8-Chloro-Cyclic AMP and Protein Kinase A I-Selective Cyclic AMP Analogs Inhibit Cancer Cell Growth through Different Mechanisms

Cyclic AMP (cAMP) inhibits the proliferation of several tumor cells. We previously reported an antiproliferative effect of PKA I-selective cAMP analogs (8-PIP-cAMP and 8-HA-cAMP) on two human cancer cell lines of different origin. 8-Cl-cAMP, another cAMP analog with known antiproliferative properties, has been investigated as a potential anticancer drug. Here, we compared the antiproliferative effect of 8-Cl-cAMP and the PKA I-selective cAMP analogs in three human cancer cell lines (ARO, NPA and WRO). 8-Cl-cAMP and the PKA I-selective cAMP analogs had similarly potent antiproliferative effects on the BRAF-positive ARO and NPA cells, but not on the BRAF-negative WRO cells, in which only 8-Cl-cAMP consistently inhibited cell growth. While treatment with the PKA I-selective cAMP analogs was associated with growth arrest, 8-Cl-cAMP induced apoptosis. To further investigate the actions of 8-Cl-cAMP and the PKA I-selective cAMP analogs, we analyzed their effects on signaling pathways involved in cell proliferation and apoptosis. Interestingly, the PKA I-selective cAMP analogs, but not 8-Cl-cAMP, inhibited ERK phosphorylation, whereas 8-Cl-cAMP alone induced a progressive phosphorylation of the p38 mitogen-activated protein kinase (MAPK), via activation of AMPK by its metabolite 8-Cl-adenosine. Importantly, the pro-apoptotic effect of 8-Cl-cAMP could be largely prevented by pharmacological inhibition of the p38 MAPK. Altogether, these data suggest that 8-Cl-cAMP and the PKA I-selective cAMP analogs, though of comparable antiproliferative potency, act through different mechanisms. PKA I-selective cAMP analogs induce growth arrest in cells carrying the BRAF oncogene, whereas 8-Cl-cAMP induce apoptosis, apparently through activation of the p38 MAPK pathway

Hydrological Web Services for Operational Flood Risk Monitoring and Forecasting at Local Scale in Niger

Emerging hydrological services provide stakeholders and political authorities with useful and reliable information to support the decision-making process and develop flood risk management strategies. Most of these services adopt the paradigm of open data and standard web services, paving the way to increase distributed hydrometeorological services’ interoperability. Moreover,sharing of data, models, information, and the use of open-source software, greatly contributes to expanding the knowledge on flood risk and to increasing flood preparedness. Nevertheless, services’ interoperability and open data are not common in local systems implemented in developing countries. This paper presents the web platform and related services developed for the Local Flood Early Warning System of the Sirba River in Niger (SLAPIS) to tailor hydroclimatic information to the user’s needs, both in content and format. Building upon open-source software components and interoperable web services, we created a software framework covering data capture and storage, data flow management procedures from several data providers, real-time web publication, and service-based information dissemination. The geospatial infrastructure and web services respond to the actual and local decision-making context to improve the usability and usefulness of information derived from hydrometeorological forecasts, hydraulic models, and real-time observations. This paper presents also the results of the three years of operational campaigns for flood early warning on the Sirba River in Niger. Semiautomatic flood warnings tailored and provided to end users bridge the gap between available technology and local users’ needs for adaptation, mitigation, and flood risk management, and make progress toward the sustainable development goals

Exploring the use of modelling tools within the participatory approach to protect the water resource

Massaciuccoli lake, subsidence, numerical modelling, scenario

A Feasible Methodological Approach to Estimate the Burden of Autism Spectrum Disorder: Results from the EPI-ASD Study in the Province of Lecce (Southern Italy)

Diagnoses of Autism Spectrum Disorder (ASD) have rapidly increased globally. However, the lack of comprehensive epidemiological surveys and surveillance systems, able to provide official data at a national or European level is one of the main issues in the monitoring of this condition. The present study aimed to estimate the prevalence of ASD in children and adolescents aged 3-18 years old living in the province of Lecce (Southern Italy) through official data provided by the Local Health Authority of Lecce (ASL/LE) up to 31 October 2020, and compare it with school-based data concerning the number of students needing support for ASD. Based on data provided by the ASL/LE, in 2020 there were 509 cases of ASD among children and adolescents aged 3-18 years old, corresponding to a prevalence of 0.46%. A total of 408 (80.2%) were boys and 101 (19.8%) were girls. In relation to their age, 155 ASD cases (0.90%) were diagnosed in the 3-5 age group, while 222 (0.55%) in the 6-11 age group and 132 (0.25%) in the 12-18 age group. Prevalence of ASD assessed by school-based dataset was underestimated in the 3-5 age group, while the 6-11 and 12-18 age groups were consistent with the official data provided by the ASL/LE

