bluuebunny/crossref_metadata_2025 huggingface dataset:
Long Chain Effects on DNA‐Binding and Cytotoxicity to Cancer Cells in Metallo‐Supramolecular Oligomers
Authors: Rana Utpal , Hossain Md. Delwar , Chakraborty Chanchal , Nagano Reiko , Morita Hiromi , Hattori Shinya , Minowa Takashi , Higuchi Masayoshi
Published: July 2018

We synthesized Fe(II)‐based metallo‐supramolecular oligomers with the different degree of polymerization (DP) (DP‐1, −5 and −10) by changing the molar ratio of Fe(II) acetate and bis(terpyridyl)benzene to 1:2, 5:6, and 10:11, respectively. We investigated the chain length effects on the binding affinity to DNA and cytotoxicity to cancer cells in the oligomers. DP‐10 showed five‐time larger DNA binding constant and four‐time stronger cytotoxicity than DP‐1. We also studied the cell apoptosis assay using annexin V‐FITC/PI staining by flow cytometry and revealed that the ratio of early and late apoptosis cells increased from 15.6% (DP‐1) to 61.4% (DP‐10) with increasing the chain length.
Mixing of Complex Fluids in a Cylindrical Tank by a Modified Anchor Impeller
Authors: Ameur Houari , Ghenaim Abdellah
Published: July 2018

The mixing of shear thinning fluids in a cylindrical vessel has been investigated in this paper via numerical simulation. The agitation is ensured by a modified anchor impeller (MAI): it consists of curved blade turbine (CBT) mounted on a classical anchor impeller (CAI). These agitators were mounted in single and combined configurations (co‐axial). The effects of agitation rate, design of the stirred system and curvature of the bottomed arm of anchor on the fluid circulation, well‐stirred region size and power consumption have been studied. The obtained results revealed that the modified anchor impeller (i. e. the combination of CBT with CAI) performs better than the classical anchor impeller.
A Direct Z‐Scheme Van Der Waals Heterojunction (WO3·H2O/g‐C3N4) for High Efficient Overall Water Splitting under Visible‐Light
Authors: Yang Yurong , Qiu Min , Li Liu , Pi Yanmei , Yan Guomin , Yang Lei
Published: July 2018

Achieving overall water splitting is crucial for the effective application of recycling solar energy. Here, we design and construct a direct Z‐scheme van der Waals heterojunction composed by ultrathin WO3·H2O and g‐C3N4 nanosheets to achieve efficient overall water splitting without adding any sacrificial agents. This WO3·H2O/g‐C3N4 system can efficiently transport the electrons, which leading to a considerable improvement in the photocatalytic performance. Due to the suitable band edge potentials for H2, O2 evolution, and remarkable charge transfer, the direct WO3·H2O/g‐C3N4 Z‐scheme system exhibits prominent photocatalytic activity for both H2 and O2 production under visible‐light illumination, the H2, O2 production rate up to 482 and 232 µmol g−1 h−1 respectively, which is greatly higher than the H2 evolution of g‐C3N4 nanosheets (109 µmol h−1 g−1) and the O2 evolution of WO3·H2O nanosheets (57 µmol h−1 g−1) under the same condition. The measured quantum efficiency of the WO3·H2O/g‐C3N4 heterojunction reaches 6.2% at 420 nm.
Elucidating the Mechanism of an RbF Post Deposition Treatment in CIGS Thin Film Solar Cells
Authors: Kodalle Tim , Heinemann Marc D. , Greiner Dieter , Yetkin Hasan A. , Klupsch Michael , Li Chen , van Aken Peter A. , Lauermann Iver , Schlatmann Rutger , Kaufmann Christian A.
Published: July 2018

The impact of a rubidium fluoride post deposition treatment (RbF‐PDT) on the material and device properties of Cu(In,Ga)Se2 (CIGS) thin films and corresponding solar cells is investigated. The structure and device properties of CIGS with different PDT duration are compared. With longer PDT duration, which equals a higher amount of RbF deposited on the CIGS absorber layer, a clear trade‐off is observed between increasing open‐circuit‐voltage (VOC) and decreasing fill factor (FF). An optimum of the PDT duration is found increasing the efficiency by about 0.8% (absolute) compared to the Rb‐free reference device. The mechanisms behind the increased VOC are explored by various characterization methods and identified as a combination of increased carrier concentration and reduced recombination rates in the device. Possible origins for these mechanisms are discussed. Furthermore numerical simulations are used to analyze the detrimental effect of the PDT on the FF. It is found that thermally activated alkali migration into the transparent front contact could create acceptor states there, which could explain the observed FF‐loss.
Alpha4‐overexpressing HL7702 cells can counteract microcystin‐LR effects on cytoskeletal structure
Authors: Huang Pu , Wang Sha , Weng Dengpo , Xu Lihong
Published: July 2018

Our previous studies indicated that α4 was involved in the toxicity of MC‐LR on the cytoskeleton via the change of PP2A activity in HEK 293. To explore the role of α4 in MC‐LR toxicity via PP2A regulation in different cell lines, the HL7702 cell overexpressing α4 protein was exposed to MC‐LR, and the change of PP2A, cytoskeletal structure, and cytoskeleton‐related proteins were investigated. The results showed that PP2A activity was decreased, PP2A/C subunit expression and phosphorylation (Tyr307) increased significantly, but methylation (Leu 309)clearly decreased. The structure of the actin filaments and microtubules (MTs) remained unchanged, and the expression and phosphorylation of the cytoskeleton‐related proteins showed different changes. In addition, the main components of the MAPK pathway, JNK, P38, and ERK1/2, were activated together. Our results indicated that elevated α4 expression did confer some resistance to MC‐LR‐induced cytoskeletal changes, but the responses of different cell lines to MC‐LR, under the α4‐overexpression condition, are not exactly the same.
National Security Considerations for a Binding Instrument on Managing Biodiversity Beyond National Jurisdiction
Authors: Kraska James
Published: July 2018

