Festina Lente: A Farewell from the Editor Merlo, Paola
Computational linguistics - Association for Computational Linguistics,
06/2018, Letnik:
44, Številka:
2
Journal Article
The integrative physiology of inter-organ communication in lipophagy regulation is not well understood. Lipophagy and the cytosolic lipases ATGL and HSL contribute to lipid droplet (LD) mobilization; ...however, whether autophagy proteins engage with lipases to promote lipid utilization remains unknown. Here, we show that cold induces autophagy in proopiomelanocortin (POMC) neurons and activates lipophagy in brown adipose tissue (BAT) and liver in mice. Targeted activation of autophagy in POMC neurons via intra-hypothalamic rapamycin is sufficient to trigger lipid utilization in room temperature-housed mice. Conversely, inhibiting autophagy in POMC neurons or in peripheral tissues or denervating BAT blocks lipid utilization. Unexpectedly, the autophagosome marker LC3 is mechanistically coupled to ATGL-mediated lipolysis. ATGL exhibits LC3-interacting region (LIR) motifs, and mutating a single LIR motif on ATGL displaces ATGL from LD and disrupts lipolysis. Thus, cold-induced activation of central autophagy activates lipophagy and cytosolic lipases in a complementary manner to mediate lipolysis in peripheral tissues.
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•Cold induces autophagy in the hypothalamus and lipophagy in brown fat and liver•Stimulating hypothalamic autophagy activates lipophagy at ambient temperature•Inhibiting CNS or peripheral autophagy or denervating BAT blocks lipid utilization•Lipophagy and cytosolic lipases display complementarity toward total lipolysis
Martinez-Lopez et al. show that cold exposure induces autophagy in POMC neurons, which is necessary to activate lipophagy in brown adipose tissue and liver through the sympathetic network. Direct crosstalk between autophagy proteins and lipases in peripheral lipid droplets ensure maximal lipolysis rates
To process language in a way that is compatible with human expectations in a communicative interaction, we need computational representations of lexical properties that form the basis of human ...knowledge of words. In this article, we concentrate on word-level semantics. We discuss key concepts and issues that underlie the scientific understanding of the human lexicon: its richly structured semantic representations, their ready and continual adaptability, and their grounding in crosslinguistically valid conceptualization. We assess the state of the art in natural language processing (NLP) in achieving these identified properties, and suggest ways in which the language sciences can inspire new approaches to their computational instantiation.
Clefts are understood as biclausal structures involving the movement of a clefted constituent from a lower clause, where it is generated, to a higher clause, where it is interpreted. Though both ...grammatical, subject and object clefts show signs of different acceptability in experimental settings. This degradation is ascribed to the fact that the object needs to cross an intervening subject, thus triggering intervention effects. In this paper, we show that intervention effects are also present in grammatical configurations, and give rise to lower-than-expected frequencies. Based on sets of features that play a role in the syntactic computation of locality, we compare the theoretically expected and the actually observed counts of features in a corpus of thirteen syntactically annotated treebanks for three languages (English, French, Italian). We find the quantitative effects predicted by the theory of intervention locality: object clefts are less frequent than expected in intervention configuration, while subject clefts are roughly as frequent as expected. We also find that the size of the effect is proportional to the number of features that give rise to the intervention effect. These results provide a three-fold contribution. First, they extend the empirical evidence in favour of the feature-based intervention theory of locality. Second, they provide theory-driven quantitative evidence, thus extending in a novel way the sources of evidence used to adjudicate theories. Finally, the paper provides a blueprint for future theory-driven quantitative investigations.
Significance The transcription factor p53 plays a critical role in the cellular response to DNA damage and has thus been studied intensively in oncogenesis research. However, the role that p53 plays ...in the response of postmitotic neurons to cellular stress has received less attention. Here we describe an unexpected neuroprotective role for p53 in an in vivo model of tau-mediated neurodegeneration relevant to Alzheimer's disease and related disorders. Further, we identify synaptic function as a novel target pathway for p53 in aging neurons, consistent with the growing evidence for synaptic pathology as an early event in neurodegenerative disease. Our study defines mechanistically a new, conserved role for p53 in protecting postmitotic neurons from degeneration during aging and disease.
