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Background: Carbapenemase-producing Klebsiella pneumoniae (CP-KP) represents a global threat to public health, with limited antimicrobial therapeutic options. In this study, we analyzed a ceftazidime/avibactam (CAZ-AVI)-resistant K. pneumoniae isolate obtained from a patient previously exposed to CAZ-AVI expressing a novel K. pneumoniae carbapenemase (KPC)-3 variant. Methods: Antimicrobial susceptibility testing was performed using reference broth microdilution. Whole-genome sequencing (WGS) was performed using Illumina and Nanopore Technologies. Short- and long-reads were combined with Unicycler. Assemblies were investigated for multilocus sequence typing (MLST), antimicrobial resistance genes, porins, and plasmids. Results: The K. pneumoniae isolate (KP_RM_1) was resistant to CAZ-AVI, expanded-spectrum cephalosporins, amikacin, ertapenem, and cefiderocol (FDC) but was susceptible to tigecycline, colistin, trimethoprim/sulfamethoxazole, meropenem–vaborbactam, and imipenem–relebactam. WGS revealed that the KP_RM_1 genome is composed of a single chromosome of 5 Mbp and five circular plasmids. Further analysis showed the presence of novel blaKPC-216 located on a 72 kb plasmid. KPC-216 differs from KPC-3 by a Lysin (K) insertion at position 168 (+K168). Conclusions: We report the identification of a new KPC-3 variant associated with CAZ-AVI resistance. The KPC variants associated with CAZ-AVI resistance should be determined to promptly inform clinicians and start the appropriate antimicrobial therapy.

Xylella fastidiosa subsp. pauca ST53 (Xfp) is a pathogenic bacterium causing one of the most severe plant diseases currently threatening the olive-growing areas of the Mediterranean, the Olive Quick Decline Syndrome (OQDS). The majority of the olive cultivars upon infections more or less rapidly develop severe desiccation phenomena, while few are resistant (e.g. Leccino and FS17), being less impacted by the infections. The present study contributes to elucidating the basis of the resistance phenomenon by investigating the influence of the composition of the xylem sap of plant species on the rate of bacterial multiplication. Xylem saps from Xfp host and non-host species were used for growing the bacterium in vitro, monitoring bacterial growth, biofilm formation, and the expression of specific genes. Moreover, species-specific metabolites, such as mannitol, quinic acid, tartaric acid, and choline were identified by non-targeted NMR-based metabolomic analysis in olive, grapevine, and citrus. In general, the xylem saps of immune species, including grapevine and citrus, were richer in amino acids, organic acids, and glucose. The results showed greater bacterial growth in the olive cultivar notoriously susceptible to Xfp (Cellina di Nardò), compared to that recorded in the resistant cultivar Leccino. Conversely, higher biofilm formation occurred in Leccino compared to Cellina di Nardò. Using the xylem saps of two Xfp-immune species (citrus and grapevine), a divergent bacterial behavior was recorded: low planktonic growth and biofilm production were detected in citrus compared to the grapevine. A parallel evaluation of the expression of 15 genes showed that Xfp directs its molecular functions mainly to virulence. Overall, the results gained through this multidisciplinary study contribute to extending the knowledge on the host-pathogen interaction, while confirming that the host response and resistance mechanism have a multifactorial basis, most likely with a cumulative effect on the phenotype.

All cells require sustained intracellular energy flux, which is driven by redox chemistry at the subcellular level. NAD+, its phosphorylated variant NAD(P)+, and its reduced forms NAD(P)/NAD(P)H are all redox cofactors with key roles in energy metabolism and are substrates for several NAD-consuming enzymes (e.g. poly(ADP-ribose) polymerases, sirtuins, and others). The nicotinamide salvage pathway, constituted by nicotinamide mononucleotide adenylyltransferase (NMNAT) and nicotinamide phosphoribosyltransferase (NAMPT), mainly replenishes NAD+ in eukaryotes. However, unlike NMNAT1, NAMPT is not known to be a nuclear protein, prompting the question of how the nuclear NAD+ pool is maintained and how it is replenished upon NAD+ consumption. In the present work, using human and murine cells; immunoprecipitation, pulldown, and surface plasmon resonance assays; and immunofluorescence, small-angle X-ray scattering, and MS-based analyses, we report that GAPDH and NAMPT form a stable complex that is essential for nuclear translocation of NAMPT. This translocation furnishes NMN to replenish NAD+ to compensate for the activation of NAD-consuming enzymes by stressful stimuli induced by exposure to H2O2 or S-nitrosoglutathione and DNA damage inducers. These results indicate that by forming a complex with GAPDH, NAMPT can translocate to the nucleus and thereby sustain the stress-induced NMN/NAD+ salvage pathway.