The effort to negotiate and adopt a legally binding instrument to manage marine biodiversity beyond areas of national jurisdiction (BBNJ) implicates national security interests both directly and tangentially. First, negotiations for any agreement will contend with the long-standing concept that the oceans are reserved for “peaceful purposes.” The maritime powers will insist that the concept, which reflects customary law and the practice of virtually all states, does not demilitarize the oceans. Second, any BBNJ treaty must overcome two interrelated spatial issues: the geographic parameters of what constitutes “areas beyond national jurisdiction” when those maritime boundaries are often uncertain, and how measures to protect the environment interact with military activities in those areas. Naval powers will insist that requisite marine protected areas (MPAs) and associated protective measures do not diminish naval freedom of navigation and other military uses of the sea. Third, BBNJ negotiations will be compelled to address how a new treaty will relate to the United Nations Convention on the Law of the Sea (UNCLOS), a host of other treaties, and customary norms. Imperfect as the contemporary global order of the oceans is, major maritime powers and even middle powers will seek to protect it and resist efforts at radical change that may destabilize existing regimes in pursuit of an ephemeral gain for BBNJ. This strategic interest in international stability, while understandable, unintentionally creates inertia that is likely to frustrate the most progressive proponents of BBNJ. Fourth, more broadly, any treaty is likely to affect marine ecosystem services and perhaps marine genetic resources (MGR), which help propel the “blue economy” and undergird national security. We may expect most coastal states to continue to jealously protect their exclusive rights to the living and nonliving resources offshore, and even to propose expansion of those rights and jurisdiction to “adjacent areas.” The most developed states, for their part, are unlikely to agree to any text that diminishes their rights to intellectual property related to marine biotechnology, which is a strategic sector for bio-weapons research and defense. In short, states with advanced military capabilities, and major maritime powers in particular, are unlikely to support more than incremental change to the regimes reflected in UNCLOS.
Improving the National Flood Insurance Program
Authors: KUNREUTHER HOWARD
Published: July 2018

This paper highlights factors that need to be considered for improving the National Flood Insurance Program in the USA to address the biases that lead individuals to not protect themselves against low-probability, high-consequence flood events. The errors that individuals exhibit in deciding not to purchase insurance or invest in loss reduction measures prior to a disaster can be traced to the effects of six biases: myopia, amnesia, optimism, inertia, simplification and herding. Along with two guiding principles for insurance, a behavioral risk audit can assist in designing a strategy using concepts from choice architecture coupled with economic incentives to encourage property owners in hazard-prone areas to purchase insurance and invest in cost-effective adaptation measures to protect themselves against future disaster losses.
Along the Margins? The Later Bronze Age Seascapes of Western Ireland
Authors: Quinn Colin P. , Kuijt Ian , Goodale Nathan , Ó Néill John
Published: July 2018

This article presents the results of multi-scalar investigations into the Later Bronze Age (LBA; 1500–600bc) landscape of Inishark in County Galway, Ireland. The European LBA along the Atlantic coast was characterized by the development of long-distance maritime exchange systems that transformed environmentally marginal seascapes into a corridor of human interaction and movement of goods and people. Archaeological survey, test excavation, and radiocarbon analysis documented the LBA occupation on Inishark. The communities living on Inishark and other small islands on the western Irish coast were on the periphery of both the European continent and of the elite spheres of influence at hillforts in Ireland; yet they were connected to the Atlantic maritime exchange routes. A focus on small coastal islands contributes to a better understanding of LBA socioeconomic systems and the development of social complexity in Bronze Age societies.
Employment in Northern Ireland's Civil Service: Social Barriers and Hyperbole Mean Disabled Need Not Apply
Authors: Olsen Jason
Published: July 2018

The representation of people with disabilities in the Northern Ireland Civil Service (NICS) is approximately 44% less than that seen in the civil services of the United States (US) and Great Britain (GB; i.e., the United Kingdom sans Northern Ireland). Various proactive approaches to employing people with disabilities are cited for the success of the US and GB's efforts to increase the representation of disabled people in their civil services. This is important because governments as employers can be the catalyst for large-scale social change. The US and GB governments have demonstrated an intention to be this catalyst. They have done this by (a) establishing goals for the hiring of disabled people; (b) naming executives responsible for reaching these hiring goals; (c) utilising special hiring authorities; (d) executing guaranteed interview schemes; and (e) applying regulations and laws designed to employ and protect people with disabilities. These activities could be adopted in Northern Ireland (NI) to address the current inequalities in the NICS. However, the question remains whether a government that believes it has achieved disability equality in its civil service, despite comparators that say otherwise, can or will make such a concerted effort. An analysis of over 60 US, GB, and NI government and assembly documents, reports, and laws are examined and compared through the lens of critical disability theory (CDT) to identify the disconnect between the representations and the reality of figures presented about the inclusion of those with disabilities in the NICS.
Robustness of nearshore vortices
Authors: McWilliams James C. , Akan Cigdem , Uchiyama Yusuke
Published: July 2018

