the composition of terrestrial saltmarsh communities in Louisiana, and thus had the potential to alter energy pathways through terrestrial and aquatic food webs, with direct consequences for higher trophic‐level species restricted to these habitats. The Seaside Sparrow (Ammodramus maritimus) is endemic to saltmarshes and relies completely on the habitat and resources they provide; thus, the sparrows can serve as indicators of ecological change in response to disturbances. We analyzed food web pathways for birds residing in oiled and unoiled saltmarshes for the four years following the oil spill by quantifying the bulk carbon and nitrogen stable isotopes and fatty acid profiles of liver tissues, in addition to primary producers (e.g., marsh grasses) and invertebrate consumers representing the major energy resources in these systems. The stable isotope values of primary producers and most invertebrate consumers did not differ between oiled and unoiled sites, suggesting that the energy pathways within the food web were stable in spite of observed declines in these populations following the spill. The tracer profiles of the Seaside Sparrows confirmed that there was a nominal effect of oil on resource use or trophic position (TP). However, we detected significant inter‐annual variation in resource use by these birds; the sparrows occupied a lower TP and exhibited greater assimilation of resources derived from benthic–aquatic relative to terrestrial pathways in 2013 compared to other years. This distinction is likely attributable to the effects of Hurricane Isaac in 2012, whose significant storm surge extensively inundated the saltmarsh landscape. Despite widespread concern for the saltmarsh ecosystem after the DWH event, the significant effects noted at the population level translated into only subtle differences to the flow of energy through this food web. These results demonstrate varying responses to different degrees of landscape‐level disturbance, such as oil and hurricanes, and establish the need to better understand food web dynamics in these saltmarsh ecosystems.
Origins of Dendrite Formation in Sodium–Oxygen Batteries and Possible Countermeasures
Authors: Medenbach Lukas , Bender Conrad L. , Haas Ronja , Mogwitz Boris , Pompe Constantin , Adelhelm Philipp , Schröder Daniel , Janek Jürgen
Published: July 2017

One limiting phenomenon for the cycle life of metal–oxygen batteries is the growth of dendrites during metal plating (cell charging). For the relatively new sodium–oxygen cell, this subject has been scarcely investigated, until now. Therefore, dendrite formation is systematically investigated herein, with the aim of gaining a more detailed understanding of the underlying mechanisms and relevant control parameters. Electrochemical impedance spectroscopy, cycling experiments, and optical characterization techniques are applied in situ and ex situ; sodium dendrite growth is directly visualized, for the first time, by means of a tubular glass cell. The growth of instable surface morphologies is discussed from a theoretical perspective to comprehend the experimentally observed dendrite growth. Furthermore, countermeasures against issues with dendrites are discussed, with the aim of increasing the cycle life of sodium–oxygen batteries.
Functional variants in HCN4 and CACNA1H may contribute to genetic generalized epilepsy
Authors: Becker Felicitas , Reid Christopher A. , Hallmann Kerstin , Tae Han‐Shen , Phillips A. Marie , Teodorescu Georgeta , Weber Yvonne G. , Kleefuss‐Lie Ailing , Elger Christian , Perez‐Reyes Edward , Petrou Steven , Kunz Wolfram S. , Lerche Holger , Maljevic Snezana
Published: July 2017

Objective

Genetic generalized epilepsy (GGE) encompasses seizure disorders characterized by spike‐and‐wave discharges (SWD) originating within thalamo‐cortical circuits. Hyperpolarization‐activated (HCN) and T‐type Ca2+ channels are key modulators of rhythmic activity in these brain regions. Here, we screened HCN4 and CACNA1H genes for potentially contributory variants and provide their functional analysis.

Methods

Targeted gene sequencing was performed in 20 unrelated familial cases with different subtypes of GGE, and the results confirmed in 230 ethnically matching controls. Selected variants in CACNA1H and HCN4 were functionally assessed in tsA201 cells and Xenopus laevis oocytes, respectively.

Results

We discovered a novel CACNA1H (p.G1158S) variant in two affected members of a single family. One of them also carried an HCN4 (p.P1117L) variant inherited from the unaffected mother. In a separate family, an HCN4 variant (p.E153G) was identified in one of several affected members. Voltage‐clamp analysis of CACNA1H (p.G1158S) revealed a small but significant gain‐of‐function, including increased current density and a depolarizing shift of steady‐state inactivation. HCN4 p.P1117L and p.G153E both caused a hyperpolarizing shift in activation and reduced current amplitudes, resulting in a loss‐of‐function.

