bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of the spectraplakin gene Short stop induces a DNA damage response in Drosophila epithelia
Authors: Dewey Evan B. , Parra Amalia S. , Johnston Christopher A. 
Published: November 2020

AbstractEpithelia are an eminent tissue type and a common driver of tumorigenesis, requiring continual precision in cell division to maintain tissue structure and genome integrity. Mitotic defects often trigger apoptosis, impairing cell viability as a tradeoff for tumor suppression. Identifying conditions that lead to cell death and understanding the mechanisms behind this response are therefore of considerable importance. Here we investigated how epithelia of the Drosophila wing disc respond to loss of Short stop (Shot), a cytoskeletal crosslinking spectraplakin protein that we previously found to control mitotic spindle assembly and chromosome dynamics. In contrast to other known spindle-regulating genes, Shot knockdown induces apoptosis in the absence of Jun kinase (JNK) activation, but instead leads to elevated levels of active p38 kinase. Shot loss leads to double-strand break (DSB) DNA damage, and the apoptotic response is exacerbated by concomitant loss of p53. DSB accumulation is increased by suppression of the spindle assembly checkpoint, suggesting this effect results from chromosome damage during error-prone mitoses. Consistent with DSB induction, we found that the DNA damage and stress response genes, Growth arrest and DNA damage (GADD45) and Apoptosis signal-regulating kinase 1 (Ask1), are transcriptionally upregulated as part of the shot-induced apoptotic response. Finally, co-depletion of Shot and GADD45 induced significantly higher rates of chromosome segregation errors in cultured cells and suppressed shot-induced mitotic arrest. Our results demonstrate that epithelia are capable of mounting molecularly distinct responses to loss of different spindle-associated genes and underscore the importance of proper cytoskeletal organization in tissue homeostasis.
Inverse sex-based expression profiles of PTEN and Klotho in mice
Authors: de Mello Natalia Prudente , Andreotti Diana Zukas , Orellana Ana Maria , Scavone Cristoforo , Kawamoto Elisa Mitiko 
Published: November 2020

AbstractSex differences are considered predictive factors in the development of several neurological diseases, which are also known to coincide with impaired phosphoinositide 3-kinase (PI3K)-AKT pathway activity, an essential signaling cascade involved in the control of several cellular functions such as autophagy and apoptosis. Here, under physiological conditions, we show important sex differences in the underlying balancing mechanisms that lead to similar AKT activity levels and autophagy and apoptosis processes in the two sexes. We demonstrate inverse sex-based expression of PTEN and Klotho, two important proteins that are known to negatively regulate the AKT pathway, and inverse sex-dependent levels of mTOR and FoxO3a activity. Taken together, our findings indicate that inverse sex-based regulation may be one of the underlying balancing mechanisms that differ between the sexes and a possible cause of sex-based autophagic and apoptotic responses to triggering situations that can lead to a sex-based predisposition to some neurological diseases.
Combined light- and heat-induced shape memory behavior of anthracene-based epoxy elastomers
Authors: Li Yuzhan , Goswami Monojoy , Zhang Yuehong , Liu Tuan , Zhang Jinwen , Kessler Michael R. , Wang Liwei , Rios Orlando 
Published: November 2020

AbstractThe development of multi-stimuli-responsive shape memory polymers has received increasing attention because of its scientific and technological significance. In this work, epoxy elastomers with reversible crosslinks are synthesized by polymerizing an anthracene-functionalized epoxy monomer, a diepoxy comonomer, and a dicarboxylic acid curing agent. The synthesized elastomers exhibit active responses to both light and heat enabled by the incorporated anthracene groups. When exposed to 365 nm UV light, additional crosslinking points are created by the photo-induced dimerization of pendant anthracene groups. The formation of the crosslinking points increases modulus and glass transition temperature of the elastomers, allowing for the fixation of a temporary shape at room temperature. The temporary shape remains stable until an external heat stimulus is applied to trigger the scission of the dimerized anthracene, which reduces the modulus and glass transition temperature and allows the elastomers to recover their original shapes. The effects of external stimuli on the thermal and dynamic mechanical properties of the elastomers are investigated experimentally and are correlated with molecular dynamics simulations that reveal the changes of structure and dynamics of the anthracene molecules and flexible chains.
Serum trace metal association with response to erythropoiesis stimulating agents in incident and prevalent hemodialysis patients
Authors: Brier Michael E. , Gooding Jessica R. , Harrington James M. , Burgess Jason P. , McRitchie Susan L. , Zhang Xiaolan , Rovin Brad H. , Klein Jon B. , Himmelfarb Jonathan , Sumner Susan J. , Merchant Michael L. 
Published: November 2020