Epistemological contestation about what – and whose – knowledge counts is central to the struggle about the future of wild horses on US public lands. In the politics of wild horse management, the construction of knowledge claims about wild horses as well as the formation of beliefs about their credibility is shaped by interspecies affective relations; relations that, we contend, are strikingly gendered. We seek to understand how these affective relations – the intermingling of facts and values – shape knowledge claims concerning wild horse roundups and removals carried out on federal lands managed by the Bureau of Land Management (BLM). Using data collected from 28 roundups and removals conducted between 2020 and 2022, in 7 states, we show that BLM’s disavowal of emotion in wild horse management places both wild horses and wild horse advocates in the same subaltern category of being destructive, disruptive, and out of place – in short, “feral.” The wild horse advocacy practices of witnessing roundups and removals of free-roaming horses from a position of “entangled empathy” discussed in this article reject this double-feralization of wild horses and the humans who care for them by establishing that wild horses are grievable, have ecological value, and are capable of participating in relations of interspecies kinship. We elaborate on these claims in terms of four major themes found in our data: protecting ecological integrity, regulating horses’ numbers, listening to nonhuman others, and debating advocacy strategies. Improved understanding of the political function of emotion helps identify a path toward managing wild horses more compassionately.

The investigation of intertextuality within a corpus of Latin poetry is the main objective of the research functions of the so-called ‘Musisque Deoque Galaxy’: formular recurrences, and lexical and metric-verbal co-occurrences draw a dense network of relationships between texts, where poetic memory presents itself in various modalities. This contribution aims to analyse the latest developments in the “Musisque Deoque Galaxy” both from the point of view of the tools created to enable new textual acquisitions and new analyses, and from the technological point of view, with reference to the work carried out to ensure a long-term sustainability.

The notes Giorgio Bassani wrote on his books represent a privileged access to his workshop, allowing us to reconstruct the genesis of the works and the intellectual profile of an important 20th century writer. When it comes to publishing, however, they pose numerous problems of classification, representation and systematisation of the data, against which the digital tool proves to be extremely advantageous. This contribution reflects on this theme, presenting the prototype of a digital edition built on the case study of Bassani's annotations to La scuola dell’uomo by Guido Calogero (Firenze, Sansoni, 1939) and reasoning on the important potential of XML-TEI markup in the treatment and representation of a complex, structured and sometimes elusive textual object such as the note.

