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First-in-class inhibitors of SbnA reduce siderophores production in Staphylococcus aureus
No full textSiderophores production, along with heme scavenging by hemophores, is one of the main mechanisms
exploited by bacteria to achieve iron supply. Staphylococcus aureus produces two main siderophores,
staphyloferrin A (SA) and staphyloferrin B (SB), with the latter produced only by the most invasive, coagulasepositive
S. aureus strains. Along the seven steps of SB biosynthetic pathway, SbnA catalyzes the crucial
formation of the intermediate N-2-amino-2-carboxyethyl-L-glutamate from L-O-phosphoserine and
glutamate. Our functional characterization of the enzyme highlighted that citrate inhibits SbnA with a Ki in
the order of magnitude of the physiological concentration of the metabolite. We searched for inhibitors of
SbnA within citrate analogues and identified 2-phenylmaleic acid (2-PhMA) as the best hit, with a Ki of 16 ± 2
μM and a mechanism of inhibition which is competitive with L-O-phosphoserine for active-site binding. The
methyl ester of 2-PhMA at 2 mM concentration resulted effective in inhibiting siderophore biosynthesis in S.
aureus. These results pave the way for the discovery of promising inhibitors of iron acquisition that might
find application as innovative antimicrobials
Abito e identità di genere. Il "femminile" tra ambiguità, androginia e unisex
No full textIl saggio esplora il ruolo dell'abbigliamento nella definizione dell'identità di genere. Gardellini analizza come la moda, considerata un'arte mutevole e quotidiana, sia un potente strumento culturale che riflette e influenza le convenzioni sociali e di genere. L'autrice discute l'adozione dell'abito maschile da parte delle donne come un atto di sfida alle norme sociali, esplorando concetti come il lesbismo e l'androginia. Gardellini esamina anche l'evoluzione storica dei pantaloni femminili, dal "bloomer" del XIX secolo ai tailleur con pantaloni e all'unisex degli anni Sessanta e Settanta. Conclude che l'abbigliamento è una modalità di rappresentazione e autorappresentazione che articola la psiche e il corpo, sottolineando l'ambivalenza e la complessità dell'identità di genere.
TUTTI A PRANZO DA TRIMALCIONE? L’IMMAGINARIO ALIMENTARE DI ROMA ANTICA DA PLAUTO A PETRONIO
No full textHistone H3 K4 trimethylation occurs mainly at the origins of polycistronic transcription in the genome of Leishmania infantum promastigotes and intracellular amastigotes
No full textBackground: Trypanosomatids include the genera Trypanosoma and Leishmania, which are the etiological agents of important human diseases. These pathogens present unique mechanisms of gene expression characterized by functionally unrelated genes positioned in tandem and organized into polycistronic transcription units transcribed in a large pre-mRNA by RNA Polymerase II. Since most of the genome is constitutively transcribed, gene expression is primarily controlled by post-transcriptional processes. As in other organisms, histones in trypanosomatids contain a considerable number of post-translational modifications, highly conserved across evolution, such as the acetylation and methylation of some lysines on histone H3 and H4. These modifications have been mainly studied in Trypanosoma spp. The aim of this work was to elucidate the distribution of histone H3 lysine 4 trimethylation (H3K4me3) over the chromatin landscape of Leishmania infantum, the causative agent of canine and human leishmaniasis in the Mediterranean region. To this end, we investigated by chromatin immunoprecipitation (ChIP)-sequencing either the promastigotes (the flagellated motile form) and the amastigotes (the intracellular form) in an in vitro infection model. Results: The chromatin was prepared from THP-1 cells non infected, THP-1 cells infected with L. infantum MHOM/FR/78/LEM75, and THP-1 cells non infected and mixed with L. infantum MHOM/FR/78/LEM75 promastigotes. ChIP was conducted using anti-H3K4me3 or anti-H3K27me3 antibodies and ChIP-seq was performed on an Ion S5 sequencer. We showed that histone H3K4me3 is mainly enriched at transcription start sites (67%) or internally within the polycistronic transcription units (30%), with no differences between L. infantum promastigotes and amastigotes. Moreover, the enriched regions co-localize with another hallmark of transcriptional activation (histone H3 acetylation) in L. major, a species characterized by a high degree of synteny with L. infantum. Conclusions: These findings expand our knowledge of the epigenomics of Leishmania parasites, focusing on epigenetic markers associated with transcription in L. infantum, and will contribute to elucidate the transcriptional mechanisms in these pathogens
Exploring the effects of decabromodiphenyl ether on meiofaunal communities: an experimental approach
No full textThis study investigates the ecotoxicological effects of BDE-209, a persistent organic pollutant (POP), prevalent in Kuwait's coastal-industrial zones, on meiofaunal communities. A mesocosm experiment was conducted, exposing sediment-dwelling meiofaunal communities from sediments near Failaka Island (Kuwait) to gradient concentrations of BDE-209 (0.01–20 mg/kg) over a 4-week period. The effect on meiofaunal communities was evaluated by changes in the taxonomic composition, alpha and beta diversity metrics, and the Nematodes/Copepods (Ne/Co) ratio. Our findings reveal that BDE-209 exposure significantly reduced alpha diversity and induced shifts in the community structure, favouring resilient taxa such as nematodes. The increasing Ne/Co ratio underscores structural changes and highlights the pollutant's potential to disrupt sedimentary ecosystem functions. Temporal analyses confirm the persistence of BDE-209 in sediments despite partial degradation, reinforcing its classification as a POP with long-term ecological risks. This study provides valuable insights into the responses of meiofaunal communities to POPs like BDE-209, demonstrating their efficacy as bioindicators for sediment quality. By integrating meiofaunal biomonitoring metrics with mesocosm experiments, this research provides a robust method for assessing the ecological impacts of BDE-209, particularly in regions lacking regulatory frameworks. It also raises awareness of the broader implications of POPs in marine ecosystems. These findings highlight the urgent need for enhanced monitoring programs and stricter regulations to mitigate PBDE contamination in marine ecosystems. Future research should focus on field-based validation of mesocosm results and investigate the interactive effects of BDE-209 with other pollutants to better understand its cumulative ecological impact
Are Transformers a Useful Tool for Tiny devices in Human Activity Recognition?
