547 research outputs found
A novel Gcn5p inhibitor represses cell growth, gene transcription and histone acetylation in budding yeast
No full textHistone acetyltransferases are key chromatin regulators responsible for transcriptional activation and cell cycle progression. We propose a simple yeast-based assay to determine the specificity and targets of novel Gcn5p inhibitors. Here, we report the finding of a novel, small molecule, MC1626, which is able to inhibit yeast cell growth, Gcn5p-dependent gene transcription and acetylation of the histone H3 N-terminal tail in vivo. Because HATs misregulation is invariably associated with human diseases, the identification of MC1626 as a novel cell-permeable Gcn5p inhibitor suggests that it may be a very useful starting tool for the further development of new molecules to be applied to expression profiling of genes regulated by histone H3 acetylation. In addition, our results demonstrate that MC1626 is a Gcn5p-dependent yeast growth inhibitor
Independent Developers: The invisible urban regenerators
No full textMost of today’s urban development and regeneration is being provided by the private
sector. Cities are being regenerated and redeveloped by institutional developers with
projects that can change entire neighbourhoods and city centres. The majority of these
developers are interested primarily in institutional properties and other buildings that are
large enough to generate the required returns and revenues without bearing too much risks.
There are also areas and neighbourhoods that do not experience institutional development
and investment because their developmental values and sites are not encouraging to them.
Nevertheless, some of these areas gained economic growth and were regenerated without
any institutional developers being involved. These kinds of regenerations are either a result
of community development or they are the outcome of independent development. This type
of development culture is not much studied yet. Independent developers are the invisibles
working in the shadows of the big institutional property developers that are often covered in
the media and literature. Hardly anybody notices and writes about these small and
independent developers that, although developing smaller projects, still have an impact on
and are important for urban regeneration. This analysis of independent developers and their
projects will provide information on their approach to property development. The report will
discuss the major differences between institutional and independent development and how
they each address topics like location, market, intervention and funding. By drawing on
examples from interviews, literature and other publications, the report will examine
independent property developers in more detail and try to analyse their role and their
contribution to urban regeneration
Chemogenomic profiling of the cellular effects associated with histone H3 acetylation impairment by a quinoline-derived compound
No full textWe report the results of a chemogenomic profiling aimed to explore the mode of action of a quinolic analogue of the p300 histone acetyltransferase (HAT) inhibitor anacardic acid, named MC1626. This compound reduced histone H3 acetylation in a dose-dependent manner and the HATs Gcn5 and Rtt109, which specifically target H3 lysines, were the only ones that caused chemical-genetic synthetic sickness with MC1626 when mutated. Deletion of specific Gcn5 (e.g., Ada1) and Rtt109 (e.g., Asf1) multiprotein complex components also enhanced MC1626 sensitivity. In addition to N-terminal H3 lysines, MC1626 inhibits H3K56 acetylation, a histone modification that, in yeast, is exclusively supported by Rtt109 and indirectly influences DNA integrity. Several DNA repair mutants were found to be sensitive to MC1626. Functional links between histone acetylation impairment by MC1626 and mitochondrion as well as cytoskeleton functionality were also revealed, thus extending the range of non-nuclear processes that are influenced by histone acetylation. (C) 2010 Elsevier Inc. All rights reserved
Gcn5 histone acetyltransferase is present in the mitoplasts
No full textIn Saccharomyces cerevisiae the Lysine-acetyltransferase Gcn5 (KAT2) is part of the SAGA complex and is responsible for histone acetylation widely or at specific lysines. In this paper we report that GCN5 deletion differently affects the growth of two strains. The defective mitochondrial phenotype is related to a marked decrease in mtDNA content, which also involves the deletion of specific regions of the molecule. We also show that in wild-type mitochondria the Gcn5 protein is present in the mitoplasts, suggesting a new mitochondrial function independent from the SAGA complex and possibly a new function for this protein connecting epigenetics and metabolism
Integrative gene transfer in the truffleTuber borchii by Agrobacterium tumefaciens-mediated transformation