Significance

Our results are consistent with a model suggesting cumulative contributions of subtle functional variations in ion channels to seizure susceptibility and GGE.
„Bitte einfach nur: Wüstenforscher“
Authors: Heimlich Rüdiger
Published: July 2017

Ob in Filmdokus, Ausstellungen, Vorträgen oder Artikeln: Seit Jahrzehnten wirbt der Kölner Geologe und Klimaforscher Stefan Kröpelin weltweit für die Geschichte, die Landschaften und die Menschen der Sahara. Jetzt würdigen DFG und Stifterverband mit dem „Communicator‐Preis“ den Feldforscher, der in mehrfacher Hinsicht auch ein „Botschafter der Wissenschaft“ ist.
Advocacy, communication, and partnerships: Mobilizing for effective, widespread cervical cancer prevention
Authors: Wittet Scott , Aylward Jenny , Cowal Sally , Drope Jacqui , Franca Etienne , Goltz Sarah , Kuo Taona , Larson Heidi , Luciani Silvana , Mugisha Emmanuel , Schocken Celina , Torode Julie
Published: July 2017

Both human papillomavirus (HPV) vaccination and screening/treatment are relatively simple and inexpensive to implement at all resource levels, and cervical cancer screening has been acknowledged as a “best buy” by the WHO. However, coverage with these interventions is low where they are needed most. Failure to launch or expand cervical cancer prevention programs is by and large due to the absence of dedicated funding, along with a lack of recognition of the urgent need to update policies that can hinder access to services. Clear and sustained communication, robust advocacy, and strategic partnerships are needed to inspire national governments and international bodies to action, including identifying and allocating sustainable program resources. There is significant momentum for expanding coverage of HPV vaccination and screening/preventive treatment in low‐resource settings as evidenced by new global partnerships espousing this goal, and the participation of groups that previously had not focused on this critical health issue.
Authentic Leadership and Transformational Leadership: An Incremental Approach
Authors: Rodriguez Richard A. , Green Mark T. , Sun Yu , Baggerly‐Hinojosa Barbara
Published: July 2017

Authentic leadership and transformational leadership are significant predictors of job satisfaction. However, controversy abounds as authentic leadership faces intense scrutiny. Using data from a heterogeneous sample of 323 working adults, an exploratory factor analysis revealed 81% of the variance in nine first‐order factors to be explained by one component. Findings from a confirmatory factor analysis appeared to show a two‐factor model as a better fit than a one‐factor model, yet neither model met a generally accepted threshold for RMSEA. Multiple regression analysis generated modest levels of incremental validity for authentic leadership, above and beyond the effects of transformational leadership, in the prediction of intrinsic, extrinsic, and general job satisfaction. Additional multiple regression analyses involving first‐order factors revealed morals/ethics as a significant predictor of intrinsic job satisfaction, above and beyond the effects of individual consideration and inspirational motivation. Self‐awareness and balanced processing were found to be significant predictors of extrinsic job satisfaction, above and beyond the effects of individual consideration, attributed idealized influence, and intellectual stimulation. Lastly, balanced processing was found to be a significant predictor of general job satisfaction, above and beyond the effects of individual consideration, inspirational motivation, and intellectual stimulation. Further assessments regarding the unique nature of authentic leadership are recommended.
Synthesis, Characterization, and Properties of Poly(aryl)phosphinoboranes Formed via Iron‐Catalyzed Dehydropolymerization
Authors: Turner Joshua R. , Resendiz‐Lara Diego A. , Jurca Titel , Schäfer André , Vance James R. , Beckett Laura , Whittell George R. , Musgrave Rebecca A. , Sparkes Hazel A. , Manners Ian
Published: July 2017

The dehydropolymerization of the primary phosphine–boranes, RPH2•BH3 (1a–f) (R = 3,4‐(OCH2O)C6H3 (a), Ph (b), p‐(CF3O)C6H4 (c), 3,5‐(CF3)2C6H3 (d), 2,4,6‐(CH3)3C6H2 (e), 2,4,6‐tBu3C6H2 (f)) is explored using the precatalyst [CpFe(CO)2OTf] (I) (OTf = OS(O)2CF3), based on the earth abundant element Fe. Formation of polyphosphinoboranes [RPH‐BH2]n (2a–e) is confirmed by multinuclear NMR spectroscopy, but no conversion of 1f to 2f is detected. Analysis by electrospray ionization mass spectrometry confirms the presence of the anticipated polymer repeat units for 2a–e. Gel permeation chromatography (GPC) confirms the polymeric nature of 2a–e and indicates number‐average molecular weights (Mn) of 12 000–209 000 Da and polydispersity indices between 1.14 and 2.17. By contrast, thermal dehydropolymerization of 1a–e in the absence of added precatalyst leads to formation of oligomeric material. Interestingly, polyphosphinoboranes 2c and 2d display GPC behavior typical of polyelectrolytes, with a hydrodynamic radius dependent on concentration. The thermal transition behavior, thermal stability, and surface properties of thin films are also studied.
In Situ Crosslinking of Highly Porous Chitosan Scaffolds for Bone Regeneration: Production Parameters and In Vitro Characterization
Authors: Kruppke Benjamin , Farack Jana , Sommer Freya , Weil Simy , Aflalo Eliahu David , Wiesmann Hans‐Peter , Sagi Amir , Hanke Thomas
Published: July 2017