Water planning and management in the Cornia river plain by means of the gis-integrated freewat platform

Coastal aquifer, Cornia valley, Tuscany, Managed Aquifer Recharge, FREEWAT platform

Risk Factors for Lung Cancer in the Province of Lecce: Results from the PROTOS Case–Control Study in Salento (Southern Italy)

In the province of Lecce (southern Italy), a higher incidence of lung cancer (LC) among men compared to regional and national data was reported. In a sub-area in the center of the province (cluster area), the incidence and mortality for LC was even higher. PROTOS is a case-control study aimed at investigating possible risk factors for LC in the province area. A total of 442 patients with LC and 1326 controls matched by sex and age living in the province of Lecce for at least 10 years were enrolled and georeferenced; they filled in a questionnaire with their personal information and exposures. For each risk factor, an Odds Ratio adjusted for all the other variables was calculated. The risk of LC increased with excessive use of alcohol in women, for those subjects with a family cancer history, for each increase in pack/year of cigarettes, for men more exposed considering the industrial district in the cluster area, and for those using pesticides in agriculture without wearing personal protective equipment. The higher incidence of adenocarcinoma in both sexes suggests that, in addition to cigarette smoking, concurrent exposures to other environmental, occupational, and life-style factors may play a role in increased cancer risk and should be more deeply explored

Array comparative genomic hybridization in retinoma and retinoblastoma tissues

In retinoblastoma, two RB1 mutations are necessary for tumor development. Recurrent genomic rearrangements may represent subsequent events required for retinoblastoma progression. Array-comparative genomic hybridization was carried out in 18 eye samples, 10 from bilateral and eight from unilateral retinoblastoma patients. Two unilateral cases also showed areas of retinoma. The most frequent imbalance in retinoblastomas was 6p gain (40%), followed by gains at 1q12-q25.3, 2p24.3-p24.2, 9q22.2, and 9q33.1 and losses at 11q24.3, 13q13.2-q22.3, and 16q12.1-q21. Bilateral cases showed a lower number of imbalances than unilateral cases (P = 0.002). Unilateral cases were divided into low-level (≤4) and high-level (÷7) chromosomal instability groups. The first group presented with younger age at diagnosis (mean 511 days) compared with the second group (mean 1606 days). In one retinoma case ophthalmoscopically diagnosed as a benign lesion no rearrangements were detected, whereas the adjacent retinoblastoma displayed seven aberrations. The other retinoma case identified by retrospective histopathological examination shared three rearrangements with the adjacent retinoblastoma. Two other gene-free rearrangements were retinoma specific. One rearrangement, dup5p, was retinoblastoma specific and included the SKP2 gene. Genomic profiling indicated that the first retinoma was a pretumoral lesion, whereas the other represents a subclone of cells bearing 'benign' rearrangements overwhelmed by another subclone presenting aberrations with higher 'oncogenic' potential. In summary, the present study shows that bilateral and unilateral retinoblastoma have different chromosomal instability that correlates with the age of tumor onset in unilateral cases. This is the first report of genomic profiling in retinoma tissue, shedding light on the different nature of lesions named 'retinoma'. (Cancer Sci 2009; 100: 465–471

Recent Changes in Hydroclimatic Patterns over Medium Niger River Basins at the Origin of the 2020 Flood in Niamey (Niger)

Niamey, the capital of Niger, is particularly prone to floods, since it is on the banks of the Niger River, which in its middle basin has two flood peaks: one in summer (the red flood) and one in winter (the black flood). In 2020, the Niger River in Niamey reached its all-time highest levels following an abundant rainy season. On the other hand, the floods in Niamey have been particularly frequent in the last decade, a symptom of a change in hydroclimatic behaviour already observed since the end of the great droughts of the 1970s and 1980s and which is identified with the name of Sahelian Paradox. This study, starting from the analysis of the 2020 flood and from the update of the rating curve of the Niamey hydrometric station, analyses the rainfall–runoff relationship on the Sahelian basins of the Medium Niger River Basin (MNRB) that are at the origin of the local flood. The comparative analysis of runoffs, annual maximum flows (AMAX) and runoff coefficients with various rainfall indices calculated on gridded datasets allowed to hydroclimatically characterise the last decade as a different period from the wet one before the drought, the dry one and the postdrought one. Compared to the last one, the current period is characterised by a sustained increase in hydrological indicators (AMAX +27%) consistent with the increase in both the accumulation of precipitation (+11%) and the number (+51%) and magnitude (+54%) of extreme events in the MNRB. Furthermore, a greater concentration of rainfall and extremes (+78%) in August contributes to reinforcing the red flood’s positive anomalies (+2.23 st.dev in 2020). The study indicates that under these conditions the frequency of extreme hydrological events in Niamey will tend to increase further also because of the concurrence of drivers such as river-bed silting and levee effects. Consequently, the study concludes with the need for a comprehensive flood-risk assessment on the Niamey city that considers both recent hydroclimatic trends and urbanisation dynamics in flood zones hence defining the most appropriate risk-reduction strategies

