bluuebunny/crossref_metadata_2025 huggingface dataset:
The Revolutionary Democracy of Ethiopia: A Wartime Ideology Both Shaping and Shaped by Peacetime Policy Needs
Authors: Aalen Lovise
Published: February 2019

The Ethiopian People’s Revolutionary Democratic Front (EPRDF), victor in the civil war in 1991, has since transformed into an authoritarian party. While this transition is well covered in the literature, few studies have explored how the party’s ideology has adapted after its position was consolidated. This article addresses this gap, by analysing the EPRDF’s ideology of revolutionary democracy, and how the interpretation of it has changed over time. The Ethiopian case shows that wartime ideologies should not be considered as static remnants of the past. Instead, the ideology has served as a flexible political tool for controlling the state and for justifying or concealing major policy changes. More recent protests and ruptures in the ruling party, however, indicate that revolutionary democracy may have an expiry date. There seems thus to be a limit to how long a wartime ideology can provide power to uphold a rebel government’s hegemony and coherence.
Laminar spread of a circular liquid jet impinging axially on a rotating disc
Authors: Scheichl B. , Kluwick A.
Published: February 2019

The steady laminar annular spread of a thin liquid film generated by a circular jet which impinges perpendicularly in direction of gravity on the centre of a rotating disc is examined both analytically and numerically. Matched asymptotic expansions of the flow quantities provide the proper means for studying the individual flow regimes arising due to the largeness of the Reynolds number formed with the radius of the jet, its slenderness and the relative magnitude of the centrifugal body force. This is measured by a suitably defined Rossby number,$Ro$. The careful analysis of jet impingement predicts a marked influence of gravity and surface tension on the film flow, considered in the spirit of a shallow-water approach, only through the vorticity imposed by the jet flow. Accordingly, associated downstream conditions are disregarded as the local Froude and Weber numbers are taken to be sufficiently large. Hence, the parabolic problem shaped from the governing equations in a rigorous manner describes the strongly supercritical spread of a developed viscous film past an infinite disc, essentially controlled by$Ro$. Its numerical solutions are discussed for a wide range of values of$Ro$. The different flow regimes reflecting varying effects of viscous shear and centrifugal force are elucidated systematically to clarify the surprising richness of flow phenomena. Special attention is paid to the cases$Ro\gg 1$and$Ro\ll 1$. The latter, referring to relatively high disc spin, implies a delicate breakdown of the asymptotic flow structure, thus requiring a specific analytical and numerical treatment. Finally, the impact of gravity and capillarity and thus of the disc edge on the film flow is envisaged in brief.
Identifying disruptions to the ecological balance of nature: a foraminiferal example across the initiation of the Paleocene–Eocene thermal maximum
Authors: Hayek Lee-Ann C. , Buzas Martin A. , Thomas Ellen
Published: February 2019

Deriving ecological and evolutionary descriptions of, and implications from, faunal assemblage patterns is commonly addressed by observation and a variety of exploratory techniques (scaling and clustering), along with qualitative evaluations of species occurrences and relative abundances. We argue that interpretations of faunal patterns, especially those documented by the fossil record, should be based upon the composition and structure of entire communities to provide strong conclusions and replicable results.

As an example, we use benthic foraminiferal data at high resolution (1–2 cm, corresponding to 300–1400 yr) over a section corresponding to about 20 kyr across the beginning of the Paleocene–Eocene thermal maximum (PETM). The PETM was an episode of rapid global warming about 55.5 Ma, associated with ocean acidification and lowered open oceanic productivity and deoxygenation and marked by severe turnover in benthic foraminiferal assemblages. Here we provide a stand-alone approach applicable to any dynamic faunal system, perturbation detection analysis (PDA), to recognize and identify community disruption evidenced as either positive growth or negative decline, and we use this methodical approach to obtain new information on foraminiferal communities before, during, and after the initiation of the PETM.

We conclude that the late Paleocene benthic foraminiferal community (FCOM1) was in a growth stage of positive increasing diversity, suggestive of favorable environmental conditions. This stage continued through the initial changes at the onset of the PETM, when disruption through environmental stress led to this community's termination. A second community (FCOM2) formed with declining diversity and high variability, showing a lack of adaptation to changing conditions. Knowledge of total assemblage status under both adverse and advantageous conditions is necessary, but not recognized by methods that rely upon analysis of single samples only: individual samples cannot be used to recognize disruptive changes in a community's structure, but these are easily identified using PDA.
ORIENTED FLIP GRAPHS, NONCROSSING TREE PARTITIONS, AND REPRESENTATION THEORY OF TILING ALGEBRAS
Authors: GARVER ALEXANDER , MCCONVILLE THOMAS
Published: February 2019

The purpose of this paper is to understand lattices of certain subcategories in module categories of representation-finite gentle algebras called tiling algebras, as introduced by Coelho Simões and Parsons. We present combinatorial models for torsion pairs and wide subcategories in the module category of tiling algebras. Our models use the oriented flip graphs and noncrossing tree partitions, previously introduced by the authors, and a description of the extension spaces between indecomposable modules over tiling algebras. In addition, we classify two-term simple-minded collections in bounded derived categories of tiling algebras. As a consequence, we obtain a characterization ofc-matrices for any quiver mutation-equivalent to a typeADynkin quiver.
Political Activism and Firm Innovation
Authors: Ovtchinnikov Alexei V. , Reza Syed Walid , Wu Yanhui
Published: February 2019