No full textHuman Activity Recognition using tiny wearable devices presents unique challenges due to limited computational resources and battery life. Transformers have recently emerged as the most effective tools for time-series classification. This is due to their capacity to capture long-range dependencies and complex temporal dynamics, combined with relatively lower computational complexity, which allows them to surpass the performance of more traditional systems such as convolutional or recurrent neural networks. In fact, transformers do not process data sequentially. Instead, they leverage an attention mechanism that allows them to weigh the importance of different parts of the input data differently. This study experimentally investigates the applicability of transformer models on tiny devices by porting them on a low-power ESP32 device. Comprehensive evaluations are conducted on several benchmark datasets, demonstrating that transformer-based models are not viable solutions for tiny devices compared to convolutional and recurrent neural networks, with respect to which it achieves up to 14% lower accuracy depending on the dataset used
Biodegradable lipid bilayer-assisted indocyanine green J- aggregates for photothermal therapy: Formulation, in vitro toxicity and in vivo clearance
No full textIndocyanine green (ICG) J-aggregates (IJA) are a unique form of aggregation that exhibits superior properties to monomeric ICG. Despite their higher photoacoustic (PA) signals for imaging and heating stability during photothermal therapy (PTT), they exhibit low stability under a biological milieu. Our group previously proposed a simple procedure for in-situ preparation of IJA into liposomes, accelerating their formation and optical properties. To comprehend their potential applications, we systematically investigated the effect of the lipid bilayer composition on ICG J-aggregation and stability. Moreover, their in vitro compatibility and photothermal toxicity in monolayers and cancer spheroids, besides their in vivo biodistribution and clearance were evaluated. Our findings revealed the importance of high cholesterol and PEG-lipid content and low charged lipids (∼ 5 mol %) in liposomes to promote a high IJA/ICG ratio and, thus, high heating stability. More importantly, IJA-liposomes revealed high biocompatibility in monolayer and cancer spheroids with efficient photothermal toxicity. Finally, IJA-liposomes were cleared from the body without toxicity. Interestingly, IJA-liposomes mainly showed lower affinity to the liver than monomeric ICG, resulting in higher renal clearance. Overall, our biodegradable IJA-liposomes could be an excellent alternative to gold-based agents suitable for PA imaging and cancer PTT
Fréchet and Gateaux gH-Differentiability for Interval Valued Functions of Multiple Variables
No full textIn this work we extend concepts of differentiability for Interval-Valued functions (IV-functions) of multiple variables, based on generalized Hukuhara gH-difference. In this context, we introduce a new concept of gH-linearity and characterize the class of gH-linear IV-functions, which are fundamental for a general approach to Fréchet-type and Gateaux-type gH-differentiability of the first order. We moreover consider vector IV-functions and outline the definition of the gH-Jacobian; by representing intervals and IV-functions in midpoint-radius notation, we establish properties and relations between pointwise, Fréchet and Gateaux gH-differentiability. Finally, higher-order differentiability and gH-Hessian matrix are considered. These intuitive concepts are mathematically and computationally easy to work with
Il potere normativo del Governo in Europa: un’analisi comparata a partire dai testi costituzionali
No full textThe essay offers a mapping of the themes and issues related to the exercise of the Government’s normative function in European countries where the legislative and executive branches are connected by a relationship of confidence. The examined European constitutions reflect the existence of a shared normative function between Parliament and Government. In particular, three distinct bases for conferring normative authority on the Government can be identified: a) the recognition of the power to adopt implementing reg-ulations of statutes and, at times, a general regulatory power; b) the delegation of normative authority to the Government by Parliament; c) the attribution of an autonomous normative power to the Government, linked either to a specific area of competence or to the occurrence of situations of urgency, necessity, or emergency.
In each legal system, the Government’s role in exercising the normative function results from the combina-tion of these different options and from the actual balance of power established between Parliament and Government. These considerations, together with data on the Government’s normative output, reveal the significant centrality of the executive in the production of legislation. This trend is consistent with the grow-ing prominence of Governments within the power dynamics of contemporary systems of government—fur-ther reinforced in recent years by the debt crisis and the Covid-19 pandemic. Within this framework, Italy holds a particularly distinctive position due to the Government’s prerogative to adopt two types of primary legislation—legislative decrees and law decrees—and the extensive use of both as a matter of practice