Search

The Forkhead box P2 (FOXP2) is an evolutionary conserved transcription factor involved in the maintenance of neuronal networks, implicated in language disorders. Some evidence suggests a possible link between FOXP2 genetic variability and frontotemporal dementia (FTD) pathology and related endophenotypes. To shed light on this issue, we analysed the association between single-nucleotide polymorphisms (SNPs) in FOXP2 and FTD in 113 patients and 223 healthy controls. In addition, we investigated SNPs in two putative targets of FOXP2, CNTNAP2, Contactin-associated protein-like 2 and PRNP, prion protein genes. Overall, 27 SNPs were selected by a tagging approach. FOXP2-rs17213159-C/T resulted associated with disease risk (OR = 2.16, P = 0.0004), as well as with age at onset and severity of dementia. Other FOXP2 markers were associated with semantic and phonological fluency scores, cognitive levels (MMSE) and neuropsychological tests. Associations with language, cognitive and brain atrophy measures were found with CNTNAP2 and PRNP genetic variability. Overall, although preliminary, results here presented suggest an influence of regulatory pathways centred on FOXP2 as a molecular background of FTD affecting neurological function of multiple brain areas.

There has been substantial growth in postgraduate coursework study in Australia since moves towards deregulation began in the early 1990s. This growth in postgraduate coursework education has brought benefits for both institutions and individuals. However, in a deregulated fee environment these benefits now risk being outweighed by the mounting costs of education for those who wish to improve their qualifications. This paper revisits a paper by Smith and Frankland in 2000, regarding the 'marketisation' of postgraduate coursework degrees in Australia and addresses the likely implications of recent proposals for a cap on the combined cumulative fee debt for current and prospective postgraduate coursework students. It finds that many of the predictions made by Smith and Frankland in 2000 have been borne out and that the prospect of limits on cumulative debt from multiple degree programs has the potential to have an impact on increasing numbers of graduates with fee debts well in excess of $100,000. [To view "Marketisation and the New Quality Agenda: Postgraduate Coursework at the Crossroads," see EJ623399.]

ABSTRACT Adaptive antibiotic resistance is a transient metabolic adaptation of bacteria limiting their sensitivity to low, progressively increased, concentrations of antibiotics. Unlike innate and acquired resistance, adaptive resistance is dependent on the presence of antibiotics, and it disappears when the triggering factor is removed. Low concentrations of antibiotics are largely diffused in natural environments, in the food industry or in certain body compartments of humans when used therapeutically, or in animals when used for growth promotion. However, molecular mechanisms underlying this phenomenon are still poorly characterized. Here, we present experiments suggesting that epigenetic modifications, triggered by low concentrations of ampicillin, gentamicin, and ciprofloxacin, may modulate the sensitivity of bacteria to antibiotics. The epigenetic modifications we observed were paralleled by modifications of the expression pattern of many genes, including some of those that have been found mutated in strains with permanent antibiotic resistance. As the use of low concentrations of antibiotics is spreading in different contexts, our findings may suggest new targets and strategies to avoid adaptive antibiotic resistance. This might be very important as, in the long run, this transient adaptation may increase the chance, allowing the survival and the flourishing of bacteria populations, of the onset of mutations leading to stable resistance. IMPORTANCE In this study, we characterized the modifications of epigenetic marks and of the whole transcriptome in the adaptive response of Escherichia coli cells to low concentrations of ampicillin, gentamicin, and ciprofloxacin. As the transient adaptation does increase the chance of permanent resistance, possibly allowing the survival and flourishing of bacteria populations where casual mutations providing resistance may give an immediate advantage, the importance of this study is not only in the identification of possible molecular mechanisms underlying adaptive resistance to antibiotics, but also in suggesting new strategies to avoid adaptation.