We hypothesize that political activism is valuable because it helps reduce political uncertainty, which, in turn, fosters firm innovation. We find that firms that support more politicians, winning politicians, politicians on congressional committees with jurisdictional authority over the firms’ industries, and politicians who join those committees innovate more. We employ a natural experiment to show a causal effect of political activism on innovation. We also show evidence of intra-industry and geographical political activism spillovers.
The Permafrost Young Researchers Network (PYRN) is getting older: The past, present, and future of our evolving community
Authors: Tanski George , Bergstedt Helena , Bevington Alexandre , Bonnaventure Philip , Bouchard Frédéric , Coch Caroline , Dumais Simon , Evgrafova Alevtina , Frauenfeld Oliver W. , Frederick Jennifer , Fritz Michael , Frolov Denis , Harder Silvie , Hartmeyer Ingo , Heslop Joanne , Högström Elin , Johansson Margareta , Kraev Gleb , Kuznetsova Elena , Lenz Josefine , Lupachev Alexey , Magnin Florence , Martens Jannik , Maslakov Alexey , Morgenstern Anne , Nieuwendam Alexandre , Oliva Marc , Radosavljevic Boris , Ramage Justine , Schneider Andrea , Stanilovskaya Julia , Strauss Jens , Trochim Erin , Vecellio Daniel J. , Weber Samuel , Lantuit Hugues
Published: February 2019

A lasting legacy of the International Polar Year (IPY) 2007–2008 was the promotion of the Permafrost Young Researchers Network (PYRN), initially an IPY outreach and education activity by the International Permafrost Association (IPA). With the momentum of IPY, PYRN developed into a thriving network that still connects young permafrost scientists, engineers, and researchers from other disciplines. This research note summarises (1) PYRN’s development since 2005 and the IPY’s role, (2) the first 2015 PYRN census and survey results, and (3) PYRN’s future plans to improve international and interdisciplinary exchange between young researchers. The review concludes that PYRN is an established network within the polar research community that has continually developed since 2005. PYRN’s successful activities were largely fostered by IPY. With >200 of the 1200 registered members active and engaged, PYRN is capitalising on the availability of social media tools and rising to meet environmental challenges while maintaining its role as a successful network honouring the legacy of IPY.
EDUCATIONAL DISPARITIES IN COLOMBIA 1904-58: NEW EVIDENCE FROM A REGIONAL LEVEL APPROACH
Authors: Fuentes-Vásquez María José
Published: February 2019

Regional economic differences in Colombia have persisted over time. The present study seeks to contribute to the debate on the territorial differences of the country through the identification of patterns of low coverage in both primary and secondary education between 1904 and 1958. The results, coinciding with other studies on income, show a tendency towards the formation of an educational cluster in the centre of the country and the existence of a human capital trap in the periphery. The results also suggest that there is a high correlation between fiscal capacity and enrolment rates. Finally, it can also be observed that territories with the highest enrolment rates are associated with high urban enrolment rates during the process of country-wide urbanisation.
THE DEVELOPMENT OF SELF-DETERMINATION ACROSS THE LANGUAGE COURSE
Authors: Noels Kimberly A. , Vargas Lascano Dayuma I. , Saumure Kristie
Published: February 2019

Research suggests that students put more effort into language learning when they feel that it is a voluntary and self-relevant activity or they enjoy the process of mastering that language (i.e., they have a more self-determined orientation). This orientation is fostered when learners feel autonomous, competent, and related to others in their learning environment. We followed 162 university students of French across one semester to examine these causal claims longitudinally. Latent growth curve modeling showed that feelings of autonomy, competence, and relatedness and self-determined motivation increased across the semester while engagement declined. Parallel processes growth curve modeling showed that declines in engagement across the semester were attenuated to the extent that self-determined motivation increased. Auto-regressive cross-lagged analysis showed that, contrary to expectation, more engagement as the semester started predicted greater self-determination mid-semester (instead of vice versa), but these relations became reciprocal from mid-semester on. These findings are consistent with a dynamic model of motivation that emphasizes the reciprocal interplay between motivational constructs over the duration of a language course. The implications of these findings for motivation theory and instructional practices are discussed.
Mining for humanity in the deep sea and outer space: The role of small states and international law in the extraterritorial expansion of extraction
Authors: Feichtner Isabel
Published: February 2019

This article explores how Luxembourg and Nauru put their sovereignty to use in order to become global players in what can be considered extraterritorial landgrabs – the turning of the deep seabed and outer space into realms of commercial exploitation. It shows how the international legal framework puts states, however small, into a position to facilitate private enterprises’ endeavours to obtain extraterritorial exploitation rights. The article further enquires into the public interest justifications put forward by governments to legitimate their support for the expansion of private resource extraction into the deep sea and outer space. It finds that these justifications are very tenuous; that governments refer to vague notions of economic growth and benefits that may accrue from extraction to an undefined humanity while it remains unclear whether their own populations will obtain any concrete gains. Both case studies illustrate how states, on the basis of international law, facilitate the expansion of private value extraction, thus perverting the redistributive ambitions that may once have motivated the negotiations of the United Nations Convention on the Law of the Sea and the Outer Space Treaty.
Returning foreign fighters: The case of Denmark
Authors: Jakobsen Helene Højfeldt
Published: February 2019