Coherent vortices with horizontal swirl arise spontaneously in the wave-driven nearshore surf zone. Here, a demonstration is made of the much greater robustness of coherent barotropic dipole vortices on a sloping beach in a 2D shallow-water model compared with fully 3D models either without or with stable density stratification. The explanation is that active vortex tilting and stretching or instability in 3D disrupt an initially barotropic dipole vortex. Without stratification in 3D, the vorticity retains a dipole envelope structure but is internally fragmented. With stratification in 3D, the disrupted vortex reforms as a coherent but weaker surface-intensified baroclinic dipole vortex. An implication is that barotropic or depth-integrated dynamical models of the wave-driven surf zone misrepresent an important aspect of surf-eddy behaviour.
DISTRIBUTION OF GALOIS GROUPS OF MAXIMAL UNRAMIFIED 2-EXTENSIONS OVER IMAGINARY QUADRATIC FIELDS
Authors: SASAKI SOSUKE
Published: July 2018

Let$k$be an imaginary quadratic field with$\operatorname{Cl}_{2}(k)\simeq V_{4}$. It is known that the length of the Hilbert$2$-class field tower is at least$2$. Gerth (On 2-class field towers for quadratic number fields with$2$-class group of type$(2,2)$, Glasgow Math. J.40(1) (1998), 63–69) calculated the density of$k$where the length of the tower is$1$; that is, the maximal unramified$2$-extension is a$V_{4}$-extension. In this paper, we shall extend this result for generalized quaternion, dihedral, and semidihedral extensions of small degrees.
Modeling-Related Processes With an Excess of Zeros
Authors: Carlson David
Published: July 2018

Political science research frequently models binary or ordered outcomes involving related processes. However, traditional modeling of these outcomes ignores common data issues and cannot capture nuances. There is often an excess of zeros, the observed outcomes for different actors are inherently related, and competing actors may respond to the same factors differently. This paper extends existing models and develops a zero-inflated multivariate ordered probit to simultaneously address these issues. This model performs better than existing models at capturing the true parameters of interest, estimates the nature of the related processes, and captures the differences in actors’ decision-making. I demonstrate these benefits through simulation exercises and an application to party behavior in Mexico.
Variation in the composition and diversity of ground-layer herbs and shrubs in unburnt and burnt landscapes
Authors: Cleary Daniel F. R. , Eichhorn Karl A. O.
Published: July 2018

Forest fires pose an important threat to tropical rain-forest biodiversity. In the present study, we assessed ground layer (herb and shrub) communities in six differentially disturbed landscape plots in East Kalimantan, Indonesia, including primary and logged forest and once-, twice- and frequently-burnt forest. Overall, we recorded 175 species of herbs and shrubs; richness was highest in twice-burnt forest and lowest in logged forest. Vegetation and topographical variables including the percentage of the plot burnt and tree abundance were significant predictors of variation in composition. The main compositional gradient showed a clear distinction between subplots in unburnt versus burnt forest. A subset of subplots in burnt forest, however, clustered together with subplots from unburnt forest. These plots were located in a network of relatively unscathed forest along floodplains that persisted in the burnt-forest matrix. Small plant species associated with unburnt forest included several species of Dryopteridaceae, Marantaceae and Rubiaceae. Species associated with once- and twice-burnt forest included Mikania scandens (Compositae), Microlepia speluncae (Dennstaedtiaceae), Nephrolepis cf. biserrata (Nephrolepidaceae), Lygodium microphyllum (Schizaeaceae) and Hornstedtia cf. reticulata (Zingiberaceae). The frequently-burnt landscape plot was characterized by a high cover of the grass species Imperata cylindrica and the invasive exotic shrub Chromolaena odorata. Importantly, these species and other exotics had also invaded the once- and twice-burnt forest and represent a potential threat to forest recovery.
Additive correlation and the inverse problem for the large sieve
Authors: HANSON BRANDON
Published: July 2018

Let A ⊆ [1, N] be a set of integers with |A| ≫ $\sqrt N$. We show that if A avoids about p/2 residue classes modulo p for each prime p, then A must correlate additively with the squares S = {n2 : 1 ≤ n ≤ $\sqrt N$}, in the sense that we have the additive energy estimate
$$
E(A,S)\gg N\log N.
$$
This is, in a sense, optimal.
Travel distance and human movement predict paths of emergence and spatial spread of chikungunya in Thailand
Authors: Chadsuthi S. , Althouse B. M. , Iamsirithaworn S. , Triampo W. , Grantz K. H. , Cummings D. A. T.
Published: July 2018

Human movement contributes to the probability that pathogens will be introduced to new geographic locations. Here we investigate the impact of human movement on the spatial spread of Chikungunya virus (CHIKV) in Southern Thailand during a recent re-emergence. We hypothesised that human movement, population density, the presence of habitat conducive to vectors, rainfall and temperature affect the transmission of CHIKV and the spatiotemporal pattern of cases seen during the emergence. We fit metapopulation transmission models to CHIKV incidence data. The dates at which incidence in each of 151 districts in Southern Thailand exceeded specified thresholds were the target of model fits. We confronted multiple alternative models to determine which factors were most influential in the spatial spread. We considered multiple measures of spatial distance between districts and adjacency networks and also looked for evidence of long-distance translocation (LDT) events. The best fit model included driving-distance between districts, human movement, rubber plantation area and three LDT events. This work has important implications for predicting the spatial spread and targeting resources for control in future CHIKV emergences. Our modelling framework could also be adapted to other disease systems where population mobility may drive the spatial advance of outbreaks.
A review of select minerals influencing the haematopoietic process
Authors: Oliveira Dalila Cunha , Nogueira-Pedro Amanda , Santos Ed Wilson , Hastreiter Araceli , Silva Graziela Batista , Borelli Primavera , Fock Ricardo Ambrósio
Published: July 2018

