Amyloid prefibrillar oligomers: The surprising commonalities in their structure and activity

It has been proposed that a "common core" of pathologic pathways exists for the large family of amyloid-associated neurodegenerations, including Alzheimer's, Parkinson's, type II diabetes and Creutzfeldt-Jacob's Disease. Aggregates of the involved proteins, independently from their primary sequence, induced neuron membrane permeabilization able to trigger an abnormal Ca2+ influx leading to synaptotoxicity, resulting in reduced expression of synaptic proteins and impaired synaptic transmission. Emerging evidence is now focusing on low-molecular-weight prefibrillar oligomers (PFOs), which mimic bacterial pore-forming toxins that form well-ordered oligomeric membrane-spanning pores. At the same time, the neuron membrane composition and its chemical microenvironment seem to play a pivotal role. In fact, the brain of AD patients contains increased fractions of anionic lipids able to favor cationic influx. However, up to now the existence of a specific "common structure" of the toxic aggregate, and a "common mechanism" by which it induces neuronal damage, synaptotoxicity and impaired synaptic transmission, is still an open hypothesis. In this review, we gathered information concerning this hypothesis, focusing on the proteins linked to several amyloid diseases. We noted commonalities in their structure and membrane activity, and their ability to induce Ca2+ influx, neurotoxicity, synaptotoxicity and impaired synaptic transmission

Pre-Production and Quality Assurance of the Mu2e Calorimeter Silicon Photomultipliers

The Mu2e electromagnetic calorimeter has to provide precise information on energy, time and position for $\sim$100 MeV electrons. It is composed of 1348 un-doped CsI crystals, each coupled to two large area Silicon Photomultipliers (SiPMs). A modular and custom SiPM layout consisting of a 3$\times$2 array of 6$\times$6 mm$^2$ UV-extended monolithic SiPMs has been developed to fulfill the Mu2e calorimeter requirements and a pre-production of 150 prototypes has been procured by three international firms (Hamamatsu, SensL and Advansid). A detailed quality assurance process has been carried out on this first batch of photosensors: the breakdown voltage, the gain, the quenching time, the dark current and the Photon Detection Efficiency (PDE) have been determined for each monolithic cell of each SiPMs array. One sample for each vendor has been exposed to a neutron fluency up to $\sim$8.5~$\times$~10$^{11}$ 1 MeV (Si) eq. n/cm$^{2}$ and a linear increase of the dark current up to tens of mA has been observed. Others 5 samples for each vendor have undergone an accelerated aging in order to verify a Mean Time To Failure (MTTF) higher than $\sim$10$^{6}$ hours.Comment: NDIP 2017 - New Developments In Photodetection, 3-7 July 2017, Tours (France

Epidermolysis Bullosa in children: the central role of the pediatrician

Epidermolysis bullosa (EB) is a severe hereditary disease characterized by defective epithelial adhesion causing mucocutaneous fragility. The major types are EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB) and more than 35 EB subtypes. Another very rare type of EB is Kindler EB (KEB). Clinically, it is a very heterogeneous disease which ranges from localized to extensive skin lesions with frequent multisystem extra cutaneous involvement. The role of a pediatrician-dermatologist cooperation within a multidisciplinary team is fundamental for both the diagnosis and management contributing to these patients' better life expectancy. Aim of this study is to describe clinical and laboratory characteristics of the main EB subtypes focusing on nutritional and gastrointestinal aspects, providing information to aid the paediatric management of children with EB. This retrospective study reviewed the cases of 160 pediatric EB patients (76 male and 84 female): 31 patients affected by EBS (mean age +/- SD: 4.37 +/- 7.14), 21 patients affected by JEB (mean age +/- SD: 9.26 +/- 17.30) and 108 with DEB (mean age +/- SD: 11.61 +/- 13.48). All patients were admitted at the Bambino Gesu Children's Hospital in Rome, between June 2005 to June 2020. The reduced gastrointestinal absorption, chronic losses, esophageal stenosis and chronic inflammatory state, represent the basis of nutritional problems of EB patients. In particular, anemia represents one of the most important complications of DEB patients which could require transfusion-dependent patterns. Malnutrition, vitamin deficiencies and anemia have been related to growth delay in EB patients. A specific diet with a balance of all macronutrients is required and improving caloric intake with sugar limitations is fundamental to prevent dental caries and tooth decay typical of EB patients. While sepsis proved to be the major cause of morbidity and mortality in younger patients, squamous cell carcinoma was mostly observed in older patients, especially those affected by DEB. Patients with EB require regular monitoring for complications and sequelae with a frequency of evaluations which varies based on age and EB subtypes. Cooperation among medical teams involving paediatricians, dermatologists, specialist clinicians including nutritionists such as families and patient's association is fundamental to approach the disease and improve the quality of life of these patients

naevoid basal cell carcinoma syndrome in a 22 month old child presenting with multiple basal cell carcinomas and a fetal rhabdomyoma

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Quality Assurance on a custom SiPMs array for the Mu2e experiment

The Mu2e experiment at Fermilab will search for the coherent $\mu \to e$ conversion on aluminum atoms. The detector system consists of a straw tube tracker and a crystal calorimeter. A pre-production of 150 Silicon Photomultiplier arrays for the Mu2e calorimeter has been procured. A detailed quality assur- ance has been carried out on each SiPM for the determination of its own operation voltage, gain, dark current and PDE. The measurement of the mean-time-to-failure for a small random sample of the pro-production group has been also completed as well as the determination of the dark current increase as a function of the ioninizing and non-ioninizing dose.Comment: 4 pages, 10 figures, conference proceeding for NSS-MIC 201