Telomeres are structures at the ends of eukaryotic chromosomes that help maintain genomic stability. During aging, telomere length gradually shortens, producing short telomeres, which are markers of premature cellular senescence. This may contribute to age-related diseases, including Alzheimer’s disease (AD), and based on this, several studies have hypothesized that telomere shortening may characterize AD. Current research, however, has been inconclusive regarding the direction of the association between leukocyte telomere length (LTL) and disease risk. We assessed the association between LTL and AD in a retrospective case–control study of a sample of 255 unrelated patients with late-onset AD (LOAD), including 120 sporadic cases and 135 with positive family history for LOAD, and a group of 279 cognitively healthy unrelated controls, who were all from Calabria, a southern Italian region. Following regression analysis, telomeres were found significantly shorter in LOAD cases than in controls (48% and 41% decrease for sporadic and familial cases, respectively; p < 0.001 for both). Interestingly, LTL was associated with disease risk independently of the presence of conventional risk factors (e.g., age, sex, MMSE scores, and the presence of the APOE-ε4 allele). Altogether, our findings lend support to the notion that LTL shortening may be an indicator of the pathogenesis of LOAD.

Background: Cardiovascular diseases (CVDs) are leading global causes of mortality. Unhealthy diets have been linked to an increased risk of CVD, while plant-based diets have shown potential protective effects. This umbrella review summarizes the evidence on the association between vegetarian diets and cardiovascular and cerebrovascular diseases. Methods: PubMed, Scopus, Embase, CINAHL, Cochrane, and Web of Science were consulted. Meta-analyses grouped by author and outcome were performed. The heterogeneity was evaluated using I2 statistics. Results: There was a 41.2% risk reduction for cerebrovascular disease. CVD incidence had a 29% reduced risk. CVD mortality had a 13.8% risk reduction, while IHD incidence had a 24.1% reduction, but with high heterogeneity. IHD mortality showed a significant 32.1% risk reduction. Ischemic stroke had a significant 32.9% risk reduction across six studies. Stroke incidence showed a significant 39.1% risk reduction in a single study. There was a non-significant 11.6% risk reduction for stroke mortality with moderate heterogeneity. Conclusion: Healthier diets are associated with reduced risks of cerebrovascular disease, CVD incidence, IHD mortality, and ischemic stroke. However, evidence quality and consistency vary, emphasizing the need for more research. Policymakers and healthcare professionals should prioritize promoting healthy diets for CVD prevention.

The world of telecommunications, from some years, is revitalizing an high interest to Deep Space Communication (DSC) and Delay Tolerant Network (DTN) architecture as enabling technologies to offer internet services for aerospace vehicles or orbital stations. The communications between the planets in the solar system is well known to present a series of problems that need to be faced. The fundamental challenge with InterPlanetary Communication (IPC) is the intermittent Line of Sight (LoS) caused by planets movement and the significant propagation time. A possible way to face with it is the use of a DTN approach where routers use a store-and-forward transmission in a hop-by-hop message exchange mechanism. Thanks to this approach, it is possible to face many issues related to the transport layer. The main contribution of this work concerns the proposal of a bundle management layer able to assign at the receiver the appropriate bundle rate on the basis of concurrent bundle transmissions, the output link capacity and buffer resources. The proposed strategy can be integrated with a routing algorithm for InterPlanetary Networks (IPNs) and DTN networks. In our case we consider the Earliest Arrival Optimal Delivery Ratio (EAODR) routing that applies a modified temporal graph to select the IPN nodes. Performance evaluation have been led out to show the benefits of our proposal on the single links and also on the routing scheme in terms of bundle delivery ratio and average bundle delivery time.

The mass storage of hydrogen is a challenge considering large industrial applications and continuous distribution, e.g., for domestic use as a future energy carrier that respects the environment. For a long time, molecular hydrogen was stored and distributed, either as a gas (pressurized up to 75 MPa) or as a cryogenic liquid (20.4 K). Furthermore, the atomic storage of hydrogen in the solid-state form via metallic or covalent compounds is still the subject of intense research and limited to a small scale for some practical developments. In addition, other type H chemical storage routes are being tested, such as ammonia and LOHC (Liquid Organic Hydrogen Carrier), etc. In any case, the main constraint remains security. However, Hydrogen Solid State Storage (HSSS) using MgH2 bodies has been shown to be feasible in terms of process and safety. Furthermore, its intrinsic volumetric densification was proven to be much better performing with 106:70:45 kgH2/m3 for solid (RT):LH (20.4 K):gas (75 MPa), respectively. Very early on, fairly reactive MgH2-based pellets were produced (for max. ~27 tons/year) at McPhy Energy using a series of unique and self-built installations. Thus, the design of large instrumented reservoirs was undertaken thanks to fundamental research first carried out at the CNRS. So, prototypes of storage units from 100 to ~5500 kWh have been produced. However, McPhy took other routes a few years ago (smelting and refueling stations) because the HSSS market was not merging at that time. Today, a new operator, Jomi–Leman, therefore, decided to try the challenge again focusing on applications with on-site production and mass HSSS.