AbstractAlterations in hemodialysis patients’ serum trace metals have been documented. Early studies addressing associations levels of serum trace metals with erythropoietic responses and/or hematocrit generated mixed results. These studies were conducted prior to current approaches for erythropoiesis stimulating agent (ESA) drug dosing guidelines or without consideration of inflammation markers (e.g. hepcidin) important for regulation of iron availability. This study sought to determine if the serum trace metal concentrations of incident or chronic hemodialysis patients associated with the observed ESA response variability and with consideration to ESA dose response, hepcidin, and high sensitivity C-reactive protein levels. Inductively-coupled plasma-mass spectrometry was used to measure 14 serum trace metals in 29 incident and 79 prevalent dialysis patients recruited prospectively. We compared these data to three measures of ESA dose response, sex, and dialysis incidence versus dialysis prevalence. Hemoglobin was negatively associated with ESA dose and cadmium while positively associated with antimony, arsenic and lead. ESA dose was negatively associated with achieved hemoglobin and vanadium while positively associated with arsenic. ESA response was positively associated with arsenic. Vanadium, nickel, cadmium, and tin were increased in prevalent patients. Manganese was increased in incident patients. Vanadium, nickel, and arsenic increased with time on dialysis while manganese decreased. Changes in vanadium and manganese were largest and appeared to have some effect on anemia. Incident and prevalent patients’ chromium and antimony levels exceeded established accepted upper limits of normal.
Inhibitory effects of astaxanthin on postovulatory porcine oocyte aging in vitro
Authors: Jia Bao-Yu , Xiang De-Cai , Shao Qing-Yong , Zhang Bin , Liu Shao-Na , Hong Qiong-Hua , Quan Guo-Bo , Wu Guo-Quan 
Published: November 2020

AbstractMammalian oocytes represent impaired quality after undergoing a process of postovulatory aging, which can be alleviated through various effective ways such as reagent treatment. Accumulating evidences have revealed the beneficial effects of astaxanthin (Ax) as a potential antioxidant on reproductive biology. Here, porcine matured oocytes were used as a model to explore whether Ax supplement can protect against oocyte aging in vitro and the underlying mechanism, and therefore they were cultured with or without 2.5 μM Ax for an additional 24 h. Aged oocytes treated with Ax showed improved yield and quality of blastocysts as well as recovered expression of maternal genes. Importantly, oxidative stress in aged oocytes was relieved through Ax treatment, based on reduced reactive oxygen species and enhanced glutathione and antioxidant gene expression. Moreover, inhibition in apoptosis and autophagy of aged oocyte by Ax was confirmed through decreased caspase-3, cathepsin B and autophagic activities. Ax could also maintain spindle organization and actin expression, and rescue functional status of organelles including mitochondria, endoplasmic reticulum, Golgi apparatus and lysosomes according to restored fluorescence intensity. In conclusion, Ax might provide an alternative for ameliorating the oocyte quality following aging in vitro, through the mechanisms mediated by its antioxidant properties.
COL6A3 expression in adipose tissue cells is associated with levels of the homeobox transcription factor PRRX1
Authors: Dankel Simon N. , Grytten Elise , Bjune Jan-Inge , Nielsen Hans Jørgen , Dietrich Arne , Blüher Matthias , Sagen Jørn V. , Mellgren Gunnar 
Published: November 2020