Micronutrients are indispensable for adequate metabolism, such as biochemical function and cell production. The production of blood cells is named haematopoiesis and this process is highly consuming due to the rapid turnover of the haematopoietic system and consequent demand for nutrients. It is well established that micronutrients are relevant to blood cell production, although some of the mechanisms of how micronutrients modulate haematopoiesis remain unknown. The aim of the present review is to summarise the effect of Fe, Mn, Ca, Mg, Na, K, Co, iodine, P, Se, Cu, Li and Zn on haematopoiesis. This review deals specifically with the physiological requirements of selected micronutrients to haematopoiesis, showing various studies related to the physiological requirements, deficiency or excess of these minerals on haematopoiesis. The literature selected includes studies in animal models and human subjects. In circumstances where these minerals have not been studied for a given condition, no information was used. All the selected minerals have an important role in haematopoiesis by influencing the quality and quantity of blood cell production. In addition, it is highly recommended that the established nutrition recommendations for these minerals be followed, because cases of excess or deficient mineral intake can affect the haematopoiesis process.
Introduction to generalized type systems
Authors: Barendregt Henk
Published: July 2018

Programming languages often come with type systems. Some of these are simple, others are sophisticated. As a stylistic representation of types in programming languages several versions of typed lambda calculus are studied. During the last 20 years many of these systems have appeared, so there is some need of classification. Working towards a taxonomy, Barendregt (1991) gives a fine-structure of the theory of constructions (Coquand and Huet 1988) in the form of a canonical cube of eight type systems ordered by inclusion. Berardi (1988) and Terlouw (1988) have independently generalized the method of constructing systems in the λ-cube. Moreover, Berardi (1988, 1990) showed that the generalized type systems are flexible enough to describe many logical systems. In that way the well-knownpropositions-as-typesinterpretation obtains a nice canonical form.
Drawing matter: Plan
Authors: Allen Stan , Hobhouse Niall , Mallinson Helen
Published: July 2018

Over the course of an intensive day-long session, the authors combed the Drawing Matter archives for exemplary plan drawings. Their selections are presented here in pairs, based on visual rhymes or striking contrasts, on cross-historical comparisons or the persistence of plan-making techniques over time.

The architectural plan drawing is a paradoxical sort of object. In principle, an instrument that should be rendered obsolete by the act of construction, it nonetheless remains the most intensive and compact description of an architectural idea.

‘Plan’ is a verb as well as a noun, and implies a path toward a specified outcome. The plan is fundamentally optimistic, countering entropy with order, and this anticipatory quality is embedded in the logic of the plan itself. Architects make drawings for buildings that do not yet exist. An architectural plan is an empty geometric scaffold that awaits both construction and inhabitation.

But the plan also works retrospectively: it was the primary technical means employed in the measuring and recording of ancient architectures that was so fundamental to the education of a classical architect. And these drawings affirm that such reconstructions, far from being rote academic exercises, draw deeply on the architect's creative intelligence. In fact, we would argue that the conceptual power of the plan as a working instrument is precisely its capacity to function simultaneously as an analytical and projective device, poised between past histories and future possibilities.

This collection of images makes a case for the continued relevance of the plan today as evidenced by the diversity, conceptual density and shear visual power of these artefacts.
Beyond instrumental use: a study of writing on architectural drawings in the late twentieth century
Authors: Bafna Sonit , Kim Hoyoung
Published: July 2018

The 1980s witnessed a sudden rise of writing and thinking about architectural drawings and their conventions. At about the same time, there also emerged a trend of a new type of presentational drawing in architecture, in which drawings were very complex to the point of undecipherability, graphically sophisticated, and sometimes seemingly created for their own sake rather than to represent a particular architectural project. Upon reviewing the texts on drawings from this period, two important insights are made about the use of presentational drawings in architectural practice and their relation to theory. First, that making of architectural drawings can constitute practice in its own right and such practice, if developed experimentally, leads theory, rather than lagging it and serving to validate it. Second, architectural drawings, over and above communicating information about their subject matter, can also function as a means to create social networks of discursive practice. These insights lead to an unexpected question concerning the distinctiveness of architectural practice itself.
Supervisor practice when guiding therapists working with depression: the impact of supervisor and patient characteristics
Authors: Simpson-Southward Chloe , Waller Glenn , Hardy Gillian
Published: July 2018