Different nutritional regimens have been reported to exert beneficial effects on obesity through the regulation of the composition and function of gut microbiota. In this context, we conducted in obese subjects two dietary interventions consisting of a low-calorie and two-phase (ketogenic plus low-calorie) diet for 8 weeks. Anthropometric and clinical parameters were evaluated at baseline and following the two diets, and gut microbiota composition was assessed by 16S rRNA gene sequencing. A significant reduction was observed for abdominal circumference and insulin levels in the subjects following the two-phase diet. Significant differences in gut microbial composition were observed after treatment compared to the baseline. Both diets induced taxonomic shifts including a decrease in Proteobacteria, which are recognized as dysbiosis markers and enrichment of Verrucomicrobiaceae, which has recently emerged as an effective probiotic. An increase in Bacteroidetes, constituting the so-called good bacteria, was observable only in the two-phase diet. These findings provide evidence that a targeted nutritional regimen and an appropriate use of probiotics can modulate gut microbiota to reach a favorable composition and achieve the balance often compromised by different pathologies and conditions, such as obesity.

Introduction: During the coronavirus disease 2019 (COVID-19) pandemic, hospitals rapidly ran out of intensive care beds. Because minimally invasive surgery and general anaesthesia are both aerosol-generating procedures, their use has become controversial. We report a case series of awake undelayable colorectal surgeries which, innovatively, took advantage of intraoperative pain distraction. Moreover, we describe our frugal solution to social distancing in psychological support of inpatients.Methods: Between October 2020 and February 2021, five patients underwent acute-care colorectal surgery under locoregional anaesthesia in our department. A 3D mobile theatre (3DMT) was used during the operation to distract the patients from pain. Vital signs, pain intensity, ergonomic comfort/discomfort, sense of presence and distress were intraoperatively monitored. A postoperative “cuddle delivery” service was instituted: video messages from relatives and close friends were delivered daily to the patient through the 3DMT. Emotional effects were investigated through clinical interviews conducted by a psychologist at our hospital.Results: Both intraoperative and postoperative pain were always well controlled. Conversion to general anaesthesia and postoperative intensive support/monitoring were never necessary. The “cuddle delivery” initiative helped patients fill the emotional gap created by the strict containment measures implemented inside the hospital, distracting them from emotional anxiety and physical pain.Conclusions: During the next phase of the COVID-19 pandemic and even after the COVID-19 era, awake laparotomy under locoregional anaesthesia may be a crucial option for delivering acute-care surgery to selected patients when intensive care beds are unavailable and postponing surgery is unacceptable. We also introduce a new modality for the provision of emotional support during postoperative inpatient care as a countermeasure to the restrictions imposed by social distancing measures.

Virtual private network (VPN) represents an HW/SW infrastructure that implements private and confidential communication channels that usually travel through the Internet. VPN is currently one of the most reliable technologies to achieve this goal, also because being a consolidated technology, it is possible to apply appropriate patches to remedy any security holes. In this paper we analyze the performances of open source firmware OpenWrt 21.x compared with a server-side operating system (Debian 11 x64) and Mikrotik 7.x, also virtualized, and different types of clients (Windows 10/11, iOS 15, Android 11, OpenWrt 21.x, Debian 11 x64 and Mikrotik 7.x), observing the performance of the network according to the current implementation of the various protocols and algorithms of VPN tunnel examined on what are the most recent HW and SW for deployment in outdoor locations with poor network connectivity. Specifically, operating systems provide different performance metric values for various combinations of configuration variables. The first pursued goal is to find the algorithms to guarantee a data transmission/encryption ratio as efficiently as possible. The second goal is to research the algorithms capable of guaranteeing the widest spectrum of compatibility with the current infrastructures that support VPN technology, to obtain a connection system secure for geographically scattered IoT networks spread over difficult-to-manage areas such as suburban or rural environments. The third goal is to be able to use open firmware on constrained routers that provide compatibility with different VPN protocols.

