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This article aims at clarifying Antonio Gramsci’s influence on Antonio La Penna, one of the most important Italian Classicists. It will show how Antonio Gramsci’s works provided La Penna with several categories which were fundamental in his analysis of both Latin literature and Roman society. Moreover, I will argue that Gramsci’s thought represented for La Penna a doorway to Marxism in the postwar period, and subsequently a way to overcome it. In fact, the reading of Gramsci’s work determined La Penna’s constant attempt to emancipate himself from Idealism. As matter of facts, this philosophy deeply characterised the training he received during his childhood and youth in the Italian school system which was dominated by the figure of Giovanni Gentile throughout the thirties and the early fourties.

Reward cues are often ambiguous; what is good in one context is not necessarily good in another context. To solve this ambiguity, animals form hierarchical associations in which the context acts as a gatekeeper in the retrieval of the appropriate cue-evoked memory, ensuring context-appropriate behavior. These hierarchical associative structures also influence future learning by promoting the formation of new context-dependent associations (leading to the inference of context-dependency for new associations). The orbitofrontal cortex (OFC) and the dorsal hippocampus (DH) are both proposed to encode a “cognitive map” that includes the representation of hierarchical, context-dependent, associations. However the causal role of the OFC and DH in the different functional properties of hierarchical associations remains controversial. Here we used chemogenetic inactivations, in rats, to examine the role of OFC and DH in 1) the contextual regulation of performance, and 2) the contextual learning bias conferred by hierarchical associations. We show that OFC is required for both manifestations of hierarchical associations. In contrast, DH contribution appears limited to the contextual learning bias. This study provides novel insight into the different functional properties of context-dependent hierarchical associations, and establishes the OFC as a critical orchestrator of these different contextual effects.

Meningiomas, although mostly benign, can be recurrent and fatal. World Health Organization (WHO) grading of the tumor does not always identify high-risk meningioma, and better characterizations of their aggressive biology are needed. To approach this problem, we combined 13 bulk RNA sequencing (RNA-seq) datasets to create a dimension-reduced reference landscape of 1,298 meningiomas. The clinical and genomic metadata effectively correlated with landscape regions, which led to the identification of meningioma subtypes with specific biological signatures. The time to recurrence also correlated with the map location. Further, we developed an algorithm that maps new patients onto this landscape, where the nearest neighbors predict outcome. This study highlights the utility of combining bulk transcriptomic datasets to visualize the complexity of tumor populations. Further, we provide an interactive tool for understanding the disease and predicting patient outcomes. This resource is accessible via the online tool Oncoscape, where the scientific community can explore the meningioma landscape.

Central nervous system (CNS) embryonal tumors are a heterogeneous group of high-grade malignancies, and the increasing clinical use of methylation profiling and next-generation sequencing has led to the identification of molecularly distinct subtypes. One proposed tumor type, CNS tumor with BRD4::LEUTX fusion, has been described. As only a few CNS tumors with BRD4::LEUTX fusions have been described, we herein characterize a cohort of 9 such cases (4 new, 5 previously published) to further describe their clinicopathologic and molecular features. We demonstrate that CNS embryonal tumor with BRD4::LEUTX fusion comprises a well-defined methylation class/cluster. We find that patients are young (4 years or younger), with large tumors at variable locations, and frequently with evidence of leptomeningeal/cerebrospinal fluid (CSF) dissemination. Histologically, tumors were highly cellular with high-grade embryonal features. Immunohistochemically, 5/5 cases showed synaptophysin and 4/5 showed OLIG2 expression, thus overlapping with CNS neuroblastoma, FOXR2-activated. DNA copy number profiles were generally flat; however, two tumors had chromosome 1q gains. No recurring genomic changes, besides the presence of the fusion, were found. The LEUTX portion of the fusion transcript was constant in all cases assessed, while the BRD4 portion varied but included a domain with proto-oncogenic activity in all cases. Two patients with clinical follow up available had tumors with excellent response to chemotherapy. Two of our patients were alive without evidence of recurrence or progression after gross total resection and chemotherapy at 16 and 33 months. One patient relapsed, and the last of our four patients died of disease one month after diagnosis. Overall, this case series provides additional evidence for this as a distinct tumor type defined by the presence of a specific fusion as well as a distinct DNA methylation signature. Studies on larger series are required to further characterize these tumors.

Aim: Marine biodiversity faces unprecedented threats from anthropogenic climate change. Ecosystem responses to climate change have exhibited substantial variability in the direction and magnitude of redistribution, posing challenges for developing effective climate-adaptive marine management strategies. Location: The California Current Ecosystem (CCE), USA. Methods: We project suitable habitat for 10 highly migratory species in the California Current System using an ensemble of three high-resolution (~10 km) downscaled ocean projections under the Representative Concentration Pathway 8.5 (RCP8.5). Spanning the period from 1980 to 2100, our analysis focuses on assessing the direction and distance of distributional shifts, as well as changes in core habitat area for each species. Results: Our findings reveal a divergent response among species to climate impacts. Specifically, four species were projected to undergo significant poleward shifts exceeding 100 km, and gain habitat (~7%–60%) in response to climate change. Conversely, six species were projected to shift towards the coast, resulting in a loss of habitat ranging from 10% to 66% by the end of the century. These divergent responses could typically be characterized by the mode of thermoregulation (i.e. ectotherm vs. endotherm) and species' affiliations with cool and productive upwelled waters that are characteristic of the region. Furthermore, our study highlights an increase in niche overlap between protected species and those targeted by fisheries, which may lead to increased human interaction events under climate change. Main Conclusions: By providing valuable species distribution projections, our research contributes to the understanding of climate change effects on marine biodiversity and offers critical insight and support for developing climate-ready management of protected and fished species.