Currently recommended psychotherapies for depression are not always delivered in a consistent manner. There is an assumption that the use of clinical supervision will ensure reliable treatment and patient recovery. However, there is limited research supporting this assumption. This study explored the role of supervision in the treatment of depression. In particular, it examined how supervisors’ own characteristics and those of patients can influence the focus of supervision sessions. Clinical supervisors who worked with cognitive behavioural therapy (CBT) therapists treating depression cases were asked to indicate their supervision focus for three different patient vignettes. These vignettes varied in clinical complexity. Participants’ intolerance to uncertainty and their self-esteem were also assessed. Supervisors tended to focus their supervisees on the use of evidence-based therapeutic techniques for both straightforward and complex cases. However, their approach was less evidence-based for diffuse cases. Three supervisory types emerged: an ‘Alliance- and Technique-Focused’ group, a ‘Case Management-Focused’ group, and an ‘Unfocused’ group. Personal characteristics of the supervisors varied across the groups. The content of supervision sessions is influenced by factors from outside the therapy process. These factors might cause supervisors to avoid focusing on evidence-based aspects of therapy, thus feeding therapist drift. Suggestions are made for new supervision protocols that consider the supervisor's personal characteristics.
Shear Strain Energy Change Caused by the Interplate Coupling Along the Nankai Trough: An Integration Analysis Using Stress Tensor Inversion and Slip‐Deficit Inversion
Authors: Saito Tatsuhiko , Noda Akemi , Yoshida Keisuke , Tanaka Sachiko
Published: July 2018

In the Nankai Trough, southwest Japan, the Philippine Sea plate descends beneath the Eurasian plate. The locking on the plate interface causes stress change in the seismogenic lithosphere of the Eurasian plate. This interplate locking does not always result in stress accumulation but can cause stress release. The present study employs shear strain energy to determine whether the stress is accumulated or released in the seismogenic zone. While most studies employed a shear stress assuming a fault plane, the shear strain energy is more feasible for the stress accumulation/release mapping because the assumption of the fault plane is not required. First, we estimated the directions of the principal stress axes and the stress ratio of the background stress field by analyzing ~8,000 focal mechanisms. In the Chugoku region, the maximum compression axis is in the E‐W direction. We then calculated the stress change due to the slip deficit along the Nankai Trough. The stress change showed that the maximum compression is in the N‐S direction in the Chugoku region. By using both the background stress and the stress fluctuation, we estimated the shear strain energy change caused by the slip deficit. The shear strain energy is decreased due to the interplate locking in the Chugoku region. We also statistically compared the shear strain energy change with the seismicity in southwestern Japan and found that the seismicity is high where the strain energy increases.
Thank You to Our 2017 Peer Reviewers
Authors: Pincus Robert , Dirmeyer Paul A. , Griffies Stephen
Published: July 2018

As the editors of a scientific journal we are privileged to have front‐row seats to the peer review process. We watch as reviewers hold a mirror up to authors' work, identifying weakness in conception or expression, suggesting refinements, prodding authors to clarify a point or better support an argument. The process is almost always respectful even if it's not always comfortable. The final papers are uniformly better for this input. At JAMES we are fortunate to have a pool of reviewers who volunteer their time, insight, and intelligence to improve the work of their colleagues and peers, usually without receiving any credit themselves. Though the journal is small the task is not: Just in 2017, we received 628 reviews by 432 individuals. On behalf of the entire editorial board we thank you all for your selfless contributions to our community.
Gabrb2-knockout mice displayed schizophrenia-like and comorbid phenotypes with interneuron–astrocyte–microglia dysregulation
Authors: Yeung Rigil K. , Xiang Zheng-Hua , Tsang Shui-Ying , Li Rui , Ho Timothy Y. C. , Li Qi , Hui Chok-King , Sham Pak-Chung , Qiao Ming-Qi , Xue Hong
Published: July 2018

Intronic polymorphisms of the GABAA receptor β2 subunit gene (GABRB2) under adaptive evolution were associated with schizophrenia and reduced expression, especially of the long isoform which differs in electrophysiological properties from the short isoform. The present study was directed to examining the gene dosage effects of Gabrb2 in knockout mice of both heterozygous (HT) and homozygous (KO) genotypes with respect to possible schizophrenia-like and comorbid phenotypes. The KO mice, and HT mice to a lesser extent, were found to display prepulse inhibition (PPI) deficit, locomotor hyperactivity, stereotypy, sociability impairments, spatial-working and spatial-reference memory deficits, reduced depression and anxiety, and accelerated pentylenetetrazol (PTZ)-induced seizure. In addition, the KO mice were highly susceptible to audiogenic epilepsy. Some of the behavioral phenotypes showed evidence of imprinting, gender effect and amelioration by the antipsychotic risperidone, and the audiogenic epilepsy was inhibited by the antiepileptic diazepam. GABAergic parvalbumin (PV)-positive interneuron dystrophy, astrocyte dystrophy, and extensive microglia activation were observed in the frontotemporal corticolimbic regions, and reduction of newborn neurons was observed in the hippocampus by immunohistochemical staining. The neuroinflammation indicated by microglial activation was accompanied by elevated brain levels of oxidative stress marker malondialdehyde (MDA) and the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). These extensive schizophrenia-like and comorbid phenotypes brought about by Gabrb2 knockout, in conjunction with our previous findings on GABRB2 association with schizophrenia, support a pivotal role of GABRB2 in schizophrenia etiology.
RETRACTED ARTICLE: Annonacin promotes selective cancer cell death via NKA-dependent and SERCA-dependent pathways
Authors: Yiallouris Andreas , Patrikios Ioannis , Johnson Elizabeth O. , Sereti Evangelia , Dimas Konstantinos , De Ford Cristian , Fedosova Natalia U. , Graier Wolfgang F. , Sokratous Kleitos , Kyriakou Kyriakos , Stephanou Anastasis
Published: July 2018