DNA damage has been implicated in neurodegenerative disorders, including Alzheimer’s disease and other tauopathies, but the consequences of genotoxic stress to postmitotic neurons are poorly understood. Here we demonstrate that p53, a key mediator of the DNA damage response, plays a neuroprotective role in a Drosophila model of tauopathy. Further, through a whole-genome ChIP-chip analysis, we identify genes controlled by p53 in postmitotic neurons. We genetically validate a specific pathway, synaptic function, in p53-mediated neuroprotection. We then demonstrate that the control of synaptic genes by p53 is conserved in mammals. Collectively, our results implicate synaptic function as a central target in p53-dependent protection from neurodegeneration.
In the computational study of human intelligence, the language sciences are in the unique position of resting both on sophisticated theories and representations and on large amounts of observational ...data available for many languages. In this paper, we discuss some recent results, where large-scale, data-intensive computational modelling techniques are used to address fundamental linguistic questions on the quantitative properties of abstract grammatical representations. Specifically, we present a programme of research exemplified in three case studies to identify the causes of frequency differentials. In the area of word order, we discuss work that investigates whether typological and corpus frequencies are systematically correlated to abstract syntactic structures and to higher-level structural principles of minimisation and efficiency. In the area of verb meaning, corpus-based computational models are discussed that investigate how frequencies are correlated to well-known lexical effects in causative alternations and morphological marking. The large corpus-based, cross-linguistic component of the work and the abstract grammatical hypotheses on word order and verb meaning provide new empirical and computational evidence to the important debate on language variation, its extent and its limits and illustrate how to bring corpus-based computational methodology to bear on theoretical syntactic issues. In so doing, we help reduce the current gap between theoretical and computational linguistics.
The protein kinase mammalian Sterile 20-like kinase 1 (MST1) plays a critical role in the regulation of cell death. Recent studies suggest that MST1 mediates oxidative stress-induced neuronal cell ...death by phosphorylating the transcription factor FOXO3 at serine 207, a site that is conserved in other FOXO family members. Here, we show that MST1-induced phosphorylation of FOXO1 at serine 212, corresponding to serine 207 in FOXO3, disrupts the association of FOXO1 with 14-3-3 proteins. Accordingly, MST1 mediates the nuclear translocation of FOXO1 in primary rat cerebellar granule neurons that are deprived of neuronal activity. We also find a requirement for MST1 in cell death of granule neurons upon withdrawal of growth factors and neuronal activity, and MST1 induces cell death in a FOXO1-dependent manner. Finally, we show that the MST1-regulatory, scaffold protein Nore1 is required for survival factor deprivation induced neuronal death. Collectively, these findings define MST1-FOXO1 signaling as an important link survival factor deprivation-induced neuronal cell death with implications for our understanding of brain development and neurological diseases.
Abstract Human language relies on the correct processing of syntactic information, as it is essential for successful communication between speakers. As an abstract level of language, syntax has often ...been studied separately from the physical form of the speech signal, thus often masking the interactions that can promote better syntactic processing in the human brain. However, behavioral and neural evidence from adults suggests the idea that prosody and syntax interact, and studies in infants support the notion that prosody assists language learning. Here we analyze a MEG dataset to investigate how acoustic cues, specifically prosody, interact with syntactic representations in the brains of native English speakers. More specifically, to examine whether prosody enhances the cortical encoding of syntactic representations, we decode syntactic phrase boundaries directly from brain activity, and evaluate possible modulations of this decoding by the prosodic boundaries. Our findings demonstrate that the presence of prosodic boundaries improves the neural representation of phrase boundaries, indicating the facilitative role of prosodic cues in processing abstract linguistic features. This work has implications for interactive models of how the brain processes different linguistic features. Future research is needed to establish the neural underpinnings of prosody-syntax interactions in languages with different typological characteristics.
In this paper, we illustrate a novel method to translate a derivational explanation of Universal 20 into vectorial representations. We exploit this vectorial representation to answer a number of ...theoretical questions. First, we use linear regression to automatically rank the costs of different syntactic movements within this proposal and investigate some proposals on partial and complete movement. This investigation of movement suggests that the nature of the movement is important, while the importance of harmonic specification of functional categories, i.e. whether the movement is partial or complete, is more context-dependent. We then evaluate whether the base order dem num adj n is the best predictor of the typological facts. We compare different syntactic proposals on the position of numerals in the noun phrase. We find that a merge position of numerals higher than adjectives has better results in both methods. We also show, using this method, that the independently motivated low merge position for numerals can only be semantically motivated, which results in intra-linguistic variation, and is not a parametric choice.
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