No full textAgrobacterium tumefaciens-mediated transformation is a powerful tool for reverse genetics and functional genomic analysis in a wide variety of plants and fungi. Tuber spp. are ecologically important and gastronomically prized fungi ("truffles") with a cryptic life cycle, a subterranean habitat and a symbiotic, but also facultative saprophytic lifestyle. The genome of a representative member of this group of fungi has recently been sequenced. However, because of their poor genetic tractability, including transformation, truffles have so far eluded in-depth functional genomic investigations. Here we report that A. tumefaciens can infect Tuber borchii mycelia, thereby conveying its transfer DNA with the production of stably integrated transformants. We constructed two new binary plasmids (pABr1 and pABr3) and tested them as improved transformation vectors using the green fluorescent protein as reporter gene and hygromycin phosphotransferase as selection marker. Transformants were stable for at least 12 months of in vitro culture propagation and, as revealed by TAIL- PCR analysis, integration sites appear to be heterogeneous, with a preference for repeat element-containing genome sites
SAGA complex and Gcn5 are necessary for respiration in budding yeast
No full textIn budding yeast, growth through fermentation and/or respiration is dependent on the type of carbon source
present in the medium. SAGA complex is themain acetylation complex and is required, togetherwith Rtg factors,
for nucleus-mitochondria communication and transcriptional activation of specific nuclear genes. Even though
acetylation is necessary formitochondria activity and respiratory pathways the direct role of histone acetyltransferases
and SAGA complex has never been investigated directly. In this study we demonstrate, for the first time,
that Gcn5 and SAGA are needed for respiratory metabolismand oxygen consumption. According to a central role
for acetylation in respirationwe find that the Gcn5 inhibitor CPTH2 had higher efficacy on cells grown in glycerol
containing media. We also demonstrated that the opposing activities of Gcn5 and Hda1 modify selectively H3-
AcK18 and are essential for respiration. Taken together our results suggest a novel paradigm coupling
acetyltransferase activity to respiratory metabolism. Correspondingly we propose the selective utilization of
KAT inhibitor CPTH2, combined to the modulation of the respiratory metabolism of the cell, as a promising
novel tool of intervention in cancer cell
The role of language typology on L2 acquisition and learning, Special Issue
No full textThis special issue of the I-LanD Journal aims to explore the role of
language typology on second language acquisition (SLA) and learning.
The contributions to this special issue address the question as to
whether and in which ways typological contrasts of languages play a
crucial role in how events are expressed in adult second language (L2).
In this regard, Slobin (1996), by means of his Thinking for Speaking
hypothesis, argues that differences across languages predispose native
speakers to view and to talk about events differently and this seems to
have important consequences in discourse conceptualisation and
production even at very advanced levels of L2 proficiency.
Research on typological variation across languages has been
conducted for decades and important advances have been made in the
domain. For instance, it is well known that Germanic vs Romance
native speakers differ in the ways they conceptualise and verbalise
events. Consequently, speakers diverge in the preferred perspective
selected with respect to conceptual domains such as aspect, time,
motion, modality, both at the sentence level (von Stutterheim 2003)
and at discourse level (Klein/von Stutterheim 2002; Carroll/Lambert
2006) and this is partly due to the typological properties of languages.
Most studies show the challenges adult L2 learners face in restructuring
these patterns in the process of acquisition of another language with a
different set of patterns. This hard task for learners implies full or
partial crosslinguistic influence (CLI, cf. McManus 2022 for a more
recent overview). The latter, often used interchangeably with transfer
(cf. Odlin 1989, 2003, 2005), refers to the search for similarities/
differences between one’s prior linguistic knowledge (from the L1 or
any other previously acquired languages) and learning, knowledge
and use of the new language (Jarvis/Pavlenko 2010: 1). CLI is a key
component of the L2 learning process, and it seems particularly
relevant when learners try to map L2 words into the concepts of their
L1. In this sense, SLA can be seen as cognitive restructuring (HijazoGascón 2021: 2), since learners can experience a cognitive dissonance
between the L2 lexical items and the L1 notions. The question of
whether L1 typological properties may be transferred or not in the L2
discourse has been largely explored for the cognitive domains of time
(e.g. von Stutterheim 2003 for ongoingness vs boundness; McManus/
Marsden 2017, Giuliano/Anastasio 2021a for time and aspect) and
Introduction: The Role
of Language Typology
on L2 Acquisition and Learning
Simona Anastasio
University of Toulouse Jean Jaurès, France
[email protected]
Patrizia Giuliano
University of Naples ‘Federico II’, Italy
[email protected]
DOI: 10.26379/IL2022002_000
4 I-LanD Journal. The role of language typology on L2 acquisiti on and learning · n. 2/2022 · eISSN 2532-764X
Simona Anastasio - Patrizia Giuliano
space (e.g. Cadierno/Ruiz 2006; Hendriks et al. 2008; Carroll et al.