This article considers which legal regimes apply in cases where a Danish citizen and/or resident returns from Syria or Iraq after having taken part in the armed conflict on behalf of the group known as Islamic State, and continues his/her affiliation with the armed group. The article argues that international humanitarian law currently applies to the Danish territory and that a Danish foreign fighter may continue to be considered as taking a direct part in hostilities after having returned from Iraq or Syria. The article then considers the application of Danish criminal law to returned foreign fighters and argues that Danish counterterrorism laws do not apply to members of the armed forces of an armed group that is party to an armed conflict with Denmark.
Using Instagram While “In a Relationship”
Authors: Lee Eunji , Choi Tae Rang , Lee Taejun (David) , Sung Yongjun
Published: February 2019

Abstract. Despite the continued attention on the distinct behavioral and relational outcomes of narcissism and self-esteem, limited academic research has been devoted to investigating the influences of those individual differences upon behaviors of seeking and retaining a romantic relationship concurrently in the digital environment. The present study aimed to test the role that narcissism and self-esteem play in predicting individuals’ attitudes toward behaviors in current and possible romantic relationships. The results demonstrated that individuals high in narcissism showed positive attitudes toward interacting with potential romantic partners on Instagram. Furthermore, they showed positive attitudes toward current relationship-related postings on Instagram. In contrast, individuals high in self-esteem exhibited negative attitudes toward interacting with potential romantic partners, whereas they showed positive attitudes toward posting photographs taken with their current romantic partners on Instagram. This study provides empirical evidence for the associations between individual differences and attitudes toward various behaviors on social networking sites (SNSs) in relation to both potential and current romantic relationships.
Unraveling the Mystery of Indian Summer Monsoon Prediction: Improved Estimate of Predictability Limit
Authors: Saha Subodh Kumar , Hazra Anupam , Pokhrel Samir , Chaudhari Hemantkumar S. , Sujith K. , Rai Archana , Rahaman Hasibur , Goswami B. N.
Published: February 2019

Large socioeconomic impact of the Indian summer monsoon (ISM) extremes motivated numerous attempts at its long range prediction over the past century. However, a rather low potential predictability (PP) of the seasonal ISM, contributed significantly by “internal,” interannual variability was considered insurmountable. Here we show that the internal variability contributed by the ISM subseasonal (synoptic + intraseasonal) fluctuations, so far considered chaotic, is partly predictable as found to be tied to slowly varying forcing (e.g., El Niño and Southern Oscillation). This provides a scientific basis for predictability of the ISM rainfall beyond the conventional estimates of PP. We establish a much higher actual limit of PP (r∼0.82) through an extensive reforecast experiment (1,920 years of simulation) by improving two major physics in a global coupled climate model, which raises a hope for a very reliable dynamical seasonal ISM forecasting in the near future.
Prediction of Ice‐Free Conditions for a Perennially Ice‐Covered Antarctic Lake
Authors: Obryk M. K. , Doran P. T. , Priscu J. C.
Published: February 2019

Although perennially ice‐covered Antarctic lakes have experienced variable ice thicknesses over the past several decades, future ice thickness trends and associated aquatic biological responses under projected global warming remain unknown. Heat stored in the water column in chemically stratified Antarctic lakes that have middepth temperature maxima can significantly influence the ice thickness trends via upward heat flux to the ice/water interface. We modeled the ice thickness of the west lobe of Lake Bonney, Antarctica, based on possible future climate scenarios utilizing a 1D thermodynamic model that accounts for surface radiative fluxes as well as the heat flux associated with the temperature evolution of the water column. Model results predict that the ice cover of Lake Bonney will shift from perennial to seasonal within one to four decades, a change that will drastically influence ecosystem processes within the lake.
Gut microbiota community characteristics and disease-related microorganism pattern in a population of healthy Chinese people
Authors: Zhang Wen , Li Juan , Lu Shan , Han Na , Miao Jiaojiao , Zhang Tingting , Qiang Yujun , Kong Yanhua , Wang Hong , Gao Tongxin , Liu Yuqing , Li Xiuwen , Peng Xianhui , Chen Xia , Zhao Xiaofei , Che Jie , Zhang Ling , Chen Xi , Zhang Qing , Hu Ming , Li Qun , Kan Biao
Published: February 2019

China’s population accounts for about 1/5th of the world’s total population. Owing to differences in environment, race, living habits, and other factors, the structure of the intestinal flora of Chinese individuals is expected to have unique features; however, this has not been thoroughly examined. Here, we collected faecal samples from healthy adults living in three cities of China and investigated their gut microbiome using metagenomics and bioinformatics technology. We found that 11 core bacterial genera were present in all of the Chinese faecal samples; moreover, several patient characteristics (age, region, body mass index, physical exercise, smoking habits, and alcoholic drink, and yogurt consumption) were found to have different effects on the gut microbiome of healthy Chinese people. We also examined the distribution patterns of disease-related microorganisms (DRMs), revealing which DRMs can potentially be used as markers for assessment of health risk. We also developed a program called “Guthealthy” for evaluating the health status associated with the microbiome and DRM pattern in the faecal samples. The microbiota data obtained in this study will provide a basis for a healthy gut microbiome composition in the Chinese population.
Epigenetic mechanisms mediate the experimental evolution of resistance against parasitic fungi in the greater wax moth Galleria mellonella
Authors: Mukherjee Krishnendu , Dubovskiy Ivan , Grizanova Ekaterina , Lehmann Rüdiger , Vilcinskas Andreas
Published: February 2019