Abstract Deregulation of protein synthesis and ER stress/unfolded protein response (ER stress/UPR) have been reported in astrocytes. However, the relationships between protein synthesis deregulation and ER stress/UPR, as well as their role in the altered homeostatic support of Alzheimer’s disease (AD) astrocytes remain poorly understood. Previously, we reported that in astrocytic cell lines from 3xTg-AD mice (3Tg-iAstro) protein synthesis was impaired and ER-mitochondria distance was reduced. Here we show that impaired protein synthesis in 3Tg-iAstro is associated with an increase of p-eIF2α and downregulation of GADD34. Although mRNA levels of ER stress/UPR markers were increased two-three-fold, we found neither activation of PERK nor downstream induction of ATF4 protein. Strikingly, the overexpression of a synthetic ER-mitochondrial linker (EML) resulted in a reduced protein synthesis and augmented p-eIF2α without any effect on ER stress/UPR marker genes. In vivo, in hippocampi of 3xTg-AD mice, reduced protein synthesis, increased p-eIF2α and downregulated GADD34 protein were found, while no increase of p-PERK or ATF4 proteins was observed, suggesting that in AD astrocytes, both in vitro and in vivo, phosphorylation of eIF2α and impairment of protein synthesis are PERK-independent. Next, we investigated the ability of 3xTg-AD astrocytes to support metabolism and function of other cells of the central nervous system. Astrocyte-conditioned medium (ACM) from 3Tg-iAstro cells significantly reduced protein synthesis rate in primary hippocampal neurons. When added as a part of pericyte/endothelial cell (EC)/astrocyte 3D co-culture, 3Tg-iAstro, but not WT-iAstro, severely impaired formation and ramification of tubules, the effect, replicated by EML overexpression in WT-iAstro cells. Finally, a chemical chaperone 4-phenylbutyric acid (4-PBA) rescued protein synthesis, p-eIF2α levels in 3Tg-iAstro cells and tubulogenesis in pericyte/EC/3Tg-iAstro co-culture. Collectively, our results suggest that a PERK-independent, p-eIF2α-associated impairment of protein synthesis compromises astrocytic homeostatic functions, and this may be caused by the altered ER-mitochondria interaction.

In this article we introduce a formal approach to the evolution of documents with particular attention to the philological perspective and the typical related issues. We propose a mathematical model capable of formalizing various complex phenomena in various research fields such as Computational Linguistics, Digital Philology and Software Engineering, in particular when this is applied to the analysis of documents and texts of historical and literary interest.

Curcumin-based fluorescent probes are presented that are able to selectively bind to aldehyde dehydrogenase 1A3 (ALDH1A3), an enzyme overexpressed in glioma stem cells and specifically identify glioblastoma cells in vitro and in vivo.

Due to its simple and beautiful architectural appearance, the stress‐ribbon bridge (SRB) has been gradually built around the world as a pedestrian or traffic bridge. However, as characterized by low bending stiffness and low damping ratio features, SRB is prone to the dynamic effects of external excitations, such as pedestrians, vehicles, and/or winds. To control the vertical vibration of the SRB, a rail‐damper system is proposed in this study. In the proposed scheme, the rotation of the handrails triggered by the flexural deformation of the SRB is utilized to drive the viscous dampers installed between the adjacent handrails. The governing equations of the proposed control system are established. The key design parameters and their influences on the dynamic properties of the control system are systematically investigated. The control performances of the proposed rail‐damper system are further investigated through an SRB numerical model subjected to pedestrian excitations. It is discovered that the rail‐damper system can offer considerable supplemental damping to the structural modes through reasonable design, achieving satisfactory control performances. To gain the excellent effect of the proposed rail‐damper system in real applications, a nondimensional rail stiffness of no less than 1000 is recommended, and the stiffness of the damper should be controlled as small as possible. [ABSTRACT FROM AUTHOR]

In the presence of spacetime torsion, the momentum components do not commute; therefore, in quantum field theory, summation over the momentum eigenvalues will replace integration over the momentum. In the Einstein–Cartan theory of gravity, in which torsion is coupled to spin, the separation between the eigenvalues increases with the magnitude of the momentum. Consequently, this replacement regularizes divergent integrals in Feynman diagrams with loops by turning them into convergent sums. In this article, we apply torsional regularization to the self-energy of a charged lepton in quantum electrodynamics. We show that torsion eliminates the ultraviolet divergence of the standard self-energy. We also show that the infrared divergence is absent. In the end, we calculate the finite bare masses of the electron, muon, and tau lepton: 0.4329 MeV , 90.95 MeV , and 1543 MeV , respectively. These values constitute about 85% of the observed, re-normalized masses. [ABSTRACT FROM AUTHOR]