2012; Hijazo-Gascón 2021) and, to a lesser extent, for syntax (e.g.
Giuliano/Anastasio 2021b). More recently, research has also focused
on the co-speech gestures in the expression of events. As such, the
literature shows that the ways L2 learners’ gestures can reveal how
they keep on gesturing as in their L1 rather than in the L2 native-like
manner (e.g. Gullberg 2009; Stam 2018, 2023).
In spite of the evident role of inter-typological contrasts during the
process of SLA (along with other important variables such as the L2
input exposure, the L2 proficiency level, individual factors) in terms of
CLI, there is little research that focuses on the impact of intratypological variation, i.e. typological differences or similarities
between languages of the same type (except for Ibarretxe-Antuñano
2009, 2015; Anastasio 2018, 2019, 2021, 2022). Additionally, the
impact of language typology is still far from being fully understood
and this is due to several reasons: a) native speakers’ preferences go
beyond the clear-cut typological classification when encoding the
intended message (Slobin 2006; von Stutterheim et al. 2009; Beavers
etal. 2010); b) most studies look at learners with an L1/L2 combination
belonging to different genetic and typological families and very few
consider the impact of the L1 when the learners’ languages in contact
are typologically close (except for Benazzo/Andorno 2017; Anastasio
2019, 2021, 2022; Saturno 2020; Hijazo-Gascón 2021) and can,
however, lack equivalent form-function categories.
This special issue brings together recent empirical research on
inter- and intratypological contrasts and their role on L2 acquisition
and learning. Specifically, drawing upon a functional perspective, this
special issue aims to add to the SLA field by offering recent empirical
studies relying on original data, involving: different types of tasks;
quantitative, qualitative and mixed-methods approaches; learners at
all stages of learning.
The key themes under focus explore morphological, syntactic, and
semantics differences between languages with their consequences for
framing events in L1 as well as in L2. In particular, three main domains
are investigated: a) affectedness; b) differential object marking; c)
space (static and dynamic location events). The data collected
represent a diversified selection of L1-L2 pairs: a) learners whose L1
and L2 are typologically and genetically closely-related (Isabel Repiso;
Jacopo Saturno); b) learners with an L1-L2 combination considered as
typologically distant (Christina Piot, Maria Hellerstedt); c) learners
whose L1 and L2 belong to different typological types but present
similarities in the linguistic devices for conveying events (Delia
Airoldi).
The first paper of this special issue deals with a still underexplored
domain in SLA functional approach, i.e. affectedness within Romance
languages. Specifically, Isabel Repiso examines the syntactic and
morphological realisation of affected arguments across two
typologically and genetically-related languages, French and Spanish,
and in L2 French of Spanish learners (A2-B2 levels of CEFR). The
crosslinguistic findings show different morpho-syntactic preferences
in French and Spanish productions to mark affectedness. As to L2
I-LanD Journal. The role of language typology on L2 acquisiti on and learning · n. 2/2022 · eISSN 2532-764X 5
Introduction: The Role of Language Typology on L2 Acquisition and Learning
results, CLI arises in terms of under/overuse of non-native like use of
L2 structures especially at less advanced stage. The author hypothesises
that, when confronting to the L2 verbalisation of a universal domain,
learners tend to rely on L2 constructions similar to those of the L1 as
a strategy to compensate lack of knowledge regarding TL uses.
Jacopo Saturno’s contribution also explores the morphosyntax
domain, by focusing on the differential object marking in nominal
morphology in L2 Polish of East Slavic learners (L1: Belorussian,
Russian, Ukrainian) of A1-B1 proficiency (CEFR). By means of a
quantitative study, the author confirms that CLI and universal
tendencies, such as markedness, may coexist as explanatory factors in
the differential object marking in an intercomprehension situation.
The subsequent three papers concern the role of typological
diversity in the expression of space in language. Christina Piot focuses
on multimodality in motion event construal. She first examines how
native speakers (French vs Dutch) express the same motion events in
their speech and co-speech gestures and then to what extent
multimodal and inter-/intralinguistic differences impact performances
of CLIL French learners of L2 Dutch (A1-B2 proficiency levels).