Recent concepts in evolutionary biology suggest that epigenetic mechanisms can translate environmental selection pressures into heritable changes in phenotype. To determine whether experimental selection for a complex trait in insects involves epigenetic modifications, we carried out a generation-spanning experiment using larvae of the greater wax moth Galleria mellonella as a model host to investigate the role of epigenetics in the heritability of resistance against the parasitic fungus Metarhizium robertsii. We investigated differences in DNA methylation, histone acetylation and microRNA (miRNA) expression between an experimentally resistant population and an unselected, susceptible line, revealing that the survival of G. mellonella larvae infected with M. robertsii correlates with tissue-specific changes in DNA methylation and histone modification and the modulation of genes encoding the corresponding enzymes. We also identified miRNAs differentially expressed between resistant and susceptible larvae and showed that these regulatory molecules target genes encoding proteinases and proteinase inhibitors, as well as genes related to cuticle composition, innate immunity and metabolism. These results support our hypothesis that epigenetic mechanisms facilitate, at least in part, the heritable manifestation of parasite resistance in insects. The reciprocal adaptations underlying host–parasite coevolution therefore extend beyond the genetic level to encompass epigenetic modifications.
Scouting for Naturally Low-Toxicity Wheat Genotypes by a Multidisciplinary Approach
Authors: Pilolli Rosa , Gadaleta Agata , Mamone Gianfranco , Nigro Domenica , De Angelis Elisabetta , Montemurro Nicola , Monaci Linda
Published: February 2019

Over the last years, great efforts have been devoted to develop effective gluten detoxification strategies with a consequent detrimental alteration of the technological properties as well. Obtaining low-gluten products without affecting the rheological properties of wheat could still be considered a new challenge to face. In this investigation, we presented a comprehensive characterization of durum wheat genotypes aimed at identifying low gluten ones, which combine the potential lower toxicity/immunogenicity with conserved yield and rheological properties to encompass the perspective usability for bread or pasta making. A preliminary profiling of gluten proteins was accomplished by immunoassay-based quantification and liquid chromatography coupled to UV detection, focusing on the gliadin fraction as main responsible for immunoreactivity in celiac disease patients. In addition, data on grain protein content, grain yield per spike, dry gluten and gluten index were collected in order to provide complementary information about productivity-related traits and quali-quantitative characteristics related to wheat nutritional value and its technological properties. The whole pool of data was statistically evaluated driving to the selection of a preferred list of candidate low-toxicity genotypes that were subjected to in-vitro simulated gastroduodenal digestion and untargeted HR-MS/MS peptide identification. Finally, an in-silico risk assessment of potential toxicity for celiac disease patients was performed according to the most recent guidance provided by EFSA.
Chronic olanzapine administration causes metabolic syndrome through inflammatory cytokines in rodent models of insulin resistance
Authors: Li Huqun , Peng Shiyong , Li Shihong , Liu Shouqing , Lv Yifan , Yang Ni , Yu Liangyu , Deng Ya-Hui , Zhang Zhongjian , Fang Maosheng , Huo Yunxiang , Chen Ying , Sun Taohua , Li Weiyong
Published: February 2019

Olanzapine is a second-generation anti-psychotic drug used to prevent neuroinflammation in patients with schizophrenia. However, the long-term administration of olanzapine leads to insulin resistance (IR); the mechanisms of this effect remains poorly understood. Using cellular and rodent models of IR induced by olanzapine, we found that chronic olanzapine treatment induces differential inflammatory cytokine reactions in peripheral adipose and the central nervous system. Long-term treatment of olanzapine caused metabolic symptoms, including IR, by markedly elevating the plasma levels of pro-inflammatory cytokines, including IL-1ß, IL-6, IL-8 and TNFα; these findings are consistent with observations from schizophrenia patients chronically treated with olanzapine. Our observations of differential inflammatory cytokine responses in white adipose tissues from the prefrontal cortex in the brain indicated cell type-specific effects of the drug. These cytokines induced IR by activating NF-kB through the suppression of IkBα. Functional blockade of the components p50/p65 of NF-kB rescued olanzapine-induced IR in NIH-3T3 L1-derived adipocytes. Our findings demonstrate that olanzapine induces inflammatory cytokine reactions in peripheral tissues without adversely affecting the central nervous system and suggest that chronic olanzapine treatment of schizophrenia patients may cause inflammation-mediated IR with minimal or no adverse effects in the brain.
PFDB: A standardized protein folding database with temperature correction
Authors: Manavalan Balachandran , Kuwajima Kunihiro , Lee Jooyoung
Published: February 2019