Various methods of chitosan scaffold production are reported in the literature so far. Here, in situ crosslinking with glutaraldehyde is reported for the first time. It combines pore formation and chitosan crosslinking in a single step. This combination allows incorporation of fragile molecules into 3D porous chitosan scaffolds produced by simple and gentle lyophilization. In this study, parameters of in situ crosslinking of porous chitosan scaffold formation as well as their effect on degradation and bioactivity of the scaffolds are examined. The scaffolds are characterized in the context of their prospective application as bone substitute material. The addition of calcium phosphate phases (hydroxyapatite, brushite) to the macroporous chitosan scaffolds allows manipulation of the bioactivity that is investigated by incubation in simulated body fluid (SBF). The bioactivity is significantly influenced by the modus of changing the fluid (static, daily‐, and twice‐a‐week change). Scaffolds are morphologically characterized by means of scanning electron microscopy, and the mechanical stability is tested after incubation in SBF and phosphate‐buffered saline.
Ultrastrong and Tough Supramolecular Hydrogels from Multiurea Linkage Segmented Copolymers with Tractable Processablity and Recyclability
Authors: Yang Nannan , Yang Huili , Shao Zengwu , Guo Mingyu
Published: July 2017

Strong and tough synthetic hydrogels have received ever‐increasing interests due to their potential applications as load‐bearing structural materials. However, strong, tough, and recyclable hydrogels in different forms that can be generated by different methods according to various practical applications still remain an intrinsic bottleneck. A simple one‐pot synthesis of multiurea linkage segmented linear copolymers with easy recyclability, hybridization, and processability, including compression molding, solution casting, and spinning methods, to yield ultrastrong and tough hydrogel films or stretchable hydrogel fibers with diameters ranged from macro‐, micro‐, to nanoscale, is reported here.
Bioaccessibility, bioavailability, and anti‐inflammatory effects of anthocyanins from purple root vegetables using mono‐ and co‐culture cell models
Authors: Zhang Hua , Hassan Yousef I. , Renaud Justin , Liu Ronghua , Yang Cheng , Sun Yong , Tsao Rong
Published: July 2017

Scope

Immune‐inflammatory signaling and metabolic effects are the main pillars for bioactivity of anthocyanins derived from highly pigmented root vegetables. This study aims to assess the bioaccessibility and bioavailability of purple carrot and potato derived anthocyanins and the molecular mechanisms of their ability to ameliorate cellular inflammation in a mono‐ and co‐culture cell models.

Methods and results

An in vitro gastrointestinal model was used and demonstrated bioaccessibility of 44.62 and 71.8% for anthocyanins of purple carrot and potato, respectively. These accessible anthocyanins significantly inhibited cellular inflammation in Caco‐2 cells. Intact cyanidinglycoside or petunidinglycoside (respectively from carrots and potatoes) were transported across a transmembrane cell model and detected by LC‐MS/MS. Computational docking and glucose uptake analyses suggested uptake of anthocyanins was mediated by hexose transporters. Subsequent experiment using an inflamed Caco‐2 BBe1/THP‐1 co‐culture cell model showed these transported anthocyanins inhibited IL‐8 and TNF‐α secretion,and expression of pro‐inflammatory cytokines by blocking NF‐κB, and MAPK mediated inflammatory cellular signaling cascades, but with varying degrees due to structural features.

Conclusion

Anthocyanins from purple carrots and potatoes possess a promising anti‐inflammatory effect in model gut system. They can be absorbed and act differently but are in general beneficial for inflammation‐mediated diseases.
Carpal tunnel syndrome in inherited neuropathies: A retrospective survey
Authors: Panosyan Francis B. , Kirk Callyn A. , Marking Devon , Reilly Mary M. , Scherer Steven S. , Shy Michael E. , Herrmann David N.
Published: July 2017

Introduction

This study evaluates carpal tunnel syndrome (CTS) symptom severity, functional status, and outcome of CTS therapies in patients with inherited neuropathies.

Methods

Validated questionnaires were used to compare symptom severity and functional status in patients with and without a diagnosis of CTS and a diagnosis of an inherited neuropathy.

Results

309 patients with inherited neuropathies participated in this study. The CTS symptom severity score (SSS) was found to be the most useful tool in assessing CTS severity in patients with inherited neuropathy. Splint therapy and surgery were associated with significant improvement in carpal tunnel symptoms as measured through the SSS.

Discussion

This study provides insight into the assessment of CTS symptom severity and patient‐reported outcomes to CTS therapy in individuals with inherited neuropathies. The SSS appears useful for evaluation of CTS symptoms and patient‐reported outcomes following CTS interventions in individuals with inherited neuropathies. Muscle Nerve 57: 388–394, 2018
Rigor of non‐dairy galactose restriction in early childhood, measured by retrospective survey, does not associate with severity of five long‐term outcomes quantified in 231 children and adults with classic galactosemia
Authors: Frederick Allison B. , Cutler David J. , Fridovich‐Keil Judith L.
Published: July 2017

