Cell cycle-dependent resolution of DNA double-strand breaks

DNA double strand breaks (DSBs) elicit prompt activation of DNA damage response (DDR), which arrests cell-cycle either in G1/S or G2/M in order to avoid entering S and M phase with damaged DNAs. Since mammalian tissues contain both proliferating and quiescent cells, there might be fundamental difference in DDR between proliferating and quiescent cells (or G0-arrested). To investigate these differences, we studied recruitment of DSB repair factors and resolution of DNA lesions induced at site-specific DSBs in asynchronously proliferating, G0-, or G1-arrested cells. Strikingly, DSBs occurring in G0 quiescent cells are not repaired and maintain a sustained activation of the p53-pathway. Conversely, re-entry into cell cycle of damaged G0-arrested cells, occurs with a delayed clearance of DNA repair factors initially recruited to DSBs, indicating an inefficient repair when compared to DSBs induced in asynchronously proliferating or G1-synchronized cells. Moreover, we found that initial recognition of DSBs and assembly of DSB factors is largely similar in asynchronously proliferating, G0-, or G1-synchronized cells. Our study thereby demonstrates that repair and resolution of DSBs is strongly dependent on the cell-cycle state

From BEXUS to HEMERA: The application of lessons learned on the development and manufacturing of stratospheric payloads at S5Lab

In the last years the S5Lab (Sapienza Space Systems and Space Surveillance Laboratory) from Sapienza University of Rome has given to the students the opportunity to gather knowledge on stratospheric payloads by supporting the design and development of two experiments selected for the participation in the REXUS/BEXUS educational Programme, managed by three european space institutions. The insights and lessons learned gathered during the participations in the REXUS/BEXUS educational programme gave the possibility to the student to take part in the development of a third experiment in the frame of the professional research programme HEMERA and complete it successfully. STRATONAV (STRATOspheric NAVigation experiment) was a stratospheric experiment based on Software Defined Radios (SDRs) technology whose aim was the testing of the VOR (VHF Omnidirectional Range) navigation system, evaluating its performance above the standard service volume, which was launched on BEXUS 22 in October 2016. TARDIS (Tracking and Attitude Radio-based Determination In Stratosphere) was developed as a follow up of STRATONAV between 2018 and 2019. Similarly to its predecessor TARDIS was a stratospheric experiment aimed at exploiting the VOR signal, with the aid of SDRs, to perform in-flight attitude and position determination, and was launched on BEXUS 28 in October 2019. After the launch of TARDIS, a team composed both by former STRATONAV and TARDIS students was formed for the development of a third stratospheric experiment going by the name of STRAINS (Stratospheric Tracking Innovative Systems), conceived by Sapienza University of Rome and ALTEC and supported by ASI. STRAINS main objective was the proof of concept of the possibility of achieving the Time Difference of Arrival (TDOA) and the Frequency Difference of Arrival (FDOA) for navigation purposes with the aid of SDRs. The experiment was developed between 2020 and 2021 exploiting the lessons learned from the former team members of the two BEXUS campaigns and was launched on board of the Hemera H2020 stratospheric balloon in September 2021 from Esrange Space Center, Kiruna, Sweden. After a brief description of the stratospheric payloads design and manufacturing, the paper will present the major lessons learned from the previous stratospheric experiments, STRATONAV and TARDIS, and their application to the development and manufacturing of the latest launched stratospheric experiment STRAINS, as well as their educational return to the students involved in the projects

Genome-wide mapping of 8-oxo-7,8-dihydro-2'-deoxyguanosine reveals accumulation of oxidatively-generated damage at DNA replication origins within transcribed long genes of mammalian cells

