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Paltrinieri, S.

Publications and source records attributed to Paltrinieri, S..

3 recordsLinked to original sources

Replication-independent eviction of H2B.8 reveals chromatin reprogramming during seed imbibition

The transition from seed to seedling involves major changes in nuclear organization and gene expression, yet the extent to which this developmental transition requires chromatin reprogramming remains largely unexplored. Here, we report that Arabidopsis dry seed embryos accumulate the histone variant H2B.8, which contributes to higher-order chromatin organization by forming spatial clusters that structure the 3D nuclear space. H2B.8 forms heterotypic nucleosomes at euchromatic transposons and lowly expressed genes and, during imbibition, modulates the transcriptional activation of a subset of these genes. Imbibition triggers a decrease in H2B.8 transcripts and the eviction of H2B.8 proteins in a process that operates independently of DNA replication but requires protein translation and de novo transcription. Histone eviction is not limited to H2B.8 as imbibition also induces the turnover of the H3.3 histone variant, thereby initiating a broad, replication-independent chromatin reprogramming process. These findings highlight a fundamental mechanism of epigenetic regulation during early plant development.

molecular biology↗

Cholesterol-laden brain-permeable nanoparticles support long-lasting cognitive recovery and motor amelioration in the slow-progressing zQ175DN mouse model of Huntington's Disease

Evidence that Huntingtons disease (HD) is characterized by impaired cholesterol biosynthesis in the brain has led to strategies to increase its level in the brain of the rapidly progressing R6/2 mouse model, with a positive therapeutic outcome. Here we tested the long-term efficacy of chronic administration of cholesterol to the brain of the slowly progressing zQ175DN knock-in HD mice in preventing ("early treatment") or reversing ("late treatment") HD symptoms. To do this we used the most advanced formulation of cholesterol loaded brain-permeable nanoparticles (NPs), termed hybrid-g7-NPs-chol, which were injected intraperitoneally. We show that one cycle of treatment with hybrid-g7-NPs-chol, administered in the presymptomatic ("early treatment") or symptomatic ("late treatment") stages is sufficient to normalize cognitive defects up to 5 months, as well as to improve other behavioral and neuropathological parameters. A multiple cycle treatment combining both early and late treatments ("2 cycle treatment") lasting 6 months generates therapeutic effects for more than 11 months, without severe adverse reactions. Sustained cholesterol delivery to the brain of zQ175DN mice also reduces mutant Huntingtin aggregates in both the striatum and cortex and completely normalizes synaptic communication in the striatal medium spiny neurons compared to saline-treated HD mice. Furthermore, through a meta-analysis of published and current data, we demonstrated the power of hybrid-g7-NPs-chol and other strategies able to increase brain cholesterol biosynthesis, to reverse cognitive decline and counteract the formation of mutant Huntingtin aggregates. These results demonstrate that cholesterol delivery via brain-permeable NPs is a therapeutic option to sustainably reverse HD-related behavioral decline and neuropathological signs over time, highlighting the therapeutic potential of cholesterol-based strategies in HD patients.

neuroscience↗

Evidence of exposure to SARS-CoV-2 in cats and dogs from households in Italy

SARS-CoV-2 originated in animals and is now easily transmitted between people. Sporadic detection of natural cases in animals alongside successful experimental infections of pets, such as cats, ferrets and dogs, raises questions about the susceptibility of animals under natural conditions of pet ownership. Here we report a large-scale study to assess SARS-CoV-2 infection in 817 companion animals living in northern Italy, sampled at a time of frequent human infection. No animals tested PCR positive. However, 3.4% of dogs and 3.9% of cats had measurable SARS-CoV-2 neutralizing antibody titers, with dogs from COVID-19 positive households being significantly more likely to test positive than those from COVID-19 negative households. Understanding risk factors associated with this and their potential to infect other species requires urgent investigation. One Sentence SummarySARS-CoV-2 antibodies in pets from Italy.

microbiology↗