One of many vexing decisions faced by parents of an infant with classic galactosemia (CG) is how carefully to restrict non‐dairy galactose from their growing child's diet. Until recently, many experts recommended vigorous lifelong dietary restriction of milk and all high‐galactose dairy products as well as some non‐dairy sources of galactose such as legumes and specific fruits and vegetables. Recently, experts have begun to relax their recommendations. The new recommendations, that restrict only high galactose dairy products, were made in the face of uncertainty, however, because no sufficiently powered study had been reported testing for possible association between rigor of non‐dairy galactose restriction and severity of long‐term outcomes in CG. Here we describe the largest study of diet and outcomes in CG reported to date, conducted using information gathered from 231 patients with CG and 71 unaffected sibling controls. We compared rigor of dietary galactose restriction, measured using a 4‐point scale by a retrospective parent‐response survey, with outcomes including growth, adaptive behaviors, receipt of speech therapy, receipt of special educational services, and for girls and women, a plasma marker of ovarian function (AMH). Our results confirmed the expected differences between patients and controls, but among patients showed no significant association between rigor of non‐dairy galactose restriction in early childhood and any of the outcomes quantified. Indeed, some weak associations were seen suggesting that rigorous restriction of non‐dairy galactose may be deleterious rather than beneficial. Despite limitations, these findings support the ongoing trend toward diet liberalization with regard to non‐dairy sources of galactose for children and adults with classic galactosemia.
C-Curves for Lengthening of Widmanstätten and Bainitic Ferrite
Authors: Yin Jiaqing , Leach Lindsay , Hillert Mats , Borgenstam Annika
Published: July 2017

Widmanstätten ferrite and bainitic ferrite are both acicular and their lengthening rate in binary Fe-C alloys and low-alloyed steels under isothermal conditions is studied by searching the literature and through new measurements. As a function of temperature, the lengthening rate can be represented by a common curve for both kinds of acicular ferrite in contrast to the separate C-curves often presented in time-temperature-transformation (TTT) diagrams. The curves for Fe-C alloys with low carbon content show no obvious decrease in rate at low temperatures down to 623 K (350 °C). For alloys with higher carbon content, the expected decrease of rate as a function of temperature below a nose was observed. An attempt to explain the absence of a nose for low carbon contents by an increasing deviation from local equilibrium at high growth rates is presented. This explanation is based on a simple kinetic model, which predicts that the growth rates for Fe-C alloys with less than 0.3 mass pct carbon are high enough at low temperatures to make the carbon pileup, in front of the advancing tip of a ferrite plate, shrink below atomic dimensions, starting at about 600 K (323 °C).
Early life stress explains reduced positive memory biases in remitted depression
Authors: Gethin J.A. , Lythe K.E. , Workman C.I. , Mayes A. , Moll J. , Zahn R.
Published: July 2017

Background:

There is contradictory evidence regarding negative memory biases in major depressive disorder (MDD) and whether these persist into remission, which would suggest their role as vulnerability traits rather than correlates of mood state. Early life stress (ELS), common in patients with psychiatric disorders, has independently been associated with memory biases, and confounds MDD versus control group comparisons. Furthermore, in most studies negative biases could have resulted from executive impairments rather than memory difficulties per se.

Methods:

To investigate whether memory biases are relevant to MDD vulnerability and how they are influenced by ELS, we developed an associative recognition memory task for temporo-spatial contexts of social actions with low executive demands, which were matched across conditions (self-blame, other-blame, self-praise, other-praise). We included fifty-three medication-free remitted MDD (25 with ELS, 28 without) and 24 healthy control (HC) participants without ELS.

Results:

Only MDD patients with ELS showed a reduced bias (accuracy/speed ratio) towards memory for positive vs. negative materials when compared with MDD without ELS and with HC participants; attenuated positive biases correlated with number of past major depressive episodes, but not current symptoms. There were no biases towards self-blaming or self-praising memories.

Conclusions:

This demonstrates that reduced positive biases in associative memory were specific to MDD patients with ELS rather than a general feature of MDD, and were associated with lifetime recurrence risk which may reflect a scarring effect. If replicated, our results would call for stratifying MDD patients by history of ELS when assessing and treating emotional memories.
Price Effects of Establishing a New Sub-AVA within Oregon's Willamette Valley AVA
Authors: Gokcekus Omer , Finnegan Clare M.
Published: July 2017

The creation of new sub-divisions within Oregon's Willamette Valley American Viticultural Area (AVA) may indicate a desire on the part of well-established wineries to “split” or separate their social groupings from those with lesser qualifications. Once their social clusters have been differentiated, we theorize that these wineries would be able to capitalize on their newly developed distinctiveness and collect larger regional reputation premiums. Based on 2,221 Wine Spectator–rated pinot noirs from between 1984 and 2008, regression analyses demonstrate that regional reputation premiums have significantly increased with the creation of sub-AVAs and that the price-quality ratio gap between sub-AVAs and the rest of Willamette has widened. (JEL Classifications: D22, Q12, L14)
The ‘ph’ of English orthography; a digraph or a sequence of separate phonemes?
Authors: Achiri-Taboh Blasius
Published: July 2017

The aim of this short article is to offer a belated defense of L. M. Boyd (author of a daily, nationally syndicated column ‘Trivia’ in numerous newspapers throughout the USA) against a critique published in English Today over a decade ago by Alan S. Kaye (2006), and present arguments in support of Boyd's beleaguered claim. Kaye (2006: 54) writes:

I do not mean to be picking on Mr. Boyd, but considering his track record, perhaps the time has come for his quitting pontificating on matters of English grammar, pronunciation, and the history of the language.
‘Mod Movement in Quality Street Clothes’: British Popular Music and Pantomime, 1955–75
Authors: Mitchell Gillian A. M.
Published: July 2017

