Fiscal policies and car choices in Italy and Norway: A scenario analysis based on a stated-preference survey

Norwegian and Italian car drivers make very different car choices. This paper investigates the influence of fiscal policies on car buyers’ choices, using data collected from a stated preference survey conducted in 2021. After estimating a joint random parameter logit model, we simulated the market shares of five car powertrains under three scenarios: “Italian car buyers face the same net purchase car prices and fuel\electricity costs as the Norwegian car drivers and vice versa”, “Italy adopts the Norwegian registration tax”, and “Both Italy and Norway adopt a social cost internalizing registration tax”. The results indicate that Italian car users are reluctant to switch to battery electric cars (BEVs). They would choose BEVs more frequently in the three scenarios envisaged but without reaching the corresponding Norwegian levels. If Italy would adopt the Norwegian registration tax system, BEVs’ market share would gain 5.4 percentage points relative to the baseline scenario, while under the social cost internalizing scenario, BEVs’ market share would improve by 3.4 and PHEVs’ one by 0.2 percentage points. On the contrary, Norwegians are BEV-oriented and would comparatively preserve a high BEV share. In the social cost internalization scenario, the BEV share relative to the baseline scenario would decrease by 7.2 percentage points, petrol cars would gain 1.2, HEVs 2.9, PHEVs 3.4, and diesel cars would lose 0.3 percentage points. In general, there seems to be a lock-in or path dependence effect that limits BEV penetration in Italy and prevents the decline of the BEV share in Norway

Bioarchaeological and palaeogenomic portrait of two Pompeians that died during the eruption of Vesuvius in 79 AD

The archaeological site of Pompeii is one of the 54 UNESCO World Heritage sites in Italy, thanks to its uniqueness: the town was completely destroyed and buried by a Vesuvius’ eruption in 79 AD. In this work, we present a multidisciplinary approach with bioarchaeological and palaeogenomic analyses of two Pompeian human remains from the Casa del Fabbro. We have been able to characterize the genetic profle of the frst Pompeian’ genome, which has strong afnities with the surrounding central Italian population from the Roman Imperial Age. Our fndings suggest that, despite the extensive connection between Rome and other Mediterranean populations, a noticeable degree of genetic homogeneity exists in the Italian peninsula at that time. Moreover, palaeopathological analyses identifed the presence of spinal tuberculosis and we further investigated the presence of ancient DNA from Mycobacterium tuberculosis. In conclusion, our study demonstrates the power of a combined approach to investigate ancient humans and confrms the possibility to retrieve ancient DNA from Pompeii human remains. Our initial fndings provide a foundation to promote an intensive and extensive paleogenetic analysis in order to reconstruct the genetic history of population from Pompeii, a unique archaeological site

Opa1 overexpression ameliorates the phenotype of two mitochondrial disease mouse models

SummaryIncreased levels of the mitochondria-shaping protein Opa1 improve respiratory chain efficiency and protect from tissue damage, suggesting that it could be an attractive target to counteract mitochondrial dysfunction. Here we show that Opa1 overexpression ameliorates two mouse models of defective mitochondrial bioenergetics. The offspring from crosses of a constitutive knockout for the structural complex I component Ndufs4 (Ndufs4−/−), and of a muscle-specific conditional knockout for the complex IV assembly factor Cox15 (Cox15sm/sm), with Opa1 transgenic (Opa1tg) mice showed improved motor skills and respiratory chain activities compared to the naive, non-Opa1-overexpressing, models. While the amelioration was modest in Ndufs4−/−::Opa1tg mice, correction of cristae ultrastructure and mitochondrial respiration, improvement of motor performance and prolongation of lifespan were remarkable in Cox15sm/sm::Opa1tg mice. Mechanistically, respiratory chain supercomplexes were increased in Cox15sm/sm::Opa1tg mice, and residual monomeric complex IV was stabilized. In conclusion, cristae shape amelioration by controlled Opa1 overexpression improves two mouse models of mitochondrial disease

Dysfunctional mitochondria accumulate in a skeletal muscle knockout model of Smn1, the causal gene of spinal muscular atrophy

The approved gene therapies for spinal muscular atrophy (SMA), caused by loss of survival motor neuron 1 (SMN1), greatly ameliorate SMA natural history but are not curative. These therapies primarily target motor neurons, but SMN1 loss has detrimental effects beyond motor neurons and especially in muscle. Here we show that SMN loss in mouse skeletal muscle leads to accumulation of dysfunctional mitochondria. Expression profiling of single myofibers from a muscle specific Smn1 knockout mouse model revealed down-regulation of mitochondrial and lysosomal genes. Albeit levels of proteins that mark mitochondria for mitophagy were increased, morphologically deranged mitochondria with impaired complex I and IV activity and respiration and that produced excess reactive oxygen species accumulated in Smn1 knockout muscles, because of the lysosomal dysfunction highlighted by the transcriptional profiling. Amniotic fluid stem cells transplantation that corrects the SMN knockout mouse myopathic phenotype restored mitochondrial morphology and expression of mitochondrial genes. Thus, targeting muscle mitochondrial dysfunction in SMA may complement the current gene therapy