In the healthcare sector, phytocompounds are known to be beneficial by contributing or alleviating a variety of diseases. Studies have demonstrated the progressive effects of phytocompounds on immune-related diseases and to exhibit anticancer effects. Graviola tree is an evergreen tree with its extracts (leafs and seeds) been reported having anticancer properties, but the precise target of action is not clear. Using an in silico approach, we predicted that annonacin, an Acetogenin, the active agent found in Graviola leaf extract (GLE) to potentially act as a novel inhibitor of both sodium/potassium (NKA) and sarcoplasmic reticulum (SERCA) ATPase pumps. We were able to validate and confirm the in silico studies by showing that GLE inhibited NKA and SERCA activity in intact cells. In the present study, we also demonstrated the antiproliferative and anticancer effects of GLE in a variety of cancer cell lines with limited toxic effects on non-transformed cells. Moreover, our results revealed that known inhibitors of both NKA and SERCA pumps could also promote cell death in several cancer cell lines. In addition, a mouse xenograft cancer model showed GLE as able to reduce tumor size and progression. Finally, bioprofiling studies indicated a strong correlation between overexpression of both NKA and SERCA gene expression vs. survival rates. Overall, our results demonstrated that GLE can promote selective cancer cell death via inhibiting NKA and SERCA, and thus can be considered as a potential novel treatment for cancer. After molecular analysis of GLE by liquid chromatography–mass spectrometry and ESI–QTOF–MS analysis, it was found that the MS spectrum of the high abundant chromatographic peak purified sample highly consisted of annonacin.
BET bromodomain inhibitor JQ1 preferentially suppresses EBV-positive nasopharyngeal carcinoma cells partially through repressing c-Myc
Authors: Li Ning , Yang Lu , Qi Xue-Kang , Lin Yu-Xin , Xie Xinhua , He Gui-Ping , Feng Qi-Sheng , Liu Ling-Rui , Xie Xiaoming , Zeng Yi-Xin , Feng Lin
Published: July 2018

The management of advanced nasopharyngeal carcinoma (NPC) remains a challenge. The ubiquitous nature of Epstein–Barr virus (EBV) infection in nonkeratinizing NPC has forced us to investigate novel drugs for NPC in the presence of EBV. In this study, we performed a small-scale screening of a library of compounds that target epigenetic regulators in paired EBV-positive and EBV-negative NPC cell lines. We found that bromodomain and extra-terminal (BET) inhibitor JQ1 preferentially inhibits the growth of EBV-positive NPC cells. JQ1 induces apoptosis, decreases cell proliferation and enhances the radiosensitivity in NPC cells, especially EBV-positive cells. Significantly, JQ1-induced cell death is c-Myc-dependent. Notably, RNA-seq analysis demonstrated that JQ1 represses TP63, TP53 and their targets. JQ1 also lessens the expression of PD-L1 in NPC. Moreover, the high potency of JQ1 in NPC cells was further confirmed in vivo in CNE2-EBV+ tumor-bearing mice. These findings indicate that JQ1 is a promising therapeutic candidate for advanced NPC.
Glutathione depletion induces ferroptosis, autophagy, and premature cell senescence in retinal pigment epithelial cells
Authors: Sun Yun , Zheng Yingfeng , Wang Chunxiao , Liu Yizhi
Published: July 2018

Glutathione (GSH) protects against oxidative damage in many tissues, including retinal pigment epithelium (RPE). Oxidative stress-mediated senescence and death of RPE and subsequent death of photoreceptors have been observed in age-related macular degeneration (AMD). Although the consequences of GSH depletion have been described previously, questions remain regarding the molecular mechanisms. We herein examined the downstream effects of GSH depletion on stress-induced premature senescence (SIPS) and cell death in human RPE cells. Briefly, cultured ARPE-19 cells were depleted of GSH using: (1) incubation in cystine (Cys2)-free culture medium; (2) treatment with buthionine sulphoximine (BSO, 1000 µM) to block de novo GSH synthesis for 24–48 h; or (3) treatment with erastin (10 µM for 12–24 h) to inhibit Cys2/glutamate antiporter (system xc−). These treatments decreased cell viability and increased both soluble and lipid reactive oxygen species (ROS) generation but did not affect mitochondrial ROS or mitochondrial mass. Western blot analysis revealed decreased expression of ferroptotic modulator glutathione peroxidase 4 (GPX4). Increased autophagy was apparent, as reflected by increased LC3 expression, autophagic vacuoles, and autophagic flux. In addition, GSH depletion induced SIPS, as evidenced by increased percentage of the senescence-associated β-galactosidase-positive cells, increased senescence-associated heterochromatin foci (SAHF), as well as cell cycle arrest at the G1 phase. GSH depletion-dependent cell death was prevented by selective ferroptosis inhibitors (8 μM Fer-1 and 600 nM Lip-1), iron chelator DFO (80 μM), as well as autophagic inhibitors Baf-A1 (75 nM) and 3-MA (10 mM). Inhibiting autophagy with Baf-A1 (75 nM) or 3-MA (10 mM) promoted SIPS. In contrast, inducing autophagy with rapamycin (100 nM) attenuated SIPS. Our findings suggest that GSH depletion induces ferroptosis, autophagy, and SIPS. In addition, we found that autophagy is activated in the process of ferroptosis and reduces SIPS, suggesting an essential role of autophagy in ferroptosis and SIPS.
Exosomal secretion of α-synuclein as protective mechanism after upstream blockage of macroautophagy
Authors: Fussi Natascha , Höllerhage Matthias , Chakroun Tasnim , Nykänen Niko-Petteri , Rösler Thomas W. , Koeglsperger Thomas , Wurst Wolfgang , Behrends Christian , Höglinger Günter U.
Published: July 2018

Accumulation of pathological α-synuclein aggregates plays a major role in Parkinson’s disease. Macroautophagy is a mechanism to degrade intracellular protein aggregates by wrapping them into autophagosomes, followed by fusion with lysosomes. We had previously shown that pharmacological activation of macroautophagy protects against α-synuclein-induced toxicity in human neurons. Here, we hypothesized that inhibition of macroautophagy would aggravate α-synuclein-induced cell death.