From the late 1950s onwards, young rock ‘n’ roll musicians and popular singers were introduced into commercial Christmas pantomime productions. While this practice, which constituted an extension of their involvement in the broader sphere of variety theatre, has been previously noted, it is seldom accorded much sustained attention. In this article Gillian Mitchell explores the impact which such performers made upon pantomime, while observing the ways in which involvement in pantomime productions affected their careers and aspirations. ‘Pop stars’ brought much-needed revenue to struggling theatres, and, while their presence onstage alongside experienced pantomime performers sometimes attracted criticism, they also contributed in many ways to a reinvigoration of the medium, whether by offering fresh scope for topical gags, or by giving ambitious producers the chance to more more experimental types of production. The article also questions the notion that, by the late 1960s, pantomime had become a ‘last refuge’ for those popular musicians who were apparently unable to maintain a foothold in the increasingly ‘serious’ world of rock music. Gillian A.M. Mitchell is a Lecturer in Modern History at the University of St Andrews. This article forms part of a larger project which explores adult reactions to popular music and inter-generational relations in Britain from the 1950s to the 1970s.
Art and Insurgency in Urgent Times
Authors: ALCURE ADRIANA SCHNEIDER
Published: July 2017

Brazil's constitutional crisis that culminated in the impeachment of President Dilma Rousseff in 2016 triggered a series of popular protests throughout the country. Starting with a brief analysis of the current political situation, this text identifies the characteristics, tools and forms of these political protests, drawing connections between them and debates in the arts.
Successful ageing, depression and resilience research; a call for a priori approaches to investigations of resilience
Authors: Huisman M. , Klokgieters S. S. , Beekman A. T. F.
Published: July 2017

Given the multitude of risk factors for depression in modern society and given the negative consequences of depressive problems for successful ageing, investigating resilience in relation to depression may help identifying entry points for reducing the burden of morbidity. Research on resilience begins with the realisation that individuals may demonstrate good physical or psychological functioning despite being exposed to risk experiences that can have serious negative impact on functioning. Interest in investigating resilience within ageing research has been increasing. Among the approaches toward investigating resilience are so-called a priori approaches, where criteria for inferring resilience are established a priori. In this editorial, we highlight some of the advantages of taking a priori approaches to the study of resilience and we touch on the implications for a priori approaches for the topic of resilience and depression. We argue that depression should take a prominent role in resilience research, because depression is strongly associated with opportunities for successful ageing.
Epigallocatechin-3-gallate enhances ER stress-induced cancer cell apoptosis by directly targeting PARP16 activity
Authors: Wang Juanjuan , Zhu Chenggang , Song Dan , Xia Ruiqi , Yu Wenbo , Dang Yongjun , Fei Yiyan , Yu Long , Wu Jiaxue
Published: July 2017

Poly(ADP-ribose) polymerases (PARPs) are ADP-ribosylating enzymes and play important roles in a variety of cellular processes. Most small-molecule PARP inhibitors developed to date have been against PARP1, a poly-ADP-ribose transferase, and suffer from poor selectivity. PARP16, a mono-ADP-ribose transferase, has recently emerged as a potential therapeutic target, but its inhibitor development has trailed behind. Here we newly characterized epigallocatechin-3-gallate (EGCG) as a potential inhibitor of PARP16. We found that EGCG was associated with PARP16 and dramatically inhibited its activity in vitro. Moreover, EGCG suppressed the ER stress-induced phosphorylation of PERK and the transcription of unfolded protein response-related genes, leading to dramatically increase of cancer cells apoptosis under ER stress conditions, which was dependent on PARP16. These findings newly characterized EGCG as a potential inhibitor of PARP16, which can enhance the ER stress-induced cancer cell apoptosis, suggesting that a combination of EGCG and ER stress-induced agents might represent a novel approach for cancer therapy or chemoprevention.
Neoadjuvant chemotherapy affects molecular classification of colorectal tumors
Authors: Trumpi K , Ubink I , Trinh A , Djafarihamedani M , Jongen J M , Govaert K M , Elias S G , van Hooff S R , Medema J P , Lacle M M , Vermeulen L , Borel Rinkes I H M , Kranenburg O
Published: July 2017

The recent discovery of ‘molecular subtypes’ in human primary colorectal cancer has revealed correlations between subtype, propensity to metastasize and response to therapy. It is currently not known whether the molecular tumor subtype is maintained after distant spread. If this is the case, molecular subtyping of the primary tumor could guide subtype-targeted therapy of metastatic disease. In this study, we classified paired samples of primary colorectal carcinomas and their corresponding liver metastases (n=129) as epithelial-like or mesenchymal-like, using a recently developed immunohistochemistry-based classification tool. We observed considerable discordance (45%) in the classification of primary tumors and their liver metastases. Discordant classification was significantly associated with the use of neoadjuvant chemotherapy. Furthermore, gene expression analysis of chemotherapy-exposed versus chemotherapy naive liver metastases revealed expression of a mesenchymal program in pre-treated tumors. To explore whether chemotherapy could cause gene expression changes influencing molecular subtyping, we exposed patient-derived colonospheres to six short cycles of 5-fluorouracil. Gene expression profiling and signature enrichment analysis subsequently revealed that the expression of signatures identifying mesenchymal-like tumors was strongly increased in chemotherapy-exposed tumor cultures. Unsupervised clustering of large cohorts of human colon tumors with the chemotherapy-induced gene expression program identified a poor prognosis mesenchymal-like subgroup. We conclude that neoadjuvant chemotherapy induces a mesenchymal phenotype in residual tumor cells and that this may influence the molecular classification of colorectal tumors.
Role of insulin receptor substrates in the progression of hepatocellular carcinoma
Authors: Sakurai Yoshitaka , Kubota Naoto , Takamoto Iseki , Obata Atsushi , Iwamoto Masahiko , Hayashi Takanori , Aihara Masakazu , Kubota Tetsuya , Nishihara Hiroshi , Kadowaki Takashi
Published: July 2017