This paper presents an automatic recognition system for classifying stones belonging to different Calabrian quarries (Southern Italy). The tool for stone recognition has been developed in the SILPI project (acronym of “Sistema per l’Identificazione di Lapidei Per Immagini”), financed by POR Calabria FESR-FSE 2014-2020. Our study is based on the Convolutional Neural Network (CNNs) that is used in literature for many different tasks such as speech recognition, neural language processing, bioinformatics, image classification and much more. In particular, we propose a two-stage hybrid approach based on the use of a model of Deep Learning (DL), in our case the CNN, in the first stage and a model of Machine Learning (ML) in the second one. In this work, we discuss a possible solution to stones classification which uses a CNN for the feature extraction phase and the Softmax or Multinomial Logistic Regression (MLR), Support Vector Machine (SVM), k-Nearest Neighbors (kNN), Random Forest (RF) and Gaussian Naive Bayes (GNB) ML techniques in order to perform the classification phase basing our study on the approach called Transfer Learning (TL). We show the image acquisition process in order to collect adequate information for creating an opportune database of the stone typologies present in the Calabrian quarries, also performing the identification of quarries in the considered region. Finally, we show a comparison of different DL and ML combinations in our Two-Stage Hybrid Model solution.

Extreme longevity is the paradigm of healthy aging as individuals who reached the extreme decades of human life avoided or largely postponed all major age-related diseases. In this study, we sequenced at high coverage (90X) the whole genome of 81 semi-supercentenarians and supercentenarians [105+/110+] (mean age: 106.6 ± 1.6) and of 36 healthy unrelated geographically matched controls (mean age 68.0 ± 5.9) recruited in Italy. The results showed that 105+/110+ are characterized by a peculiar genetic background associated with efficient DNA repair mechanisms, as evidenced by both germline data (common and rare variants) and somatic mutations patterns (lower mutation load if compared to younger healthy controls). Results were replicated in a second independent cohort of 333 Italian centenarians and 358 geographically matched controls. The genetics of 105+/110+ identified DNA repair and clonal haematopoiesis as crucial players for healthy aging and for the protection from cardiovascular events.

Wireless Sensor Networks (WSNs) are networks of small devices with limited resources which are able to collect different information for a variety of purposes. Energy and security play a key role in these networks and MAC aspects are fundamental in their management. The classical security approaches are not suitable in WSNs given the limited resources of the nodes, which subsequently require lightweight cryptography mechanisms in order to achieve high security levels. In this paper, a security analysis is provided comparing BMAC and LMAC protocols, in order to determine, using AES, RSA, and elliptic curve techniques, the protocol with the best trade-off in terms of received packets and energy consumption.

Large-scale coordinated efforts have been dedicated to understanding the global health and economic implications of the COVID-19 pandemic. Yet, the rapid spread of discrimination and xenophobia against specific populations has largely been neglected. Understanding public attitudes toward migration is essential to counter discrimination against immigrants and promote social cohesion. Traditional data sources to monitor public opinion are often limited, notably due to slow collection and release activities. New forms of data, particularly from social media, can help overcome these limitations. While some bias exists, social media data are produced at an unprecedented temporal frequency, geographical granularity, are collected globally and accessible in real-time. Drawing on a data set of 30.39 million tweets and natural language processing, this article aims to measure shifts in public sentiment opinion about migration during early stages of the COVID-19 pandemic in Germany, Italy, Spain, the United Kingdom, and the United States. Results show an increase of migration-related Tweets along with COVID-19 cases during national lockdowns in all five countries. Yet, we found no evidence of a significant increase in anti-immigration sentiment, as rises in the volume of negative messages are offset by comparable increases in positive messages. Additionally, we presented evidence of growing social polarization concerning migration, showing high concentrations of strongly positive and strongly negative sentiments.