We constructed a standardized protein folding kinetics database (PFDB) in which the logarithmic rate constants of all listed proteins are calculated at the standard temperature (25 °C). A temperature correction based on the Eyring–Kramers equation was introduced for proteins whose folding kinetics were originally measured at temperatures other than 25 °C. We verified the temperature correction by comparing the logarithmic rate constants predicted and experimentally observed at 25 °C for 14 different proteins, and the results demonstrated improvement of the quality of the database. PFDB consists of 141 (89 two-state and 52 non-two-state) single-domain globular proteins, which has the largest number among the currently available databases of protein folding kinetics. PFDB is thus intended to be used as a standard for developing and testing future predictive and theoretical studies of protein folding. PFDB can be accessed from the following link: http://lee.kias.re.kr/~bala/PFDB.
Evaluation of cationic channel TRPV2 as a novel biomarker and therapeutic target in Leukemia-Implications concerning the resolution of pulmonary inflammation
Authors: Siveen Kodappully S. , Prabhu Kirti S. , Parray Aeijaz S. , Merhi Maysaloun , Arredouani Abdelilah , Chikri Mohamed , Uddin Shahab , Dermime Said , Mohammad Ramzi M. , Steinhoff Martin , Janahi Ibrahim A. , Azizi Fouad
Published: February 2019

Patients treated during leukemia face the risk of complications including pulmonary dysfunction that may result from infiltration of leukemic blast cells (LBCs) into lung parenchyma and interstitium. In LBCs, we demonstrated that transient receptor potential vanilloid type 2 channel (TRPV2), reputed for its role in inflammatory processes, exhibited oncogenic activity associated with alteration of its molecular expression profile. TRPV2 was overexpressed in LBCs compared to normal human peripheral blood mononuclear cells (PBMCs). Additionally, functional full length isoform and nonfunctional short form pore-less variant of TRPV2 protein were up-regulated and down-regulated respectively in LBCs. However, the opposite was found in PBMCs. TRPV2 silencing or pharmacological targeting by Tranilast (TL) or SKF96365 (SKF) triggered caspace-mediated apoptosis and cell cycle arrest. TL and SKF inhibited chemotactic peptide fMLP-induced response linked to TRPV2 Ca2+ activity, and down-regulated expression of surface marker CD38 involved in leukemia and lung airway inflammation. Challenging lung airway epithelial cells (AECs) with LBCs decreased (by more than 50%) transepithelial resistance (TER) denoting barrier function alteration. Importantly, TL prevented such loss in TER. Therefore, TRPV2 merits further exploration as a pharmacodynamic biomarker for leukemia patients (with pulmonary inflammation) who might be suitable for a novel [adjuvant] therapeutic strategy based on TL.
Fast NMR method to probe solvent accessibility and disordered regions in proteins
Authors: Faustino André F. , Barbosa Glauce M. , Silva Micael , Castanho Miguel A. R. B. , Da Poian Andrea T. , Cabrita Eurico J. , Santos Nuno C. , Almeida Fabio C. L. , Martins Ivo C.
Published: February 2019

Understanding protein structure and dynamics, which govern key cellular processes, is crucial for basic and applied research. Intrinsically disordered protein (IDP) regions display multifunctionality via alternative transient conformations, being key players in disease mechanisms. IDP regions are abundant, namely in small viruses, allowing a large number of functions out of a small proteome. The relation between protein function and structure is thus now seen from a different perspective: as IDP regions enable transient structural arrangements, each conformer can play different roles within the cell. However, as IDP regions are hard and time-consuming to study via classical techniques (optimized for globular proteins with unique conformations), new methods are required. Here, employing the dengue virus (DENV) capsid (C) protein and the immunoglobulin-binding domain of streptococcal protein G, we describe a straightforward NMR method to differentiate the solvent accessibility of single amino acid N-H groups in structured and IDP regions. We also gain insights into DENV C flexible fold region biological activity. The method, based on minimal pH changes, uses the well-established 1H-15N HSQC pulse sequence and is easily implementable in current protein NMR routines. The data generated are simple to interpret, with this rapid approach being an useful first-choice IDPs characterization method.
Bioinformatic discovery of a toxin family in Chryseobacterium piperi with sequence similarity to botulinum neurotoxins
Authors: Mansfield Michael James , Wentz Travis Gwynn , Zhang Sicai , Lee Elliot Jeon , Dong Min , Sharma Shashi Kant , Doxey Andrew Charles
Published: February 2019

Clostridial neurotoxins (CNTs), which include botulinum neurotoxins (BoNTs) and tetanus neurotoxin (TeNT), are the most potent toxins known to science and are the causative agents of botulism and tetanus, respectively. The evolutionary origins of CNTs and their relationships to other proteins remains an intriguing question. Here we present a large-scale bioinformatic screen for putative toxin genes in all currently available genomes. We detect a total of 311 protein sequences displaying at least partial homology to BoNTs, including 161 predicted toxin sequences that have never been characterized. We focus on a novel toxin family from Chryseobacterium piperi with homology to BoNTs. We resequenced the genome of C. piperi to confirm and further analyze the genomic context of these toxins, and also examined their potential toxicity by expression of the protease domain of one C. piperi toxin in human cells. Our analysis suggests that these C. piperi sequences encode a novel family of metalloprotease toxins that are distantly related to BoNTs with similar domain architecture. These toxins target a yet unknown class of substrates, potentially reflecting divergence in substrate specificity between the metalloprotease domains of these toxins and the related metalloprotease domain of clostridial neurotoxins.
Exciton binding energy and hydrogenic Rydberg series in layered ReS2
Authors: Jadczak J. , Kutrowska-Girzycka J. , Smoleński T. , Kossacki P. , Huang Y. S. , Bryja L.
Published: February 2019