Several cellular signaling pathways, including insulin/IGF signaling, are known to be activated in hepatocellular carcinoma (HCC). Here, we investigated the roles of insulin receptor substrate (Irs) 1 and Irs2, both of which are the major molecules to be responsible for transducing insulin/IGF signaling in the liver, in the development of HCC by inducing chemical carcinogenesis using diethylnitrosamine (DEN) in mice. The Irs1 mRNA and protein expressions were upregulated in the tumors, along with enhanced insulin signaling. Liver-specific Irs1-knockout (LIrs1KO) mice exhibited suppression of DEN-induced HCC development, accompanied by reduced cancer cell proliferative activity and reduced activation of Akt. Gene expression analyses revealed that the tumors in the DEN-treated LIrs1KO mice showed modest metabolic alterations during hepatocarcinogenesis as well as decreased inflammation and invasion potentials. On the other hand, liver-specific Irs2-knockout (LIrs2KO) mice showed a similar pattern of HCC development to the DEN-treated control wild-type mice. Based on the knowledge that Wnt/β-catenin signaling is activated in HCC, we focused on Wnt/β-catenin signaling and demonstrated that Irs1 expression was induced by Wnt3a stimulation in the primary hepatocytes, associated with insulin-stimulated Akt activation. These data suggest that upregulated Irs1 by Wnt/β-catenin signaling plays a crucial role in the progression of HCC.
Neural correlates of altered feedback learning in women recovered from anorexia nervosa
Authors: Ritschel Franziska , Geisler Daniel , King Joseph A. , Bernardoni Fabio , Seidel Maria , Boehm Ilka , Vettermann Richard , Biemann Ronald , Roessner Veit , Smolka Michael N. , Ehrlich Stefan
Published: July 2017

Anorexia nervosa (AN) is associated with exaggerated self-control and altered reward-based decision making, but the underlying neural mechanisms are poorly understood. Consistent with the notion of excessive cognitive control, we recently found increased dorsal anterior cingulate cortex (dACC) activation in acutely ill patients (acAN) on lose-shift trials in a probabilistic reversal learning (PRL) task. However, undernutrition may modulate brain function. In attempt to disentangle trait from state factors, the current fMRI study investigated cognitive control in recovered patients (recAN). Thirty-one recAN and 31 healthy controls (HC) completed a PRL task during fMRI. Based on previous findings, we focused on hemodynamic responses during lose-shift behaviour and conducted supplementary functional connectivity analysis. RecAN showed elevated lose-shift behaviour relative to HC. On the neural level, recAN showed normal dACC responses, but increased activation in fronto-parietal control regions. A trend for increased coupling between frontal and parietal regions of interest was also evident in recAN. The current findings in recAN differ from those in our previous study in acAN. While aberrant dACC response to negative feedback may be a correlate of the underweight state in acAN, impaired behavioural adaptation and elevated activation of cognitive control regions in recAN is suggestive of altered neural efficiency.
Plant recording across two centuries reveals dramatic changes in species diversity of a Mediterranean archipelago
Authors: Chiarucci Alessandro , Fattorini Simone , Foggi Bruno , Landi Sara , Lazzaro Lorenzo , Podani János , Simberloff Daniel
Published: July 2017

Although islands are model systems for investigating assembly of biological communities, long-term changes in archipelago communities are not well understood because of the lack of reliable data. By using a vast amount of floristic data we assembled a dataset of the plant species occurring on 16 islands of the Tuscan Archipelago, Italy, across two periods, 1830–1950 and 1951–2015. We collected 10,892 occurrence records for 1,831 species. We found major changes in the island plant assemblages between the two periods, with native flora significantly decreasing (−10.7%) and alien flora doubling (+132.1%) in richness. The species–area relationships demonstrated the scale-dependence of the observed changes for native and alien species. The observed floristic changes were dependent on island area, with smaller islands displaying high variability in richness and compositional changes and larger islands having more stable species assemblages. The richness of species associated with open landscapes, that had been maintained for centuries by traditional practices, markedly reduced while the number of woody species, associated with afforestation processes and invasion by alien woody plants, significantly incresed. These results demonstrate the great power of floristic studies, often available in grey literature, for understanding long-term biotic changes in insular ecosystems.
Effects of Lipoic Acid on High-Fat Diet-Induced Alteration of Synaptic Plasticity and Brain Glucose Metabolism: A PET/CT and 13C-NMR Study
Authors: Liu Zhigang , Patil Ishan , Sancheti Harsh , Yin Fei , Cadenas Enrique
Published: July 2017