AbstractFibrillar collagen COL6α3 in adipose tissue has been associated with obesity, inflammation, insulin resistance and cancer. We here aimed to identify novel transcriptional regulators of COL6A3 expression. Based on a transcriptome dataset of adipose tissue, we identified strong correlations for 56 genes with COL6A3 mRNA, including targets of TGF-β/SMAD signaling. Among the identified candidates, the homeobox transcription factor PRRX1 showed a particularly striking co-expression with COL6A3, validated across several different cohorts, including patients with extreme obesity, insulin sensitive and resistant obesity (subcutaneous and omental), after profound fat loss (subcutaneous), and lean controls (subcutaneous). In human and mouse adipose cells, PRRX1 knockdown reduced COL6A3 mRNA and PRRX1 overexpression transactivated a reporter construct with the endogenous human COL6A3 promoter. Stable PRRX1 overexpression in 3T3-L1 cells induced Col6a3 mRNA threefold specifically after adipogenic induction, whereas TGF-β1 treatment upregulated Col6a3 mRNA also in the preadipocyte state. Interestingly, pro-inflammatory stimulus (i.e., TNF-α treatment) decreased PRRX1-mediated Col6a3 transactivation and mRNA expression, supporting a role for this mechanism in the regulation of adipose tissue inflammation. In conclusion, we identified the homeobox factor PRRX1 as a novel transcriptional regulator associated with COL6A3 expression, providing new insight into the regulatory mechanisms of altered adipose tissue function in obesity and insulin resistance.
Super-enhancer in prostate cancer: transcriptional disorders and therapeutic targets
Authors: Chen Xuanrong , Ma Qianwang , Shang Zhiqun , Niu Yuanjie 
Published: November 2020

AbstractAbnormal activity of oncogenic and tumor-suppressor signaling pathways contributes to cancer and cancer risk in humans. Transcriptional dysregulation of these pathways is commonly associated with tumorigenesis and the development of cancer. Genetic and epigenetic alterations may mediate dysregulated transcriptional activity. One of the most important epigenetic alternations is the non-coding regulatory element, which includes both enhancers and super-enhancers (SEs). SEs, characterized as large clusters of enhancers with aberrant high levels of transcription factor binding, have been considered as key drivers of gene expression in controlling and maintaining cancer cell identity. In cancer cells, oncogenes acquire SEs and the cancer phenotype relies on these abnormal transcription programs driven by SEs, which leads to cancer cells often becoming addicted to the SEs-related transcription programs, including prostate cancer. Here, we summarize recent findings of SEs and SEs-related gene regulation in prostate cancer and review the potential pharmacological inhibitors in basic research and clinical trials.
Disrupting Plasmodium UIS3–host LC3 interaction with a small molecule causes parasite elimination from host cells
Authors: Setua Sonali , Enguita Francisco J. , Chora Ângelo Ferreira , Ranga-prasad Harish , Lahree Aparajita , Marques Sofia , Sundaramurthy Varadharajan , Mota Maria M. 
Published: November 2020

AbstractThe malaria parasite Plasmodium obligatorily infects and replicates inside hepatocytes surrounded by a parasitophorous vacuole membrane (PVM), which is decorated by the host-cell derived autophagy protein LC3. We have previously shown that the parasite-derived, PVM-resident protein UIS3 sequesters LC3 to avoid parasite elimination by autophagy from hepatocytes. Here we show that a small molecule capable of disrupting this interaction triggers parasite elimination in a host cell autophagy-dependent manner. Molecular docking analysis of more than 20 million compounds combined with a phenotypic screen identified one molecule, C4 (4-{[4-(4-{5-[3-(trifluoromethyl) phenyl]-1,2,4-oxadiazol-3-yl}benzyl)piperazino]carbonyl}benzonitrile), capable of impairing infection. Using biophysical assays, we established that this impairment is due to the ability of C4 to disrupt UIS3–LC3 interaction, thus inhibiting the parasite’s ability to evade the host autophagy response. C4 impacts infection in autophagy-sufficient cells without harming the normal autophagy pathway of the host cell. This study, by revealing the disruption of a critical host–parasite interaction without affecting the host’s normal function, uncovers an efficient anti-malarial strategy to prevent this deadly disease.
Stellar population astrophysics (SPA) with the TNG
Authors: Fanelli C. , Origlia L. , Oliva E. , Mucciarelli A. , Sanna N. , Dalessandro E. , Romano D. 
Published: November 2020