Unlike monolayers of transition metal dichalcogenides such as MoS2,which possess high in-plane symmetry, layered ReS2exhibits reduced in-plane crystal symmetry with a distorted 1 T structure. This unique symmetry leads to anisotropic optical properties, very promising for light polarization devices. Here, we report on low temperature polarization-resolved emission and absorption measurements of excitons in ReS2from bulk to monolayer. In photoluminescence and reflectivity contrast spectra we distinguish two strongly polarized excitons X1and X2with dipole vectors along different crystal directions, which persist from bulk down to monolayer. Basing on the PL and RC spectra of bulk crystals we determine the energy of the ground and first four excited states of both excitons, which follow the usual hydrogenic Rydberg series of energy levels of 3D excitonic states (En = Ry*/n2). From the numerical fit we estimate that the energy gap is direct and equal to 1671.7 meV and binding energy of X1and X2is equal to 117.5 and 86.6 meV, respectively. In magneto-PL spectra of bulk ReS2up to B = 10 T, the energy shift of all the states is below 2 meV. On reducing the crystal thickness from bulk to monolayer the ground state experience a strong blue shift.
Gas chromatography-Mass Spectra analysis and deleterious potential of fungal based polythene-degradation products
Authors: Sangale Manisha K. , Shahnawaz Mohd. , Ade Avinash B.
Published: February 2019

Polythene-degradation products (PE-DPs) produced due to two most efficient polythene degrading fungal isolates (Aspergillus terreus strain MANF1/WL and Aspergillus sydowii strain PNPF15/TS) after 60 days of incubation at ambient temperature with continuous shaking were analyzed by employing GC-MS method. Total 24 PE-DPs were recorded in total 4 samples i) control (pH 3.5), ii) Treatment of Aspergillus terreus strain MANF1/WL (pH 3.5), iii) control (pH 9.5) and iv) Treatment of Aspergillus sydowii strain PNP15/TS (pH 9.5). To check the deleterious status of PE-DPs using both the elite fungal isolates at in vitro level, two living systems (Sorghum and Tiger shark) were used. The percent germination rate of sorghum seeds were found unaffected with PE-DPs of both elite fungi. PE-DPs of both the fungal isolates exhibited maximum germination index at 50%. Whereas, highest elongation inhibition rate (34.75 ± 7.10) was reported with PE-DPs of Aspergillus terreus strain MANF1/WL. In case of animals system, no mortality of the Tiger sharks was documented after fifteen days of the treatment.
Disentangling locus of perceptual learning in the visual hierarchy of motion processing
Authors: Zhang Ruyuan , Tadin Duje
Published: February 2019

Visual perceptual learning (VPL) can lead to long-lasting perceptual improvements. One of the central topics in VPL studies is the locus of plasticity in the visual processing hierarchy. Here, we tackled this question in the context of motion processing. We took advantage of an established transition from component-dependent representations at the earliest level to pattern-dependent representations at the middle-level of cortical motion processing. Two groups of participants were trained on the same motion direction identification task using either grating or plaid stimuli. A set of pre- and post-training tests was used to determine the degree of learning specificity and generalizability. This approach allowed us to disentangle contributions from different levels of processing stages to behavioral improvements. We observed a complete bi-directional transfer of learning between component and pattern stimuli that moved to the same directions, indicating learning-induced plasticity associated with intermediate levels of motion processing. Moreover, we found that motion VPL is specific to the trained stimulus direction, speed, size, and contrast, diminishing the possibility of non-sensory decision-level enhancements. Taken together, these results indicate that, at least for the type of stimuli and the task used here, motion VPL most likely alters visual computation associated with signals at the middle stage of motion processing.
The Flashed Face Distortion Effect Does Not Depend on Face-Specific Mechanisms
Authors: Balas Benjamin , Pearson Hannah
Published: February 2019

When normal faces are rapidly presented in the visual periphery, they are perceived as grotesque and distorted. This phenomenon, “The flashed-face distortion effect” (FFDE) is a powerful illusion that may reveal important properties of how faces are coded in peripheral vision. Despite the strength of the illusion (and its popularity), there has been almost no follow-up work to examine what governs the strength of the illusion or to develop a clear account of its phenomenology. Presently, our goal was to address this by manipulating aspects of facial appearance and spatial/temporal properties of the flashed-face stimulus to determine what factors modulate the illusion’s strength. In three experiments, we investigated the extent to which local contrast (operationalized by the presence or absence of makeup), image eccentricity, image size, face inversion, and presentation rate of images within the sequence each contributed to the strength of the FFDE. We found that some of these factors (eccentricity and presentation rate) mattered a great deal, while others (makeup, face inversion and image size) made little contribution to the strength of the FFDE. We discuss the implications of these results for a mechanistic account of the FFDE, and suggest several avenues for future research based on this compelling visual illusion.
Serum concentrations of IGF-I/IGF-II as biomarkers of alcohol damage during foetal development and diagnostic markers of Foetal Alcohol Syndrome
Authors: Andreu-Fernández Vicente , Bastons-Compta Adriana , Navarro-Tapia Elisabet , Sailer Sebastian , Garcia-Algar Oscar
Published: February 2019