The endogenous caspase-8 inhibitor c-FLIPL regulates ER morphology and crosstalk with mitochondria

Components of the death receptors-mediated pathways like caspase-8 have been identified in complexes at intracellular membranes to spatially restrict the processing of local targets. In this study, we report that the long isoform of the cellular FLICE-inhibitory protein (c-FLIPL), a well- known inhibitor of the extrinsic cell death initiator caspase-8, localizes at the endoplasmic reticulum (ER) and mitochondria-associated membranes (MAMs). ER morphology was disrupted and ER Ca2+-release as well as ER-mitochondria tethering were decreased in c-FLIP-/- mouse embryonic fibroblasts (MEFs). Mechanistically, c-FLIP ablation resulted in enhanced basal caspase-8 activation and in caspase-mediated processing of the ER-shaping protein reticulon-4 (RTN4) that was corrected by re-introduction of c-FLIPL and caspase inhibition, resulting in the recovery of a normal ER morphology and ER-mitochondria juxtaposition. Thus, the caspase-8 inhibitor c-FLIPL emerges as a component of the MAMs signaling platforms, where caspases appear to regulate ER morphology and ER-mitochondria crosstalk by impinging on ER-shaping proteins like the RTN4

Impaired Mitochondrial ATP Production Downregulates Wnt Signaling via ER Stress Induction

Wnt signaling affects fundamental development pathways and, if aberrantly activated, promotes the development of cancers. Wnt signaling is modulated by different factors, but whether the mitochondria! energetic state affects Wnt signaling is unknown. Here, we show that sublethal concentrations of different compounds that decrease mitochondrial ATP production specifically downregulate Wnt/beta-catenin signaling in vitro in colon cancer cells and in vivo in zebrafish reporter lines. Accordingly, fibroblasts from a GRACILE syndrome patient and a generated zebrafish model lead to reduced Wnt signaling. We identify a mitochondria-Wnt signaling axis whereby a decrease in mitochondria! ATP reduces calcium uptake into the endoplasmic reticulum (ER), leading to endoplasmic reticulum stress and to impaired Wnt signaling. In turn, the recovery of the ATP level or the inhibition of endoplasmic reticulum stress restores Wnt activity. These findings reveal a mechanism that links mitochondria! energetic metabolism to the control of the Wnt pathway that may be beneficial against several pathologie

Impaired Mitochondrial ATP Production Downregulates Wnt Signaling via ER Stress Induction

Wnt signaling affects fundamental development pathways and, if aberrantly activated, promotes the development of cancers. Wnt signaling is modulated by different factors, but whether the mitochondria! energetic state affects Wnt signaling is unknown. Here, we show that sublethal concentrations of different compounds that decrease mitochondrial ATP production specifically downregulate Wnt/beta-catenin signaling in vitro in colon cancer cells and in vivo in zebrafish reporter lines. Accordingly, fibroblasts from a GRACILE syndrome patient and a generated zebrafish model lead to reduced Wnt signaling. We identify a mitochondria-Wnt signaling axis whereby a decrease in mitochondria! ATP reduces calcium uptake into the endoplasmic reticulum (ER), leading to endoplasmic reticulum stress and to impaired Wnt signaling. In turn, the recovery of the ATP level or the inhibition of endoplasmic reticulum stress restores Wnt activity. These findings reveal a mechanism that links mitochondria! energetic metabolism to the control of the Wnt pathway that may be beneficial against several pathologie

Bacterial porin disrupts mitochondrial membrane potential and sensitizes host cells to apoptosis

The bacterial PorB porin, an ATP-binding beta-barrel protein of pathogenic Neisseria gonorrhoeae, triggers host cell apoptosis by an unknown mechanism. PorB is targeted to and imported by host cell mitochondria, causing the breakdown of the mitochondrial membrane potential (delta psi m). Here, we show that PorB induces the condensation of the mitochondrial matrix and the loss of cristae structures, sensitizing cells to the induction of apoptosis via signaling pathways activated by BH3-only proteins. PorB is imported into mitochondria through the general translocase TOM but, unexpectedly, is not recognized by the SAM sorting machinery, usually required for the assembly of beta-barrel proteins in the mitochondrial outer membrane. PorB integrates into the mitochondrial inner membrane, leading to the breakdown of delta psi m. The PorB channel is regulated by nucleotides and an isogenic PorB mutant defective in ATP-binding failed to induce delta psi m loss and apoptosis, demonstrating that dissipation of delta psi m is a requirement for cell death caused by neisserial infection