Context. High-resolution spectroscopy in the near-infrared (NIR) is a powerful tool for characterising the physical and chemical properties of cool-star atmospheres. The current generation of NIR echelle spectrographs enables the sampling of many spectral features over the full 0.9–2.4 μm range for a detailed chemical tagging.
Aims. Within the Stellar Population Astrophysics Large Program at the TNG, we used a high-resolution (R = 50 000) NIR spectrum of Arcturus acquired with the GIANO-B echelle spectrograph as a laboratory to define and calibrate an optimal line list and new diagnostic tools to derive accurate stellar parameters and chemical abundances.
Methods. We inspected several hundred NIR atomic and molecular lines to derive abundances of 26 different chemical species, including CNO, iron-group, alpha, Z-odd, and neutron-capture elements. We then performed a similar analysis in the optical using Arcturus VLT-UVES spectra.
Results. Through the combined NIR and optical analysis we defined a new thermometer and a new gravitometer for giant stars, based on the comparison of carbon (for the thermometer) and oxygen (for the gravitometer) abundances, as derived from atomic and molecular lines. We then derived self-consistent stellar parameters and chemical abundances of Arcturus over the full 4800–24 500 Å spectral range and compared them with previous studies in the literature. We finally discuss a number of problematic lines that may be affected by deviations from thermal equilibrium and/or chromospheric activity, as traced by the observed variability of He I at 10 830 Å.
Metonymic indeterminacy and metalepsis
Authors: Brdar-Szabó Rita , Brdar Mario 
Published: November 2020

Abstract
Given appropriate context, indeterminacy may
arise when a metonymic vehicle, i.e. the source, can be
simultaneously linked to more than one metonymic target. We claim
that this situation, akin to the phenomenon of metalepsis or
transgression in narratology, is not rare, but quite usual, and even
regular in certain contexts. This may lead to an increase of a
second-order type of anisomorphy, but ultimately leaves space for
dynamic meaning construal and optimizes texts coherence. In order to
accommodate metalepsis, we argue for an approach to metonymy not
based on mappings but on the activation of the source conceptual
cluster opening a mental space dynamically expanded or reduced so as
to fit the conceptual frame provided by the co(n)text of use.
The fabric of metaphor in discourse
Authors: Vereza Solange 
Published: November 2020

Abstract
The overall aim of this chapter is to contribute
to the debate around the controversy of what might be approached as
a conceptual or a local/situated metaphor, by elaborating on a
distinction between two theoretical levels. On the one hand, at the
level of the conceptual system, we have high-order,
off-line representations, such as conceptual
metaphors, and, on the other, at the level of use, there are
episodic, often deliberate, on-line
conceptualizations, such as situated metaphors.
Within a cognitive-discursive perspective, it is argued that these
two levels are articulated, in a coherent and systematic way, in
figurative language in use. An analysis of an extended situated
metaphor explored in an argumentative text illustrates the way this
articulation may be woven in discourse.
Mapping Eurolects
Authors: Mori Laura , Szmrecsanyi Benedikt 
Published: November 2020

Abstract
Based on the description of EU legislative varieties covering EU directives and their national laws of
implementation in 11 languages, we are interested in the extent to which Eurolects are similar to each other, above and beyond
trivial genealogical similarities. We thus utilise a variation-oriented aggregative analysis technique to address these questions:
(a) What is the precise extent to which Eurolects are similar to each other? (b) Are similarities predicted by extra-linguistic
affinities? (c) Do factors such as EU accession dates and language policy play a role in shaping the Eurolect clusters? Our
methodology starts out from a meticulously catalogued list of corpus-based and corpus-driven lexical and grammatical features. Through the observed
presence or absence of these features, we calculate in a second step the aggregate linguistic distances between all of the
Eurolects. Finally, in step three, we use a well-established technique, Multidimensional Scaling, to visualize and interpret the
Eurolect landscape.
Structural and functional variations of the perfect in the Lezgic
languages
Authors: Maisak Timur 
Published: November 2020

Abstract
The paper presents a study of the morphological
and semantic properties of the perfects in nine Lezgic languages,
the southern branch of the East Caucasian (Nakh-Daghestanian)
language family. Morphologically, the perfects belong to the
perfective subsystem. They are usually periphrastic, with a tendency
to become synthetic due to auxiliary loss or merger. The functions
of the perfects vary among the languages of the group, but mostly
include the ‘current relevance’ perfect proper and the resultative
(stative). The experiential meaning is associated with the perfect
only in a few languages. In two languages (Agul and Archi), the
perfect has further evolved into an indirective evidential past,
although the diachronically earlier perfect and resultative
functions are still retained. Throughout the paper, I compare the
perfects to the aorists, which are the most frequent perfective past
tenses of the Lezgic languages. The aorists are much less
polyfunctional than the perfects and are mostly synthetic, although
periphrastic source models are also attested for them.
Cross-linguistic parallels and contrasts in a contact language
perfect construction
Authors: Slomanson Peter 
Published: November 2020