Unexpectedly, inhibition of autophagosome formation by silencing of ATG5 protected from α-synuclein-induced toxicity. Therefore, we studied alternative cellular mechanisms to compensate for the loss of macroautophagy. ATG5 silencing did not affect the ubiquitin–proteasome system, chaperone systems, chaperone-mediated autophagy, or the unfolded protein response. However, ATG5 silencing increased the secretion of α-synuclein via exosomes. Blocking exosomal secretion exacerbated α-synuclein-induced cell death.

We conclude that exosomal secretion of α-synuclein is increased after impaired formation of autophagosomes to reduce the intracellular α-synuclein burden. This compensatory mechanism prevents α-synuclein-induced neuronal cell death.
Single neurons may encode simultaneous stimuli by switching between activity patterns
Authors: Caruso Valeria C. , Mohl Jeff T. , Glynn Christopher , Lee Jungah , Willett Shawn M. , Zaman Azeem , Ebihara Akinori F. , Estrada Rolando , Freiwald Winrich A. , Tokdar Surya T. , Groh Jennifer M.
Published: July 2018

How the brain preserves information about multiple simultaneous items is poorly understood. We report that single neurons can represent multiple stimuli by interleaving signals across time. We record single units in an auditory region, the inferior colliculus, while monkeys localize 1 or 2 simultaneous sounds. During dual-sound trials, we find that some neurons fluctuate between firing rates observed for each single sound, either on a whole-trial or on a sub-trial timescale. These fluctuations are correlated in pairs of neurons, can be predicted by the state of local field potentials prior to sound onset, and, in one monkey, can predict which sound will be reported first. We find corroborating evidence of fluctuating activity patterns in a separate dataset involving responses of inferotemporal cortex neurons to multiple visual stimuli. Alternation between activity patterns corresponding to each of multiple items may therefore be a general strategy to enhance the brain processing capacity, potentially linking such disparate phenomena as variable neural firing, neural oscillations, and limits in attentional/memory capacity.
Bottle-grade polyethylene furanoate from ring-opening polymerisation of cyclic oligomers
Authors: Rosenboom Jan-Georg , Hohl Diana Kay , Fleckenstein Peter , Storti Giuseppe , Morbidelli Massimo
Published: July 2018

Polyethylene furanoate (PEF) represents a promising renewable resource-based bioplastic as replacement for fossil-based polyethylene terephthalate (PET) with improved material properties. However, the synthesis of PEF through conventional polycondensation remains challenging, since the time-intensive reaction leads to degradation and undesired discolouration of the product. Here we show the successful rapid synthesis of bottle-grade PEF via ring-opening polymerisation (ROP) from cyclic PEF oligomers within minutes, thereby avoiding degradation and discolouration. The melting point of such mixture of cyclic oligomers lies around 370 °C, well above the degradation temperature of PEF (~329 °C). This challenge can be overcome, exploiting the self-plasticising effect of the forming polymer itself (which melts around 220 °C) by initiation in the presence of a high boiling, yet removable, and inert liquid plasticiser. This concept yields polymer grades required for bottle applications (Mn > 30 kg mol−1, conversion > 95%, colour-free products), and can be extended to other diffusion-limited polymer systems.
Single-molecule insights into surface-mediated homochirality in hierarchical peptide assembly
Authors: Chen Yumin , Deng Ke , Lei Shengbin , Yang Rong , Li Tong , Gu Yuantong , Yang Yanlian , Qiu Xiaohui , Wang Chen
Published: July 2018

Homochirality is very important in the formation of advanced biological structures, but the origin and evolution mechanisms of homochiral biological structures in complex hierarchical process is not clear at the single-molecule level. Here we demonstrate the single-molecule investigation of biological homochirality in the hierarchical peptide assembly, regarding symmetry break, chirality amplification, and chirality transmission. We find that homochirality can be triggered by the chirality unbalance of two adsorption configuration monomers. Co-assembly between these two adsorption configuration monomers is very critical for the formation of homochiral assemblies. The site-specific recognition is responsible for the subsequent homochirality amplification and transmission in their hierarchical assembly. These single-molecule insights open up inspired thoughts for understanding biological homochirality and have general implications for designing and fabricating artificial biomimetic hierarchical chiral materials.
Highly efficient RNA-guided base editing in rabbit
Authors: Liu Zhiquan , Chen Mao , Chen Siyu , Deng Jichao , Song Yuning , Lai Liangxue , Li Zhanjun
Published: July 2018