8-Oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG) is one of the major DNA modifications and a potent pre-mutagenic lesion prone to mispair with 2- deoxyadenosine (dA). Several thousand residues of 8-oxodG are constitutively generated in the genome of mammalian cells, but their genomic distribution has not yet been fully characterized. Here, by using OxiDIP-Seq, a highly sensitive methodology that uses immuno-precipitation with efficient anti– 8-oxodG antibodies combined with high-throughput sequencing, we report the genome-wide distribution of 8-oxodG in human non-tumorigenic epithelial breast cells (MCF10A), and mouse embryonic fibroblasts (MEFs). OxiDIP-Seq revealed sites of 8- oxodG accumulation overlapping with H2AX ChIPSeq signals within the gene body of transcribed long genes, particularly at the DNA replication origins contained therein. We propose that the presence of persistent single-stranded DNA, as a consequence of transcription-replication clashes at these sites, determines local vulnerability to DNA oxidation and/or its slow repair. This oxidatively-generated damage, likely in combination with other kinds of lesion, might contribute to the formation of DNA double strand breaks and activation of DNA damage response

The interplay among psychopathology, personal resources, context-related factors and real-life functioning in schizophrenia: stability in relationships after 4 years and differences in network structure between recovered and non-recovered patients

Improving real-life functioning is the main goal of the most advanced integrated treatment programs in people with schizophrenia. The Italian Network for Research on Psychoses previously explored, by using network analysis, the interplay among illness-related variables, personal resources, context-related factors and real-life functioning in a large sample of patients with schizophrenia. The same research network has now completed a 4-year follow-up of the original sample. In the present study, we used network analysis to test whether the pattern of relationships among all variables investigated at baseline was similar at follow-up. In addition, we compared the network structure of patients who were classified as recovered at follow-up versus those who did not recover. Six hundred eighteen subjects recruited at baseline could be assessed in the follow-up study. The network structure did not change significantly from baseline to follow-up, and the overall strength of the connections among variables increased slightly, but not significantly. Functional capacity and everyday life skills had a high betweenness and closeness in the network at follow-up, as they had at baseline, while psychopathological variables remained more peripheral. The network structure and connectivity of non-recovered patients were similar to those observed in the whole sample, but very different from those in recovered subjects, in which we found few connections only. These data strongly suggest that tightly coupled symptoms/dysfunctions tend to maintain each other's activation, contributing to poor outcome in schizophrenia. Early and integrated treatment plans, targeting variables with high centrality, might prevent the emergence of self-reinforcing networks of symptoms and dysfunctions in people with schizophrenia

The interplay among psychopathology, personal resources, context-related factors and real-life functioning in schizophrenia: stability in relationships after 4 years and differences in network structure between recovered and non-recovered patients

Improving real-life functioning is the main goal of the most advanced integrated treatment programs in people with schizophrenia. The Italian Network for Research on Psychoses previously explored, by using network analysis, the interplay among illness-related variables, personal resources, context-related factors and real-life functioning in a large sample of patients with schizophrenia. The same research network has now completed a 4-year follow-up of the original sample. In the present study, we used network analysis to test whether the pattern of relationships among all variables investigated at baseline was similar at follow-up. In addition, we compared the network structure of patients who were classified as recovered at follow-up versus those who did not recover. Six hundred eighteen subjects recruited at baseline could be assessed in the follow-up study. The network structure did not change significantly from baseline to follow-up, and the overall strength of the connections among variables increased slightly, but not significantly. Functional capacity and everyday life skills had a high betweenness and closeness in the network at follow-up, as they had at baseline, while psychopathological variables remained more peripheral. The network structure and connectivity of non-recovered patients were similar to those observed in the whole sample, but very different from those in recovered subjects, in which we found few connections only. These data strongly suggest that tightly coupled symptoms/dysfunctions tend to maintain each other's activation, contributing to poor outcome in schizophrenia. Early and integrated treatment plans, targeting variables with high centrality, might prevent the emergence of self-reinforcing networks of symptoms and dysfunctions in people with schizophrenia