High-fat diet (HFD)-induced obesity is accompanied by insulin resistance and compromised brain synaptic plasticity through the impairment of insulin-sensitive pathways regulating neuronal survival, learning, and memory. Lipoic acid is known to modulate the redox status of the cell and has insulin mimetic effects. This study was aimed at determining the effects of dietary administration of lipoic acid on a HFD-induced obesity model in terms of (a) insulin signaling, (b) brain glucose uptake and neuronal- and astrocytic metabolism, and (c) synaptic plasticity. 3-Month old C57BL/6J mice were divided into 4 groups exposed to their respective treatments for 9 weeks: (1) normal diet, (2) normal diet plus lipoic acid, (3) HFD, and (4) HFD plus lipoic acid. HFD resulted in higher body weight, development of insulin resistance, lower brain glucose uptake and glucose transporters, alterations in glycolytic and acetate metabolism in neurons and astrocytes, and ultimately synaptic plasticity loss evident by a decreased long-term potentiation (LTP). Lipoic acid treatment in mice on HFD prevented several HFD-induced metabolic changes and preserved synaptic plasticity. The metabolic and physiological changes in HFD-fed mice, including insulin resistance, brain glucose uptake and metabolism, and synaptic function, could be preserved by the insulin-like effect of lipoic acid.
NEK1 kinase domain structure and its dynamic protein interactome after exposure to Cisplatin
Authors: Melo-Hanchuk Talita D. , Slepicka Priscila Ferreira , Meirelles Gabriela Vaz , Basei Fernanda Luisa , Lovato Diogo Ventura , Granato Daniela Campos , Pauletti Bianca Alves , Domingues Romenia Ramos , Leme Adriana Franco Paes , Pelegrini Alessandra Luiza , Lenz Guido , Knapp Stefan , Elkins Jonathan M. , Kobarg Jörg
Published: July 2017

NEK family kinases are serine/threonine kinases that have been functionally implicated in the regulation of the disjunction of the centrosome, the assembly of the mitotic spindle, the function of the primary cilium and the DNA damage response. NEK1 shows pleiotropic functions and has been found to be mutated in cancer cells, ciliopathies such as the polycystic kidney disease, as well as in the genetic diseases short-rib thoracic dysplasia, Mohr-syndrome and amyotrophic lateral sclerosis. NEK1 is essential for the ionizing radiation DNA damage response and priming of the ATR kinase and of Rad54 through phosphorylation. Here we report on the structure of the kinase domain of human NEK1 in its apo- and ATP-mimetic inhibitor bound forms. The inhibitor bound structure may allow the design of NEK specific chemo-sensitizing agents to act in conjunction with chemo- or radiation therapy of cancer cells. Furthermore, we characterized the dynamic protein interactome of NEK1 after DNA damage challenge with cisplatin. Our data suggest that NEK1 and its interaction partners trigger the DNA damage pathways responsible for correcting DNA crosslinks.
Decreased serum apolipoprotein A1 levels are associated with poor survival and systemic inflammatory response in colorectal cancer
Authors: Sirniö Päivi , Väyrynen Juha P. , Klintrup Kai , Mäkelä Jyrki , Mäkinen Markus J. , Karttunen Tuomo J. , Tuomisto Anne
Published: July 2017

Recent studies have reported of an association between high serum apolipoprotein A1 (APOA1) levels and favorable prognosis in several malignancies, while the significance of apolipoprotein B (APOB) in cancer is less well-known. In this study, we analyzed the correlation between serum APOA1 and APOB levels, and APOB/APOA1 ratio, and their associations with clinicopathologic parameters, the levels of twenty systemic inflammatory markers, and survival in 144 colorectal cancer (CRC) patients. We demonstrated that low serum APOA1 levels associated with advanced T-class and TNM-stage but low serum APOB levels did not significantly correlate with tumor characteristics. Serum APOA1 levels showed strong negative correlation with the markers of systemic inflammation including serum CRP and interleukin (IL)-8 levels and blood neutrophil count, whereas high serum APOB levels associated with high serum CCL2 levels. High APOA1 and APOB levels and low APOB/APOA1 ratio associated with improved cancer specific and overall survival. APOA1 had independent prognostic value in Cox regression analysis. In conclusion, low serum APOA1 levels are associated with advanced stage and systemic inflammation, while serum APOB does not significantly correlate with tumor stage. Serum APOA1 represents a promising additional prognostic parameter in CRC.
Molecular inter-kingdom interactions of endophytes isolated from Lychnophora ericoides
Authors: Caraballo-Rodríguez Andrés M. , Dorrestein Pieter C. , Pupo Monica T.
Published: July 2017

