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Sacchi, A.

Publications and source records attributed to Sacchi, A..

2 recordsLinked to original sources

Areas of high risk for mammalian biodiversity and Nature's Contributions to People under global warming

Climate change has reached unprecedented levels, causing frequent extreme events like droughts and fires. Combined with land-use change, this crisis has impacted biodiversity, increasing species extinction rates, and Natures Contributions to People (NCP), degrading ecosystem functions. We developed a comparative extinction risk model for mammals sensitive to fire, drought, and extreme temperatures, utilizing a Random Forest algorithm to predict future extinction probabilities under different climatic scenarios. We then identified high-risk areas for both mammals and NCP under global warming, aiming to find synergies between biodiversity conservation and NCP preservation. Our results show that 288 out of 454 species (63%) face an increased extinction risk (mean increase 0.28), while 166 species (37%) show a predicted decrease (mean decrease 0.20) under the extreme "Fossil-fueled development" scenario. The highest risk increase was observed in Malaysia, Western Indonesia, Madagascar, Eastern Australia, and South Africa, under both pessimistic and optimistic ("Sustainability") scenarios. These regions also represent high-risk areas for several NCP: freshwater regulation, air quality, mitigation of extreme events. Preserving these high-risk regions is crucial for reducing habitat loss and human-induced extinctions. Safeguarding these ecosystems, which provide vital contributions like carbon storage, clean water, and extreme fire mitigation, should be a high priority. These regions warrant targeted policy and management interventions, including sustainable land-use practices and climate adaptation actions, to benefit both biodiversity and human well-being.

ecology↗

Reversal of pathologic changes in fibroblasts from Niemann-Pick type C disease patients by inhibition of bromodomain and extraterminal proteins

Inborn errors of lysosomal function often provoke disorders presenting highly variable onset, diverse visceral, neurologic and psychiatric symptoms and reduced life spans. A prime example is Niemann-Pick type C disease (NPCD). At present, therapeutic options are limited to palliative care and disease-modifying drugs, and there is a need for new treatments. Here, we explored bromodomain and extra-terminal domain (BET) proteins as a new drug target for NPCD using patient-derived skin fibroblasts. Treatment of cells with JQ1, a prototype BET protein inhibitor, enhanced the level of NPC1 protein, diminished lysosomal expansion and cholesterol accumulation, and induced extracellular release of lysosomal components in a dose- and time-dependent manner. The effect of JQ1 on protein levels was largely independent from the patient line tested, but the extent of cholesterol reduction varied in a line-dependent manner. Lastly, JQ1 enhanced and reduced cholesterol accumulation induced by inhibition of NPC1 activity and of histone deacetylases, respectively. Taken together, our results provide further evidence for epigenetic regulation of cellular NPC1 levels and cholesterol homeostasis. Pharmacologic inhibition of bromodomain proteins should be explored as candidate therapeutic approach for NPCD and as a tool to understand basic mechanisms of lysosomal function and lipid metabolism.

cell biology↗