TGF beta type II receptor signaling controls Schwann cell death and proliferation in developing nerves

During development, Schwann cell numbers are precisely adjusted to match the number of axons. It is essentially unknown which growth factors or receptors carry out this important control in vivo. Here, we tested whether the type II transforming growth factor (TGF)beta receptor has a role in this process. We generated a conditional knock-out mouse in which the type II TGF beta receptor is specifically ablated only in Schwann cells. Inactivation of the receptor, evident at least from embryonic day 18, resulted in suppressed Schwann cell death in normally developing and injured nerves. Notably, the mutants also showed a strong reduction in Schwann cell proliferation. Consequently, Schwann cell numbers in wild-type and mutant nerves remained similar. Lack of TGF beta signaling did not appear to affect other processes in which TGF beta had been implicated previously, including myelination and response of adult nerves to injury. This is the first in vivo evidence for a growth factor receptor involved in promoting Schwann cell division during development and the first genetic evidence for a receptor that controls normal developmental Schwann cell death

High-Throughput and Cost-Effective Characterization of Induced Pluripotent Stem Cells.

Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) offers the possibility of studying the molecular mechanisms underlying human diseases in cell types difficult to extract from living patients, such as neurons and cardiomyocytes. To date, studies have been published that use small panels of iPSC-derived cell lines to study monogenic diseases. However, to study complex diseases, where the genetic variation underlying the disorder is unknown, a sizable number of patient-specific iPSC lines and controls need to be generated. Currently the methods for deriving and characterizing iPSCs are time consuming, expensive, and, in some cases, descriptive but not quantitative. Here we set out to develop a set of simple methods that reduce cost and increase throughput in the characterization of iPSC lines. Specifically, we outline methods for high-throughput quantification of surface markers, gene expression analysis of in vitro differentiation potential, and evaluation of karyotype with markedly reduced cost

Attenuation of choroidal tickness in patients with Alzheimer disease: evidence from an Italian prospective study

INTRODUCTION: To compare the 12-month choroidal thickness (CT) change between Alzheimer disease (AD) patients and normal subjects. METHODS: In this prospective, observational study, 39 patients with a diagnosis of mild to moderate AD and 39 age-matched control subjects were included. All the subjects underwent neuropsychological (Mini Mental State Examination, Alzheimer disease Assessment Scale-Cognitive Subscale, and the Clinical Dementia Rating Scale) and ophthalmological evaluation, including spectral domain optical coherence tomography, at baseline and after 12 months. CT was measured manually using the caliper tool of the optical coherence tomography device. RESULTS: After 12 months, AD patients had a greater reduction of CT than controls (P≤0.05, adjusted for baseline CT, age, sex, axial length, and smoking). DISCUSSION: CT in patients with AD showed a rate of thinning greater than what could be expected during the natural course of aging

Geochemical characteristics and mantle sources of the Oligo-Miocene primitive basalts from Sardinia: The role of subduction components.

During the Oligo-Miocene, the Island of Sardinia was covered by the products of voluminous magmatic activity, with a typical subduction-related signature. The mafic rocks of the Montresta (north) and Arcuentu (south) volcanic districts include primitive high MgO basalts whose trace element and Sr-, Nd- and Pb-isotope compositions constrain the nature and role of subduction-related components in the Tertiary Sardinian volcanism. The geochemical and isotopic data require an approximate degree of partial melting of 15% of a MORB-like depleted mantle prior to enrichment, and the input of two subduction components in the mantle wedge consisting of fluids from subducted oceanic crust (altered MORB) and fluids from subducted sediments. Ratios among trace elements which are variably compatible with fluid and melt phases (i.e. Th/Pb, Th/Nd and Sr/Nd) exclude the contribution of melts from the subducted slab. Models based on isotopic ratios indicate that the pre-subduction depleted mantle source of Sardinia magmas was enriched by 0.1-0.5% MORB fluid and less than 0.1% sediment fluid. The geochemical and isotopic compositions of the Montresta volcanic rocks are homogeneous, whereas those of the Arcuentu show quite heterogeneous characters, suggesting variations in mantle source over the long time-span (about 13 Ma) of volcanic activity in this district

Facing the blockchain endpoint vulnerability, an SGX-based solution for secure eHealth auditing