The importance of microbial natural products has been widely demonstrated in the search for new antibiotics. However, the functional role of microbial metabolites in nature remains to be deciphered. Several natural products are known to mediate microbial interactions through metabolic exchange. One approach to investigate metabolic exchange in the laboratory is through microbial interactions. Here, we describe the chemical study of selected endophytes isolated from the Brazilian medicinal plant Lychnophora ericoides by pairwise inter-kingdom interactions in order to correlate the impact of co-cultivation to their metabolic profiles. Combining mass spectrometry tools and NMR analyses, a total of 29 compounds were identified. These compounds are members of polyene macrocycles, pyrroloindole alkaloids, angucyclines, and leupeptins chemical families. Two of the identified compounds correspond to a new fungal metabolite (29) and a new actinobacterial angucycline-derivative (23). Our results revealed a substantial arsenal of small molecules induced by microbial interactions, as we begin to unravel the complexity of microbial interactions associated with endophytic systems.
Lipid Driven Nanodomains in Giant Lipid Vesicles are Fluid and Disordered
Authors: Koukalová Alena , Amaro Mariana , Aydogan Gokcan , Gröbner Gerhard , Williamson Philip T. F. , Mikhalyov Ilya , Hof Martin , Šachl Radek
Published: July 2017

It is a fundamental question in cell biology and biophysics whether sphingomyelin (SM)- and cholesterol (Chol)- driven nanodomains exist in living cells and in model membranes. Biophysical studies on model membranes revealed SM and Chol driven micrometer-sized liquid-ordered domains. Although the existence of such microdomains has not been proven for the plasma membrane, such lipid mixtures have been often used as a model system for ‘rafts’. On the other hand, recent super resolution and single molecule results indicate that the plasma membrane might organize into nanocompartments. However, due to the limited resolution of those techniques their unambiguous characterization is still missing. In this work, a novel combination of Förster resonance energy transfer and Monte Carlo simulations (MC-FRET) identifies directly 10 nm large nanodomains in liquid-disordered model membranes composed of lipid mixtures containing SM and Chol. Combining MC-FRET with solid-state wide-line and high resolution magic angle spinning NMR as well as with fluorescence correlation spectroscopy we demonstrate that these nanodomains containing hundreds of lipid molecules are fluid and disordered. In terms of their size, fluidity, order and lifetime these nanodomains may represent a relevant model system for cellular membranes and are closely related to nanocompartments suggested to exist in cellular membranes.
Alterations of microbiota structure in the larynx relevant to laryngeal carcinoma
Authors: Gong Hongli , Shi Yi , Xiao Xiyan , Cao Pengyu , Wu Chunping , Tao Lei , Hou Dongsheng , Wang Yuezhu , Zhou Liang
Published: July 2017

The microbial communities that inhabit the laryngeal mucosa build stable microenvironments and have the potential to influence the health of the human throat. However, the associations between the microbiota structure and laryngeal carcinoma remain uncertain. Here, we explored this question by comparing the laryngeal microbiota structure in laryngeal cancer patients with that in control subjects with vocal cord polyps through high-throughput pyrosequencing. Overall, the genera Streptococcus, Fusobacterium, and Prevotella were prevalent bacterial populations in the laryngeal niche. Tumor tissue samples and normal tissues adjacent to the tumor sites (NATs) were collected from 31 laryngeal cancer patients, and the bacterial communities in laryngeal cancer patients were compared with control samples from 32 subjects. A comparison of the laryngeal communities in the tumor tissues and the NATs showed higher α-diversity in cancer patients than in control subjects, and the relative abundances of seven bacterial genera differed among the three groups of samples. Furthermore, the relative abundances of ten bacterial genera in laryngeal cancer patients differed substantially from those in control subjects. These findings indicate that the laryngeal microbiota profiles are altered in laryngeal cancer patients, suggesting that a disturbance of the microbiota structure might be relevant to laryngeal cancer.
Brain regionalization genes are co-opted into shell field patterning in Mollusca
Authors: Wollesen Tim , Scherholz Maik , Rodríguez Monje Sonia Victoria , Redl Emanuel , Todt Christiane , Wanninger Andreas
Published: July 2017

The ‘brain regionalization genes’ Six3/6, Otx, Pax2/5/8, Gbx, and Hox1 are expressed in a similar fashion in the deuterostome, ecdysozoan, and the cephalopod brain, questioning whether this holds also true for the remaining Mollusca. We investigated developmental Gbx-expression in representatives of both molluscan sister groups, the Aculifera and Conchifera. Gbx is expressed in the posterior central nervous system of an aculiferan polyplacophoran and solenogaster but not in a conchiferan bivalve suggesting that Gbx, together with Six3/6, Otx, Pax2/5/8, and Hox1, is involved in central nervous system regionalization as reported for other bilaterians. Gbx is, however, also expressed in the anterior central nervous system, i.e. the anlagen of the cerebral ganglia, in the solenogaster, a condition not reported for any other bilaterian so far. Strikingly, all Gbx-orthologs and the other ‘posterior brain regionalization genes’ such as Pax2/5/8 and Hox1 are expressed in the mantle that secretes shell(s) and spicules of mollusks (except cephalopods). In bivalves, the ancestral condition has even been lost, with Gbx and Pax2/5/8 not being expressed in the developing central nervous system anymore. This suggests an additional role in the formation of the molluscan shell field(s) and spicule-bearing cells, key features of mollusks.