Foetal Alcohol Syndrome (FAS) is the most deleterious health effect derived from alcohol consumption during pregnancy and is placed at the end of the Foetal Alcohol Spectrum Disorders (FASD). Few studies have proposed potential molecular biomarkers of physical and neurological damage associated with prenatal alcohol exposure. We prospectively recruited 55 children from 8 to 12 years old, with a prenatal assessment for ethanol exposure using meconium analysis of fatty acid ethyl esters (FAEE). The control group was established for FAEE < 2 nmol/g (n = 31) and a Prenatal Ethanol Exposure (PEE) group for FAEEs > 2 nmol/g (n = 33). Moreover, 98 children adopted from Eastern European Countries (EEC) were also recruited to evaluate FASD diagnosis comprising 31 cases with complete FAS, 42 with partial FAS, 6 with ARBD and 5 with ARND. Serum values of IGF-I and IGF-II for all children recruited were determined by immunoassay. Anthropometric and neurocognitive evaluation showed severe impairments in FAS children, moderate effects in PEE and no harmful effects in the control group with no prenatal exposure to alcohol. Analysis of IGF-I and IGF-II serum concentrations revealed that FASD from EEC as well as PEE children showed significantly lower concentrations of both IGF-I and IFG-II than the control group and reference values. Moreover, Spearman correlations showed a significant effect of IGF-I on anthropometric measurements in girls, whereas IGF-II affected the neuropsychological variables in both genders. These findings validate the use of growth factors IGF-I and IGF-II as surrogate biomarkers of damage induced by prenatal exposure to ethanol and could be used in the diagnosis of foetal alcohol spectrum disorders.
Activator of G-protein signaling 8 is involved in VEGF-induced choroidal neovascularization
Authors: Hayashi Hisaki , Mamun Abdullah Al , Takeyama Masayuki , Yamamura Aya , Zako Masahiro , Yagasaki Rina , Nakahara Tsutomu , Kamei Motohiro , Sato Motohiko
Published: February 2019

Choroidal neovascularization (CNV) is associated with age-related macular degeneration (AMD), a major cause of vision loss among elderly people. Vascular endothelial cell growth factor (VEGF) is essential for the development and progression of AMD, and VEGF signaling molecules are effective targets for the treatment of AMD. We recently reported that activator of G-protein signaling 8 (AGS8), a receptor-independent Gβγ regulator, is involved in VEGF-induced angiogenesis in cultured endothelial cells (EC); however, the role of AGS8 in CNV is not yet understood. This study aimed to explore the role of AGS8 in CNV in cultured cells, explanted choroid tissue, and laser-induced CNV in a mouse AMD model. AGS8 knockdown in cultured choroidal EC inhibited VEGF-induced VEGFR-2 phosphorylation, cell proliferation, and migration. AGS8 knockdown also downregulated cell sprouting from mouse choroidal tissue in ex vivo culture. A mouse model of laser-induced CNV, created to analyze the roles of AGS8 in vivo, demonstrated that AGS8 mRNA was significantly upregulated in choroidal lesions and AGS8 was specifically expressed in the neovasculature. Local AGS8 knockdown in intravitreal tissue significantly inhibited laser-induced AGS8 upregulation and suppressed CNV, suggesting that AGS8 knockdown in the choroid has therapeutic potential for AMD. Together, these results demonstrate that AGS8 plays critical roles in VEGF-induced CNV.
Application of Latent Class Analysis to Identify Metabolic Syndrome Components Patterns in adults: Tehran Lipid and Glucose study
Authors: Ahanchi Noushin Sadat , Hadaegh Farzad , Alipour Abbas , Ghanbarian Arash , Azizi Fereidoun , Khalili Davood
Published: February 2019

In this study, using latent class analysis (LCA), we investigated whether there are any homogeneous subclasses of individuals exhibiting different profiles of metabolic syndrome (MetS) components. The current study was conducted within the framework of the Tehran Lipid and Glucose Study (TLGS), a population-based cohort including 6448 subjects, aged 20–50 years. We carried out a LCA on MetS components and assessed the association of some demographic and behavioral variables with membership of latent subclasses using multinomial logistic regression. Four latent classes were identified:(1) Low riskclass, with the lowest probabilities for all MetS components (its prevalence rate in men: 29%, women: 64.7%), (2) MetS with diabetes medication (men: 1%, women: 2.3%), (3) Mets without diabetes medication (men: 32%, women: 13.4%), (4) dyslipidemia (men: 38%, women: 19.6%). In men the forth subclass was more significantly associated with being smoker (odds ratio: 4.49; 95% CI: 1.89–9.97). Our study showed that subjects with MetS could be classified in sub-classes with different origins for their metabolic disorders including drug treated diabetes, those with central obesity and dyslipidemia associated with smoking.
Voluntary running rescues the defective hippocampal neurogenesis and behaviour observed in lipocalin 2-null mice
Authors: Ferreira Ana Catarina , Novais Ashley , Sousa Nuno , Sousa João Carlos , Marques Fernanda
Published: February 2019