Using flood water in Managed Aquifer Recharge schemes as a solution for groundwater management in the Cornia valley (Italy)

The lower Cornia valley aquifer system (Tuscany, Italy) provides the only source of water for drinking, irrigation, industrial purposes and it also contributes to the water needs of the nearby Elba island. Since 60 years, intensive exploitation of groundwater resulted in consistent head lowering and water balance deficit, causing subsidence, reduction of groundwater dependent ecosystems, and salinization of freshwater resources. Rebalancing the water budget of the hydrologic system is the main objective of the LIFE REWAT project (sustainable WATer management in the lower Cornia valley through demand REduction, aquifer Recharge and river REstoration; http://www.liferewat.eu). Here, five demonstration measures (river restoration; Managed Aquifer Recharge; reuse of treated wastewater for irrigation; high irrigation efficiency scheme; leakage management in water distribution systems) are set in place for promoting water resource management, along with capacity building and participatory actions. A pilot Managed Aquifer Recharge (MAR) infiltration basin for using flood-water was designed and set in operation in Suvereto, testing the new-issued Italian regulation on artificial recharge of aquifers (DM 100/2016). The infiltration basin is located at a pre-existing topographical low near the Cornia River. The river, having intermittent flow, provides the recharge water during high flow periods, including floods, and when discharge is above the minimum ecological flow. The infiltration basin is set in a groundwater recharge area where the aquifer is constituted by gravel and sands. A preliminary project and an executive one were prepared and discussed with the relevant authorities, following one-year long monthly monitoring of surface- and ground-water. The project was supported by a groundwater flow modelling-based approach using the FREEWAT platform (www.freewat.eu). The facility consists of the following elements: i) intake work on the River Cornia; ii) the inlet structure control system, managed by quality (mass spectrometer defining surface water spectral signature) and level probes, and allowing pumping into the facility at predefined head and chemical quality thresholds; iii) a sedimentation basin; iv) the infiltration area (less than 1 ha large); v) the operational monitoring system, based on a network of piezometers where both continuous data (head, T, EC, DO) are gathered and discrete measurements/sampling performed. The cost of construction of the plant is about 300000 C well below the cost of a surface water reservoir for a similar storage. Depending on the climatic conditions, the estimated volume of diverted surface water may vary between 300000 m3/year and 2 Mm3/year. Being the facility a pilot one, diverted water discharge ranges between 20 to 50 l/s. Minimal site development and modification was required, resulting in a no-impact water-work, while providing ecosystem benefits by reconnecting and inundating former abandoned riverbeds. The effectiveness of such pilot may demonstrate the potential for Flood-MAR schemes to increase water availability in scarcity prone areas

SNPs and real-time quantitative PCR method for constitutional allelic copy number determination, the VPREB1 marker case

<p>Abstract</p> <p>Background</p> <p>22q11.2 microdeletion is responsible for the DiGeorge Syndrome, characterized by heart defects, psychiatric disorders, endocrine and immune alterations and a 1 in 4000 live birth prevalence. Real-time quantitative PCR (qPCR) approaches for allelic copy number determination have recently been investigated in 22q11.2 microdeletions detection. The qPCR method was performed for 22q11.2 microdeletions detection as a first-level screening approach in a genetically unknown series of patients with congenital heart defects. A technical issue related to the <it>VPREB1 </it>qPCR marker was pointed out.</p> <p>Methods</p> <p>A set of 100 unrelated Italian patients with congenital heart defects were tested for 22q11.2 microdeletions by a qPCR method using six different markers. Fluorescence In Situ Hybridization technique (FISH) was used for confirmation.</p> <p>Results</p> <p>qPCR identified six patients harbouring the 22q11.2 microdeletion, confirmed by FISH. The <it>VPREB1 </it>gene marker presented with a pattern consistent with hemideletion in one 3 Mb deleted patient, suggestive for a long distal deletion, and in additional five non-deleted patients. The long distal 22q11.2 deletion was not confirmed by Comparative Genomic Hybridization. Indeed, the <it>VPREB1 </it>gene marker generated false positive results in association with the rs1320 G/A SNP, a polymorphism localized within the <it>VPREB1 </it>marker reverse primer sequence. Patients heterozygous for rs1320 SNP, showed a qPCR profile consistent with the presence of a hemideletion.</p> <p>Conclusions</p> <p>Though the qPCR technique showed advantages as a screening approach in terms of cost and time, the <it>VPREB1 </it>marker case revealed that single nucleotide polymorphisms can interfere with qPCR data generating erroneous allelic copy number interpretations.</p