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Guglielmetti, C.

Publications and source records attributed to Guglielmetti, C..

3 recordsLinked to original sources

AA-amyloidosis in cats (Felis catus) housed in shelters

Systemic AA-amyloidosis is a protein-misfolding disease that is characterized by fibril deposition of serum amyloid-A protein (SAA) in several organs in humans and many animal species. Fibril deposits originate from abnormally high serum levels of SAA during chronic inflammation. In domestic short-hair cats, AA-amyloidosis has only been anecdotally reported and is considered a rare disease. Here we report that an astonishing 57-73% of early deceased short-hair cats kept in three independent shelters suffer from amyloid deposition in the liver, spleen, or kidney. Histopathology and mass spectrometry of post-mortem extracted deposits identified SAA as the major protein source. The duration of stay in the shelters was positively associated with a histological score of AA-amyloidosis (B=0.026, CI95%=0.007-0.046; p=0.010). Presence of SAA fragments in bile secretions raises the possibility of fecal-oral transmission of the disease.

pathology↗

Open Data Commons for Preclinical Traumatic Brain Injury Research: Empowering Data Sharing and Big Data Analytics

Traumatic brain injury (TBI) is a major unsolved public health problem worldwide with considerable preclinical research dedicated to recapitulating clinical TBI, deciphering the underlying pathophysiology, and developing therapeutics. However, the heterogeneity of clinical TBI and correspondingly in preclinical studies have made translation from bench to bedside difficult. Here, we present the potential of data sharing, data aggregation, and multivariate analytics to integrate heterogeneity and empower researchers. We introduce the Open Data Commons for Traumatic Brain Injury (ODC-TBI.org) as a user-centered web platform and cloudbased repository focused on preclinical TBI research that enables data citation with persistent identifiers, promotes data element harmonization, and follows FAIR data sharing principles. Importantly, the ODC-TBI implements data sharing at the level of individual subjects, thus enabling data reuse for granular big data analytics and data-hungry machine learning approaches. We provide use cases applying descriptive analytics and unsupervised machine learning on pooled ODC-TBI data. Descriptive statistics included subject-level data for 11 published papers (N = 1250 subjects) representing six distinct TBI models across mice and rats (implementing controlled cortical impact, closed head injury, fluid percussion injury, and CHIMERA TBI modalities). We performed principal component analysis (PCA) on cohorts of animals combined through the ODC-TBI to identify persistent inflammatory patterns across different experimental designs. Our workflow ultimately improved the sensitivity of our analyses in uncovering patterns of pro- vs anti-inflammation and oxidative stress without the multiple testing problems of univariate analyses. As the practice of open data becomes increasingly required by the scientific community, ODC-TBI provides a foundation that creates new scientific opportunities for researchers and their work, facilitates multi-dataset and multidimensional analytics, and drives collaboration across molecular and computational biologists to bridge preclinical research to the clinic.

neuroscience↗

Imaging toxin-induced neuroinflammation in mice using hyperpolarized 13C magnetic resonance spectroscopy

Lipopolysaccharide (LPS) is a commonly used agent for induction of neuroinflammation in preclinical studies. Upon injection, LPS causes activation of microglia and astrocytes, whose metabolism alters to favor glycolysis. Assessing in vivo neuroinflammation and its modulation following therapy remains challenging, and new non-invasive methods allowing for longitudinal monitoring would be greatly valuable. Hyperpolarized (HP) 13C magnetic resonance spectroscopy (MRS) is a promising technique for assessing in vivo metabolism. In addition to applications in oncology, the most commonly used probe of [1-13C] pyruvate has shown potential in assessing neuroinflammation-linked metabolism in mouse models of multiple sclerosis and traumatic brain injury. Here, we wished to investigate LPS-induced neuroinflammatory changes using HP [1-13C] pyruvate and HP 13C urea.\n\n2D chemical shift imaging following simultaneous intravenous injection of HP [1-13C] pyruvate and HP 13C urea was performed at baseline (day 0), day 3 and day 7 post intracranial injection of LPS (n=6) or saline (n=5). Immunofluorescence (IF) analyses were performed for Iba1 (resting and activated microglia/macrophages), GFAP (resting and reactive astrocytes) and CD68 (activated microglia/macrophages).\n\nA significant increase in HP [1-13C] lactate production was observed in the injected (ipsilateral) side at 3 and 7 days of the LPS-treated mouse brain, but not in either the contralateral side or saline-injected animals. HP 13C lactate/pyruvate ratio, without and with normalization to urea, was also significantly increased in the ipsilateral LPS-injected brain at 7 days compared to baseline. IF analyses showed a significant increase in CD68 and GFAP at 3 days, followed by increased numbers of Iba1 and GFAP positive cells at 7 days post-LPS injection.\n\nIn conclusion, we can detect LPS-induced changes in the mouse brain using HP 13C MRS, in alignment with increased numbers of microglia/macrophages and astrocytes. This study demonstrates that HP 13C spectroscopy holds much potential for providing non-invasive information on neuroinflammation.

immunology↗