According to McAfee Labs, even in 2019, the eHealth sector is confirmed as one of the most critical in terms of cybersecurity incidents. It is estimated that more than 176 million patient records were target of attacks between 2009 and 2017, and with a single attack, in 2018, more than 1.4 million patient records were affected at UnityPoint Health. To cope with such a dramatic situation, one of the main strategic priority in the eHealth field is represented by the adoption of Blockchain. Specifically, according to a Deloittes survey, 55% of healthcare executives believe that blockchain technology will disrupt the healthcare industry. Unfortunately, while blockchain provides a valuable tool for enhancing the security of health applications and related data, it cannot be assumed as a panacea for data security. As an example, the so-called Endpoint Vulnerability issue is a well-known problem of Blockchain-based solutions: in such a case the attacker successful in gaining control of the end-point can tamper data off-chain during its generation and/or before it is sent to the chain. In this paper, we face such an issue by shielding the endpoint through the Intel Software Guard eXtension (SGX) technology. We demonstrate our solution for an auditing software belonging to the European eHealth management system (namely OpenNCP). We also discuss how our solution can be generalized to any other Blockchain-based solution. Finally, an experimental evaluation has been conducted to prove the actual feasibility of the proposed solution under the requirements of the real eHealth system

A resilient architecture for forensic storage of events in critical infrastructures

In Critical Infrastructures, forensic analysis of stored events is an essential task when a security breach occurs. The goal of forensic analysis is to provide evidence to be used as valid proofs in a legal proceeding. So, it is very important to ensure the integrity of the events stored in order to perform a correct forensic analysis. Today, most of the SIEMs used to protect the Critical Infrastructures sign the security events with RSA classic algorithm in order to ensure their integrity. The signed security events cannot be admissible as evidence if the secret key is compromised, or when the module responsible for signing operations is down for any reason. In this paper a new architecture that overcomes these limitations has been proposed. Experimental tests show the performance of our architecture and the high resilience in faulty situations, i.e. some nodes are under attack

An intrusion and fault tolerant forensic storage for a SIEM system

Current Security Information and Events Management (SIEM) solutions lack a data storage facility which is secure enough - i.e. stored events related to security incidents cannot be forged and are always available - that it can be used for forensic purposes. Forensic storage used by current SIEM solutions uses traditional RSA algorithm to sign the security events. In this paper we have analyzed the limits of current forensic storages, and we have proposed an architecture for forensic storage, implementing a threshold-based variant of the RSA algorithm, that outperforms state of the art SIEM solutions in terms of intrusion- and fault-tolerance. We show by experiments that our forensic storage works correctly even in the presence of cyber-attacks, although with a performance penalty. We also conduct an experimental campaign to evaluate the performance cost of the proposed scheme as a function of the threshold

Fosamprenavir treatment in a highly active antiretroviral therapy schedule induces a HCV-RNA decrease and a Th1 network boost in HIV/HCV-coinfected patients

AbstractHIV/HCV co-infected naïve patients (four females and six males) were evaluated for their response to the following treatment schedule: [(AZT 300 mg + 3TC 300 mg twice daily) + (fosamprenavir 700 mg twice daily) + (RTV 100 mg)]. CD3+/CD4+ T cells, interferon-γ (INF-γ) and interleukin-4 (IL-4) HCV-specific response, viral loads and transaminase levels were evaluated at time 0, and after 1, 3 and 6 months of therapy (T0, T1, T3, and T6 respectively). HIV-RNA, HCV-RNA and transaminases decreased at T1 and T3 compared with T0 (Mann–Whitney p <0.001, p <0.01 and p <0.01, respectively). At all time points, CD4+ and HCV-specific INF-γ responses were higher (p <0.001; p <0.001), and IL-4 lower (p <0.01) after treatment. At T6, HCV-RNA was only negative in four out of ten patients whereas all had normal transaminase levels. These findings indicate that HAART treatment including fosamprenavir is able to activate a Th1 network in HIV/HCV co-infected patients. Moreover, these results, to be confirmed by larger cohort follow-up studies, suggest that this protease inhibitor could have potential implications for the treatment of chronic hepatitis C in HIV–positive patients

Boom‐bust dynamics in biological invasions: towards an improved application of the concept

Boom‐bust dynamics – the rise of a population to outbreak levels, followed by a dramatic decline – have been associated with biological invasions and offered as a reason not to manage troublesome invaders. However, boom‐bust dynamics rarely have been critically defined, analyzed, or interpreted. Here, we define boom‐bust dynamics and provide specific suggestions for improving the application of the boom‐bust concept. Boom‐bust dynamics can arise from many causes, some closely associated with invasions, but others occurring across a wide range of ecological settings, especially when environmental conditions are changing rapidly. As a result, it is difficult to infer cause or predict future trajectories merely by observing the dynamic. We use tests with simulated data to show that a common metric for detecting and describing boom‐bust dynamics, decline from an observed peak to a subsequent trough, tends to severely overestimate the frequency and severity of busts, and should be used cautiously if at all. We review and test other metrics that are better suited to describe boom‐bust dynamics. Understanding the frequency and importance of boom‐bust dynamics requires empirical studies of large, representative, long‐term data sets that use clear definitions of boom‐bust, appropriate analytical methods, and careful interpretations