Cytidine base editors (CBEs) and adenine base editors (ABEs), composed of a cytidine deaminase or an evolved adenine deaminase fused to Cas9 nickase, enable the conversion of C·G to T·A or A·T to G·C base pair in organisms, respectively. Here, we show that BE3 and ABE7.10 systems can achieve a targeted mutation efficiency of 53–88% and 44–100%, respectively, in both blastocysts and Founder (F0) rabbits. Meanwhile, this strategy can be used to precisely mimic human pathologies by efficiently inducing nonsense or missense mutations as well as RNA mis-splicing in rabbit. In addition, the reduced frequencies of indels with higher product purity are also determined in rabbit blastocysts by BE4-Gam, which is an updated version of the BE3 system. Collectively, this work provides a simple and efficient method for targeted point mutations and generation of disease models in rabbit.
Aberrant imprinting may underlie evolution of parthenogenesis
Authors: Kirioukhova Olga , Shah Jubin N. , Larsen Danaé S. , Tayyab Muhammad , Mueller Nora E. , Govind Geetha , Baroux Célia , Federer Michael , Gheyselinck Jacqueline , Barrell Philippa J. , Ma Hong , Sprunck Stefanie , Huettel Bruno , Wallace Helen , Grossniklaus Ueli , Johnston Amal J.
Published: July 2018

Genomic imprinting confers parent-of-origin-specific gene expression, thus non-equivalent and complementary function of parental genomes. As a consequence, genomic imprinting poses an epigenetic barrier to parthenogenesis in sexual organisms. We report aberrant imprinting in Boechera, a genus in which apomicts evolved from sexuals multiple times. Maternal activation of a MADS-box gene, a homolog of which is imprinted and paternally expressed in the sexual relative Arabidopsis, is accompanied by locus-specific DNA methylation changes in apomicts where parental imprinting seems to be relaxed.
Effect of temperature on the oxidation of Cu nanowires and development of an easy to produce, oxidation-resistant transparent conducting electrode using a PEDOT:PSS coating
Authors: Mardiansyah Dedi , Badloe Trevon , Triyana Kuwat , Mehmood Muhammad Q. , Raeis-Hosseini Niloufar , Lee Yoonkyung , Sabarman Harsojo , Kim Kyunghoon , Rho Junsuk
Published: July 2018

Oxidation can strongly influence the performance of Cu nanowires (CuNWs) by decreasing their conductivity. Here, we identify and investigate a way to prevent the oxidation process of CuNWs to maintain the high conducting performance of CuNWs as transparent electrodes. CuNWs were synthesised using an aqueous method. We prepared several temperature treatments (from 0–300 °C) to represent oxidation of CuNWs in different environments, to study the oxidation process and changes in morphology in detail. Depending on the temperature, smooth and uniform CuNWs exposed to oxidation produced rough Cu2O and CuO nanowires. We then suggest a method of protecting nanowires from oxidation, using the Mayer rod coating method to apply a layer of PEDOT:PSS to a transparent conducting film of CuNWs. The result indicates that this method of protection can protect the film, and maintain a stable, and constant resistance over of time, without effecting the excellent conductivity properties of pure CuNWs.
Simple Physical Model Unravels Influences of Chemokine on Shape Deformation and Migration of Human Hematopoietic Stem Cells
Authors: Ohta Takao , Monzel Cornelia , Becker Alexandra S. , Ho Anthony D. , Tanaka Motomu
Published: July 2018

We studied the dynamic behavior of human hematopoietic stem cells (HSC) on the in vitro model of bone marrow surfaces in the absence and presence of chemokine (SDF1α). The deformation and migration of cells were investigated by varying the chemokine concentration and surface density of ligand molecules. Since HSC used in this study were primary cells extracted from the human umbilical cord blood, it is not possible to introduce molecular reporter systems before or during the live cell imaging. To account for the experimental observations, we propose a simple and general theoretical model for cell crawling. In contrast to other theoretical models reported previously, our model focuses on the nonlinear coupling between shape deformation and translational motion and is free from any molecular-level process. Therefore, it is ideally suited for the comparison with our experimental results. We have demonstrated that the results in the absence of SDF1α were well recapitulated by the linear model, while the nonlinear model is necessary to reproduce the elongated migration observed in the presence of SDF1α. The combination of the simple theoretical model and the label-free, live cell observations of human primary cells opens a large potential to numerically identify the differential effects of extrinsic factors such as chemokines, growth factors, and clinical drugs on dynamic phenotypes of primary cells.
The Drosophila microbiome has a limited influence on sleep, activity, and courtship behaviors
Authors: Selkrig Joel , Mohammad Farhan , Ng Soon Hwee , Chua Jia Yi , Tumkaya Tayfun , Ho Joses , Chiang Yin Ning , Rieger Dirk , Pettersson Sven , Helfrich-Förster Charlotte , Yew Joanne Y. , Claridge-Chang Adam
Published: July 2018

In animals, commensal microbes modulate various physiological functions, including behavior. While microbiota exposure is required for normal behavior in mammals, it is not known how widely this dependency is present in other animal species. We proposed the hypothesis that the microbiome has a major influence on the behavior of the vinegar fly (Drosophila melanogaster), a major invertebrate model organism. Several assays were used to test the contribution of the microbiome on some well-characterized behaviors: defensive behavior, sleep, locomotion, and courtship in microbe-bearing, control flies and two generations of germ-free animals. None of the behaviors were largely influenced by the absence of a microbiome, and the small or moderate effects were not generalizable between replicates and/or generations. These results refute the hypothesis, indicating that the Drosophila microbiome does not have a major influence over several behaviors fundamental to the animal’s survival and reproduction. The impact of commensal microbes on animal behaviour may not be broadly conserved.