Accuracy of self-assessment of real-life functioning in schizophrenia

A consensus has not yet been reached regarding the accuracy of people with schizophrenia in self-reporting their real-life functioning. In a large (n=618) cohort of stable, community-dwelling schizophrenia patients we sought to: (1) examine the concordance of patients' reports of their real-life functioning with the reports of their key caregiver; (2) identify which patient characteristics are associated to the differences between patients and informants. Patient-caregiver concordance of the ratings in three Specific Level of Functioning Scale (SLOF) domains (interpersonal relationships, everyday life skills, work skills) was evaluated with matched-pair t tests, the Lin's concordance correlation, Somers' D, and Bland-Altman plots with limits of agreement (LOA). Predictors of the patient-caregiver differences in SLOF ratings were assessed with a linear regression with multivariable fractional polynomials. Patients' self-evaluation of functioning was higher than caregivers' in all the evaluated domains of the SLOF and 17.6% of the patients exceeded the LOA, thus providing a self-evaluation discordant from their key caregivers. The strongest predictors of patient-caregiver discrepancies were caregivers' ratings in each SLOF domain. In clinically stable outpatients with a moderate degree of functional impairment, self-evaluation with the SLOF scale can become a useful, informative and reliable clinical tool to design a tailored rehabilitation program

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

Influenza della destagionalizzazione nella bufala sulla quota di avvicendamento annuo e sull'incidenza dei parti nel periodo gennaio-giugno

Replacement rates between wmpty buffaloes in which sexual promiscuity was interrupted from November to March in order to shift the conception period to spring and buffaloes which conceived before November were compared. The calving data of 7519 buffaloes (5 farms) were elaborate

Tecnologie utilizzate per la rilevazione dei calori e inseminazione strumentale nella specie bufalina.

The use of artificial insemination as a primary reproduction technique obviously makes it necessary to identify the animals on heat. The use of synchronization makes artificial insemination easier in as much that insemination is carried out at fixed times. However it cannot be used on all the animals throughout the year. In the buffalo farm in Italy the identification of females on heat is not usually part of the official duties of the herdsmen. Since artificial insemination is not routinely used, readings taken are used only to add to the anamnesis of the individual animal and to give extra data to the veterinary expert or, in some cases, to ascertain the paternity of a calf. It is difficult to persuade the staff to perform a task that is different from the duties normally required. Moreover it is difficult to recognise the animals by simply looking at them. Their coats are a uniform colour. The identification tags applied to the buffalo are often impossible to read on account of encrusted mud. It has already been noted that female buffalo do not ostensibly manifest reciprocal covering postures. One means of identifying animals on heat is to use a vasectomized bull. This has a dual function. Firstly to identify the animals on heat and secondly to improve the reproductive efficiency of the herd thanks to the “bull effect” (51) on female buffaloes which has already been described. In the last few years our Research Unit has been investigating the possibility of adopting pedometers for use on farms. The need to develop new technologies to identify animals on heat stems from the dairy cattle industry where the problem of synchronizing artificial insemination and the oestrous cycle is all the more pressing and where the success in the identification of fertile periods is reported to be still around 50%. The first observation that the walking activity of female mammals increases at the onset of the oestrous phase in the sexual cycle was eighty years ago. Later studies showed that the onset of the oestrous phase differed from that of all the other phases in the cycle. Pedometers are instruments which measure the number of steps taken in a given time. The data can then be processed in relation to the motor activity of the animal in the preceding days and expressed as a percentage of a sample period (8 – 10 days). A computer is able to trigger a series of signals when motor activity exceeds the average recorded for the previous days by a certain percentage, indicating that the animal is now on heat. Pedometers were installed experimentally on a buffalo farm of 250 adults. They proved to be a useful accessory in artificial insemination in cases of spontaneous heat and provided useful information concerning their potential for further use The average length of the heat period registered by the pedometers was about 17 hours with small variations according to the month of the year. Covering by the bull, when present, occurred, on average, about eight hours after the first signal from the pedometer. Ovulation occurred on average 24.4 hours after the first signal of heat from the pedometer. However, ovulation also took place earlier in buffaloes for which there had been only one signal from the pedometer than for those which had two or more signals. 9.8 % of the cases of the onset of heat signalled by the pedometer and confirmed by gynaecological examination were accompanied by high readings of progesterone (> 1.5 ng/ml in the blood). Almost 11 % of these signals came from subjects that were already pregnant; of these 17.6 % were confirmed to be on heat by clinical examination Sensitivity in the signalling of the onset of heat ranged from 85-98 % and accuracy was 75 %. These readings tally with those recorded for dairy cows. The system examined showed an increase in sensitivity of over 90 % when considered in association with the signals provided by the vasectomized bull and herdsmen