Si306, a pyrazolo[3,4-d]pyrimidine derivative recently identified as promising anticancer agent, has shown favorable in vitro and in vivo activity profile against neuroblastoma (NB) models by acting as a competitive inhibitor of c-Src tyrosine kinase. Nevertheless, Si306 antitumor activity is associated with sub-optimal aqueous solubility, which might hinder its further development. Drug delivery systems were here developed with the aim to overcome this limitation, obtaining suitable formulations for more efficacious in vivo use. Si306 was encapsulated in pegylated stealth liposomes, undecorated or decorated with a monoclonal antibody able to specifically recognize and bind to the disialoganglioside GD2 expressed by NB cells (LP[Si306] and GD2-LP[Si306], respectively). Both liposomes possessed excellent morphological and physio-chemical properties, maintained over a period of two weeks. Compared to LP[Si306], GD2-LP[Si306] showed in vitro specific cellular targeting and increased cytotoxic activity against NB cell lines. After intravenous injection in healthy mice, pharmacokinetic profiles showed increased plasma exposure of Si306 when delivered by both liposomal formulations, compared to that obtained when Si306 was administered as free form. In vivo tumor homing and cytotoxic effectiveness of both liposomal formulations were finally tested in an orthotopic animal model of NB. Si306 tumor uptake resulted significantly higher when encapsulated in GD2-LP, compared to Si306, either free or encapsulated into untargeted LP. This, in turn, led to a significant increase in survival of mice treated with GD2-LP[Si306]. These results demonstrate a promising antitumor efficacy of Si306 encapsulated into GD2-targeted liposomes, supporting further therapeutic developments in pre-clinical trials and in the clinic for NB.

Nutrition plastically modulates the epigenetic landscape in various tissues of an organism during life via epigenetic changes. In the present study, to clarify whether this modulation involves RNA methylation, we evaluated global RNA methylation profiles and the expression of writer, reader, and eraser genes, encoding for enzymes involved in the RNA methylation. The study was carried out in the heart, liver, and kidney samples from rats of different ages in response to a low-calorie diet. We found that, although each tissue showed peculiar RNA methylation levels, a general increase in these levels was observed throughout the lifespan as well as in response to the six-month diet. Similarly, a prominent remodeling of the expression of writer, reader, and eraser genes emerged. Our data provide a comprehensive overview of the role exerted by diet on the tissue-specific epigenetic plasticity of RNA according to aging in rats, providing the first evidence that methylation of RNA, similarly to DNA methylation, can represent an effective biomarker of aging. What is more, the fact that it is regulated by nutrition provides the basis for the development of targeted approaches capable of guaranteeing the maintenance of a state of good health.

Background: Various studies, mostly with animals, have provided evidence of adverse impacts of fluoride (F-) on bone density, collagen and microstructure, yet its effects on overall bone quality (strength) has not been clearly or extensively characterized in human populations. Objective: In this observational study, we assessed variation in an integrated measures of bone quality in a population exposed to wide-ranging F- levels (0.3 to 15.5 mg/L) in drinking water, using a novel application of non-ionizing ultrasonic method. Method: We collected 871 speed of sound (SOS) measurements from 341 subjects residing in 25 communities, aged 10–70 years (188 males and 153 females). All subjects received scans of the cortical radius and tibia, and adults over the age of 19 received an additional scan of the phalanx. Associations between F- in drinking water and 24-h urine samples, and SOS as a measure of bone quality, were evaluated in bivariate and multivariable regressions adjusting for age, sex, BMI, smoking, and toothpaste use. Results: We found negative associations between F- exposure and bone quality at all three bones. Adult tibial SOS showed the strongest inverse association with F- exposure, which accounted for 20% of the variance in SOS measures (r = 0.45; n = 199; p