The continuous generation of new neurons in the adult mammalian hippocampus is a form of neural plasticity that modulates learning and memory functions, and also emotion (anxiety and depression). Among the factors known to modulate adult hippocampal neurogenesis and brain function, lipocalin-2 (LCN2) was recently described as a key regulator of neural stem cells (NSCs) proliferation and commitment, with impact on several dimensions of behaviour. Herein, we evaluated whether voluntary running, a well-known regulator of cell genesis, rescue the deficient adult hippocampal neurogenesis observed in mice lacking LCN2. We observed that running, by counteracting oxidative stress in NSCs, reverses LCN2-null mice defective hippocampal neurogenesis, as it promotes NSCs cell cycle progression and maturation, resulting in a partial reduction in anxiety and improved contextual behaviour. Together, these findings demonstrate that running is a positive modulator of adult hippocampal neurogenesis and behaviour in mice lacking LCN2, by impacting on the antioxidant kinetics of NSCs.
Enabling precision medicine by unravelling disease pathophysiology: quantifying signal transduction pathway activity across cell and tissue types
Authors: van de Stolpe Anja , Holtzer Laurent , van Ooijen Henk , Inda Marcia Alves de , Verhaegh Wim
Published: February 2019

Signal transduction pathways are important in physiology and pathophysiology. Targeted drugs aim at modifying pathogenic pathway activity, e.g., in cancer. Optimal treatment choice requires assays to measure pathway activity in individual patient tissue or cell samples. We developed a method enabling quantitative measurement of functional pathway activity based on Bayesian computational model inference of pathway activity from measurements of mRNA levels of target genes of the pathway-associated transcription factor. Oestrogen receptor, Wnt, and PI3K-FOXO pathway assays have been described previously. Here, we report model development for androgen receptor, Hedgehog, TGFβ, and NFκB pathway assays, biological validation on multiple cell types, and analysis of data from published clinical studies (multiple sclerosis, amyotrophic lateral sclerosis, contact dermatitis, Ewing sarcoma, lymphoma, medulloblastoma, ependymoma, skin and prostate cancer). Multiple pathway analysis of clinical prostate cancer (PCa) studies showed increased AR activity in hyperplasia and primary PCa but variable AR activity in castrate resistant (CR) PCa, loss of TGFβ activity in PCa, increased Wnt activity in TMPRSS2:ERG fusion protein-positive PCa, active PI3K pathway in advanced PCa, and active PI3K and NFκB as potential hormonal resistance pathways. Potential value for future clinical practice includes disease subtyping and prediction and targeted therapy response prediction and monitoring.
In vitro culture with gemcitabine augments death receptor and NKG2D ligand expression on tumour cells
Authors: Gravett Andrew M. , Dalgleish Angus G. , Copier John
Published: February 2019

Much effort has been made to try to understand the relationship between chemotherapeutic treatment of cancer and the immune system. Whereas much of that focus has been on the direct effect of chemotherapy drugs on immune cells and the release of antigens and danger signals by malignant cells killed by chemotherapy, the effect of chemotherapy on cells surviving treatment has often been overlooked. In the present study, tumour cell lines: A549 (lung), HCT116 (colon) and MCF-7 (breast), were treated with various concentrations of the chemotherapeutic drugs cyclophosphamide, gemcitabine (GEM) and oxaliplatin (OXP) for 24 hours in vitro. In line with other reports, GEM and OXP upregulated expression of the death receptor CD95 (fas) on live cells even at sub-cytotoxic concentrations. Further investigation revealed that the increase in CD95 in response to GEM sensitised the cells to fas ligand treatment, was associated with increased phosphorylation of stress activated protein kinase/c-Jun N-terminal kinase and that other death receptors and activatory immune receptors were co-ordinately upregulated with CD95 in certain cell lines. The upregulation of death receptors and NKG2D ligands together on cells after chemotherapy suggest that although the cells have survived preliminary treatment with chemotherapy they may now be more susceptible to immune cell-mediated challenge. This re-enforces the idea that chemotherapy-immunotherapy combinations may be useful clinically and has implications for the make-up and scheduling of such treatments.
Functional random forest with applications in dose-response predictions
Authors: Rahman Raziur , Dhruba Saugato Rahman , Ghosh Souparno , Pal Ranadip
Published: February 2019

Drug sensitivity prediction for individual tumors is a significant challenge in personalized medicine. Current modeling approaches consider prediction of a single metric of the drug response curve such asAUCorIC50. However, the single summary metric of a dose-response curve fails to provide the entire drug sensitivity profile which can be used to design the optimal dose for a patient. In this article, we assess the problem of predicting the complete dose-response curve based on genetic characterizations. We propose an enhancement to the popular ensemble-based Random Forests approach that can directly predict the entire functional profile of a dose-response curve rather than a single summary metric. We design functional regression trees with node costs modified based on dose/response region dependence methodologies and response distribution based approaches. Our results relative to large pharmacological databases such as CCLE and GDSC show a higher accuracy in predicting dose-response curves of the proposed functional framework in contrast to univariate or multivariate Random Forest predicting sensitivities at different dose levels. Furthermore, we also considered the problem of predicting functional responses from functional predictorsi.e., estimating the dose-response curves with a model built on dose-dependent expression data. The superior performance of Functional Random Forest using functional data as compared to existing approaches have been shown using the HMS-LINCS dataset. In summary, Functional Random Forest presents an enhanced predictive modeling framework to predict the entire functional response profile considering both static and functional predictors instead of predicting the summary metrics of the response curves.