Although corn is the most important and nitrogen (N)-fertilized crop, there is a lack of long-term data on the effects of organic and inorganic N fertilizers on the N balance and losses for corn systems under different tillage approaches. From 2012 to 2023, we assessed the effects of the N source on the grain yields from cultivated continuous corn receiving irrigation at a site with minimal erosion in Fort Collins, Colorado, USA, and compared these effects to no-till (NT) and strip till (ST) systems receiving inorganic N. An N balance accounting for N and carbon (C) sequestration found a system nitrogen use efficiency (NUESys) for organic N fertilizer (manure) with a tillage of 86.6%, which was higher than the NUESys of 62.6% with inorganic N fertilizer (enhanced efficiency fertilizer, EEF). Conventional tillage with manure use is a good management practice that contributed to higher grain yields (2 of 11 years), C sequestration (p < 0.05), soil organic N content (p < 0.05), and soil phosphorus (P) content than inorganic N fertilizer with tillage (p < 0.05). The tilled systems, whether receiving organic or inorganic N fertilizer, had higher yields and grain N content than the NT and ST systems receiving inorganic N fertilizer (p < 0.05). The grain production of the cultivated system receiving organic N fertilizer did not decrease with time, while the yields of the cultivated system receiving inorganic N fertilizer decreased with time (p < 0.05), suggesting that cultivated systems receiving organic N fertilizer may be more sustainable and better able to adapt to a changing climate. Additionally, a combination of manure (30% of N input) with EEF (70% of N input) contributed to a synergistic effect that increased the agronomic productivity (harvested grain yields). [ABSTRACT FROM AUTHOR]

The emergence of new plant diseases is an increasingly important concern. Climate change is likely to be among the factors causing most of the emerging diseases endangering forest and tree heritage around the world. Such diseases may be caused by latent pathogens or microorganisms cryptically associated with plants. The shift from a non-pathogenic to a pathogenic stage may depend on physiological alterations of the host, environmental changes, and/or stress factors. In some woods of the Salento Peninsula (Apulia Region, Italy), sudden declines of holm oak plants (Quercus ilex L.) have been observed since 2016. The morphological and molecular characterization of representative fungal isolates associated with cankers and necrosis in declining plants indicated that these isolates belong to the Botryosphaeriaceae family, and the most frequent species were Diplodia corticola and Diplodia quercivora, followed by Neofusicoccum vitifusiforme. In artificially inoculated young holm oak plants, both D. corticola and D. quercivora species produced intense and severe subcortical and leaf margin necrosis. N. vitifusiforme, although less aggressive, induced the same symptoms. Our research, in addition to confirming the involvement of D. corticola in olm oak decline, represents the first report of D. quercivora as a new pathogen of Q. ilex in Italy. Furthermore, to the best of our knowledge, we also found N. vitifusiforme as a new pathogen of Q. ilex.

Introduction to the AIUCD2021 conference proceedings.

Abstract Krabbe disease (KD; or globoid cell leukodystrophy) is an autosomal recessive lysosomal storage disorder caused by deficiency of the galactosylceramidase (GALC) enzyme. No cure is currently available for KD. Clinical applied treatments are supportive only. Recently, we demonstrated that two differently acting autophagy inducers (lithium and rapamycin) can improve some KD hallmarks in‐vitro, laying the foundation for their in‐vivo pre‐clinical testing. Here, we test lithium carbonate in‐vivo, in the spontaneous mouse model for KD, the Twitcher (TWI) mouse. The drug is administered ad libitum via drinking water (600 mg/L) starting from post natal day 20. We longitudinally monitor the mouse motor performance through the grip strength, the hanging wire and the rotarod tests, and a set of biochemical parameters related to the KD pathogenesis [i.e., GALC enzymatic activity, psychosine (PSY) accumulation and astrogliosis]. Additionally, we investigate the expression of some crucial markers related to the two pathways that could be altered by lithium: the autophagy and the β‐catenin‐dependent pathways. Results demonstrate that lithium has not a significant rescue effect on the TWI phenotype, although it can slightly and transiently improves muscle strength. We also show that lithium, with this administration protocol, is unable to stimulate autophagy in the TWI mice central nervous system, whereas results suggest that it can restore the β‐catenin activation status in the TWI sciatic nerve. Overall, these data provide intriguing inputs for further evaluations of lithium treatment in TWI mice.