BackgroundFrontotemporal lobar degeneration (FTLD) is a leading cause of dementia in individuals aged

The management and conservation of tuna and other transboundary marine species have to date been limited by an incomplete understanding of the oceanographic, ecological and socioeconomic factors mediating fishery overlap and interactions, and how these factors vary across expansive, open ocean habitats. Despite advances in fisheries monitoring and biologging technology, few attempts have been made to conduct integrated ecological analyses at basin scales relevant to pelagic fisheries and the highly migratory species they target. Here, we use vessel tracking data, archival tags, observer records, and machine learning to examine inter- and intra-annual variability in fisheries overlap (2013–2020) of five pelagic longline fishing fleets with North Pacific albacore tuna (Thunnus alalunga, Scombridae). Although progressive declines in catch and biomass have been observed over the past several decades, the North Pacific albacore is one of the only Pacific tuna stocks primarily targeted by pelagic longlines not currently listed as overfished or experiencing overfishing. We find that fishery overlap varies significantly across time and space as mediated by (1) differences in habitat preferences between juvenile and adult albacore; (2) variation of oceanographic features known to aggregate pelagic biomass; and (3) the different spatial niches targeted by shallow-set and deep-set longline fishing gear. These findings may have significant implications for stock assessment in this and other transboundary fishery systems, particularly the reliance on fishery-dependent data to index abundance. Indeed, we argue that additional consideration of how overlap, catchability, and size selectivity parameters vary over time and space may be required to ensure the development of robust, equitable, and climate-resilient harvest control rules.

Abstract Background Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by increased levels of inflammation that primarily manifests in the joints. Macrophages act as key drivers for the progression of RA, contributing to the perpetuation of chronic inflammation and dysregulation of pro-inflammatory cytokines such as interleukin 1 (IL-1). The goal of this study was to develop a macrophage-based cell therapy for biologic drug delivery in an autoregulated manner. Methods For proof-of-concept, we developed “smart” macrophages to mitigate the effects of IL-1 by delivering its inhibitor, IL-1 receptor antagonist (IL-1Ra). Bone marrow-derived macrophages were lentivirally transduced with a synthetic gene circuit that uses an NF-κB inducible promoter upstream of either the Il1rn or firefly luciferase transgenes. Two types of joint like cells were utilized to examine therapeutic protection in vitro, miPSCs derived cartilage and isolated primary mouse synovial fibroblasts while the K/BxN mouse model of RA was utilized to examine in vivo therapeutic protection. Results These engineered macrophages were able to repeatably produce therapeutic levels of IL-1Ra that could successfully mitigate inflammatory activation in co-culture with both tissue-engineered cartilage constructs and synovial fibroblasts. Following injection in vivo, macrophages homed to sites of inflammation and mitigated disease severity in the K/BxN mouse model of RA. Conclusion These findings demonstrate the successful development of engineered macrophages that possess the ability for controlled, autoregulated production of IL-1 based on inflammatory signaling such as via the NF-κB pathway to mitigate the effects of this cytokine for applications in RA or other inflammatory diseases. This system provides proof of concept for applications in other immune cell types as self-regulating delivery systems for therapeutic applications in a range of diseases.

Abstract Background Soil-transmitted helminths infect an estimated 18% of the world’s population, causing a significant health burden. Microscopy has been the primary tool for diagnosing eggs from fecal samples, but its sensitivity drops in low-prevalence settings. Quantitative real-time polymerase chain reaction (qPCR) is slowly increasing in research and clinical settings. However, there is still no consensus on preferred qPCR targets. Methods We aimed to compare soil-transmitted helminth (STH) DNA detection methods by testing naïve stool samples spiked with known quantities of STH eggs and larvae. DNA extracts from spiked samples were tested using independent quantitative realtime PCR (qPCR) assays targeting ribosomal or putative non-protein coding satellite sequences. Results For Trichuris trichiura, there was a strong correlation between egg/larvae counts and qPCR results using either qPCR method (0.86 and 0.87, respectively). Strong correlations also existed for A. lumbricoides (0.60 and 0.63, respectively), but weaker correlations were found for Ancylostoma duodenale (0.41 for both assays) and Strongyloides stercoralis (0.48 and 0.65, respectively). No correlation for Necator americanus was observed when testing with either qPCR assay. Both assays had fair-to-moderate agreement across targets when using field-collected stool samples (0.28–0.45, for all STHs), except for S. stercoralis (0.12) with slight agreement. Conclusions There is a strong correlation between qPCR results and egg/larvae counts. Our study confirms that qPCR is an effective diagnostic tool, even with low-intensity infections, regardless of the DNA-based diagnostic marker used. However, the moderate agreement between the two different qPCR assays when testing field samples highlights the need to understand the role of these targets in the genome so that the parasite burden can be quantified more accurately and consistently by qPCR. Graphical abstract