Participants were recruited in Belgium, whose context is not
particularly favourable for monolingual speakers, since it offers three
official languages: Flemish/Dutch speaking; Walloon/French speaking;
and, to a lesser extent, Ostbelgien German speaking. Analysis of
language use and gesture by native speakers shows not only
prototypical features of typological classifications, but also patterns
which are less typical of their language-category. As for L2 performance,
learners have their own thinking-for-speaking pattern which is inbetween the French and the Dutch tendencies. Moreover, the study
also highlights that gestures give information on event
conceptualisation.
With respect to a different language combination, Delia Airoldi’s
contribution also focuses on the expression of motion. Specifically, the
author compares the productions of native speakers of Italian and
German to the productions of German learners of L2 Italian
(intermediate and advanced) by using different types of stimuli. The
aim is to study inter- and intra-linguistic differences between German
and Italian and to see whether learners’ productions are target-like in
L2 motion event construal or still influenced by the L1 patterns.
In the final paper, Maria Hellerstedt discusses two types of space:
location and caused motion, as described by French and Swedish
native speakers and by intermediate and advanced French learners of
L2 Swedish. The larger goal is to investigate the semantic components
selected to describe static and dynamic location in L2 Swedish, namely
by means of posture verbs, and to identify learners’ strategies
(avoidance, over-using) justifying learners’ linguistic choices. On the
one hand, the paper shows the developmental trajectory of L2 Swedish
learners in the use of posture verbs in spatial events. On the other
hand, it highlights traces of CLI and other interlanguage strategies in
producing idiomatic posture verbs.
Taken together, the above contributions bring a timely update within
the research field of typology and L2 acquisition and learning by
6 I-LanD Journal. The role of language typology on L2 acquisiti on and learning · n. 2/2022 · eISSN 2532-764X
Simona Anastasio - Patrizia Giuliano
building on and complementing previous literature on the subject. In
particular, these papers provide empirical studies on different
linguistic domains, while offering new avenues for future research on
the issues under investigation in this special issue
Treatment of kidney clear cell carcinoma, lung adenocarcinoma and glioblastoma cell lines with hydrogels made of DNA nanostars
No full textOvercoming the systemic administration of chemotherapy to reduce drug toxicity and the application of personalised medicine are two of the major challenges in the treatment of cancer. To this aim, efforts are focused on finding novel nanomaterials for the targeted administration of drugs and bioactive molecules in the tumor sites. DNA-based hydrogels are promising candidates for these applications. However, while such materials are fairly known from a structural and physical standpoint, their effects on cell cultures are far less investigated. Here, we studied the biological response of three different cell lines (clear cell renal cell carcinoma 786-O, lung adenocarcinoma H1975 and glioblastoma U87MG) to the treatment with DNA-GEL - a DNA-based hydrogel composed of interacting DNA nanostars. Additionally, we investigated the structural modification of DNA-GELs under cell culture conditions. The results we collected show a cell type specificity of the response, with interesting implications for future applications
Role of yUbp8 in Mitochondria and Hypoxia Entangles the Finding of Human Ortholog Usp22 in the Glioblastoma Pseudo-Palisade Microlayer
No full textKAT Gcn5 and DUB Ubp8 are required for respiration and mitochondria functions in budding yeast, and in this study we show that loss of respiratory activity is acquired over time. Interestingly, we show that absence of Ubp8 allows cells to grow in hypoxic conditions with altered mitophagy. Comparatively, the aggressive glioblastoma (GBM) multiforme tumor shows survival mechanisms able to overcome hypoxia in the brain. Starting from yeast and our findings on the role of Ubp8 in hypoxia, we extended our analysis to the human ortholog and signature cancer gene Usp22 in glioblastoma tumor specimens. Here we demonstrate that Usp22 is localized and overexpressed in the pseudo-palisade tissue around the necrotic area of the tumor. In addition, Usp22 colocalizes with the mitophagy marker Parkin, indicating a link with mitochondria function in GBM. Collectively, this evidence suggests that altered expression of Usp22 might provide a way for tumor cells to survive in hypoxic conditions, allowing the escape of cells from the necrotic area toward vascularized tissues. Collectively, our experimental data suggest a model for a possible mechanism of uncontrolled proliferation and invasion in glioblastoma
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