Abstract
This paper is about semantically and
pragmatically comparable perfect constructions in the contact
languages Sri Lankan Malay (SLM) and Sri Lankan Portuguese (SLP).
The goal of the paper is to show that non-finite participles based
on a conjunctive participle model in the Sri Lankan linguistic area
convey perfect meaning and also combine with a semantically empty
auxiliary to form a periphrastic perfect construction in main
clauses. Irrespective of the similarities, the separability of the
auxiliary and the negation facts associated with the SLM
construction are suggestive of biclausal status, whereas the SLP
construction is simply agglutinative and monoclausal.
The diachrony of the perfect in Zapotec
Authors: Broadwell George Aaron 
Published: November 2020

Abstract
Colonial Valley Zapotec (CVZ) is the form of
Zapotec spoken in the Valley of Oaxaca during the Spanish colonial
period (ca 1550–1810 C.E.). CVZ is known to us from written
documents only. CVZ had a distinct perfect morpheme, which has
largely disappeared in modern Zapotec languages. This chapter
surveys descriptions of the perfect in colonial grammars, as well as
corpus evidence to describe the range of uses of perfect morphology.
It contrasts the colonial system with the aspectual system of modern
Zapotec to trace the diachronic development of aspectual morphology
in these languages.
More on hodiernality
Authors: Xiqués Teresa M. 
Published: November 2020

Abstract
This paper builds on previous work and aims to
examine one of the most striking differences between the uses of the
present perfect in languages such as Catalan and English, namely, a
hodiernal (‘today’) reading of the perfect available under certain
conditions in these Romance languages but not in English. I will
specifically look into (1) the competition between tenses, (2) the
role of temporal modification, and (3) the present tense. Taking
into account the semantics of the present tense and a split of the
perfect time interval and the reference time as in Pancheva & von Stechow
(2004), I will claim that the main difference that
distinguishes the hodiernal reading is due to a possible
specification of the event time on a fixed position on the time
line.
Language contact and competition in the periphrastic perfect in
Early English
Authors: Eitler Tamás , Vadász Gábor 
Published: November 2020

Abstract
Based on data drawn from the computerised
Helsinki Corpus, the paper investigates the
extent to which the use of competing English perfective auxiliaries
was influenced by language contact with Old Norse in the Late Old
English period. It is shown that as in the Danelaw areas the
have-perfect with mutative intransitive verbs was used
to a statistically significantly higher extent, Scandinavian
influence is probable. We argue that this influence is likely to
have been of inductive nature. In addition, it is revealed that the
Scandinavian trigger must have been working gradually, as predicted
by the S-curve model for linguistic change. The dispersion of the
have-perfect presented with exponential increases,
decreases and minor drops, suggesting no apparent catastrophic
reorganisation. A near-deterministic association between the number
of Scandinavian features within the Norsification Package and the
use of the have-perfect with mutative intransitives also
points to the important role of Scandinavian interference.
“Have-less perfects” in Norwegian
Authors: Eide Kristin Melum 
Published: November 2020

Abstract
The constructions I investigate in this paper
can all be subsumed under the heading ‘have-omission’. This is also
the traditional analysis, to assume an omission of a semantically
superfluous auxiliary in these structures. A different perspective
however, and one that I will advocate here, is that there was never
an auxiliary there in the first place. From this perspective, the
constructions thus do not lack a perfect auxiliary (as the term
‘have-omission’ dictates), but instead these constructions employ
what only morphologically looks like a supine, i.e. an uninflected
past participle, in a syntactic function where you would expect a
different form (i.e. a preterit or an infinitive). Semantically
these constructions display a modal reading; counterfactuality or
irrealis, which I argue is conveyed by the supine-looking from
itself, and a linguistic heritage from Old Norse. Their
morphological, semantic, and syntactic traits suggest a common
underlying explanation for these constructions, and instead of
attributing these features to an invisible auxiliary, my explanation
puts the emphasis on the contribution of the visible element, the
“supine”.