Calcifications on mammography from systemic disease at times meet diagnostic criteria for histologic sampling to exclude malignancy. We present a case of bilateral groups of new calcifications on mammography that yielded amyloidosis on core biopsy. Awareness of our patient's known diagnosis of systemic light chain amyloidosis (AL) prompted use of Congo red staining to confirm the histologic diagnosis. Knowledge of systemic diseases with possible manifestations on mammography can facilitate cogent and clinically relevant radiology-pathology correlation.

Student hazing activities on American college campuses have resulted in numerous deaths reported in the news media. Despite regular reports on hazing-related fatalities, no research has examined how these deaths are reported. The current study aims to bridge this research gap by analyzing articles covering hazing deaths in the U.S. between 1994 and 2019. The analysis reveals consistent patterns highlighting the influence of alcohol, different classifications of deaths, punitive responses, and the emotional reactions of the campus community. While these reports provide records of important and tragic events, their recurrent publication may bias understandings of the relative risk of student hazing, particularly fraternity hazing. Based on these findings, we make several recommendations for reporting on hazing deaths and future research directions.

Some evidence suggests a biphasic pattern of changes in cortical thickness wherein higher, rather than lower, thickness is associated with very early Alzheimer's disease (AD) pathology. We examined whether integrating information from AD brain signatures based on mean diffusivity (MD) can aid in the interpretation of cortical thickness/volume as a risk factor for future AD-related changes. Participants were 572 men in the Vietnam Era Twin Study of Aging who were cognitively unimpaired at baseline (mean age = 56 years; range = 51-60). Individuals with both high thickness/volume signatures and high MD signatures at baseline had lower cortical thickness/volume in AD signature regions and lower episodic memory performance 12 years later compared to those with high thickness/volume and low MD signatures at baseline. Groups did not differ in level of young adult cognitive reserve. Our findings are in line with a biphasic model in which increased cortical thickness may precede future decline and establish the value of examining cortical MD alongside cortical thickness to identify subgroups with differential risk for poorer brain and cognitive outcomes.

BackgroundComposite scores of magnetic resonance imaging-derived metrics in brain regions associated with Alzheimer's disease (AD), commonly termed AD signatures, have been developed to distinguish early AD-related atrophy from normal age-associated changes. Diffusion-based gray matter signatures may be more sensitive to early AD-related changes compared with thickness/volume-based signatures, demonstrating their potential clinical utility. The timing of early (i.e., midlife) changes in AD signatures from different modalities and whether diffusion- and thickness/volume-based signatures each capture unique AD-related phenotypic or genetic information remains unknown.MethodsOur validated thickness/volume signature, our novel mean diffusivity (MD) signature, and a magnetic resonance imaging-derived measure of brain age were used in biometrical analyses to examine genetic and environmental influences on the measures as well as phenotypic and genetic relationships between measures over 12 years. Participants were 736 men from 3 waves of the Vietnam Era Twin Study of Aging (VETSA) (baseline/wave 1: mean age [years] = 56.1, SD = 2.6, range = 51.1-60.2). Subsequent waves occurred at approximately 5.7-year intervals.ResultsMD and thickness/volume signatures were highly heritable (56%-72%). Baseline MD signatures predicted thickness/volume signatures over a decade later, but baseline thickness/volume signatures showed a significantly weaker relationship with future MD signatures. AD signatures and brain age were correlated, but each measure captured unique phenotypic and genetic variance.ConclusionsCortical MD and thickness/volume AD signatures are heritable, and each signature captures unique variance that is also not explained by brain age. Moreover, results are in line with changes in MD emerging before changes in cortical thickness, underscoring the utility of MD as a very early predictor of AD risk.

Marine heatwaves cause widespread environmental, biological, and socio-economic impacts, placing them at the forefront of 21st-century management challenges. However, heatwaves vary in intensity and evolution, and a paucity of information on how this variability impacts marine species limits our ability to proactively manage for these extreme events. Here, we model the effects of four recent heatwaves (2014, 2015, 2019, 2020) in the Northeastern Pacific on the distributions of 14 top predator species of ecological, cultural, and commercial importance. Predicted responses were highly variable across species and heatwaves, ranging from near total loss of habitat to a two-fold increase. Heatwaves rapidly altered political bio-geographies, with up to 10% of predicted habitat across all species shifting jurisdictions during individual heatwaves. The variability in predicted responses across species and heatwaves portends the need for novel management solutions that can rapidly respond to extreme climate events. As proof-of-concept, we developed an operational dynamic ocean management tool that predicts predator distributions and responses to extreme conditions in near real-time.