Dynamical model of DNA-protein interaction: effect of protein charge distribution and mechanical properties

The mechanical model based on beads and springs, which we recently proposed to study non-specific DNA-protein interactions [J. Chem. Phys. 130, 015103 (2009)], was improved by describing proteins as sets of interconnected beads instead of single beads. In this paper, we first compare the results obtained with the updated model with those of the original one and then use it to investigate several aspects of the dynamics of DNA sampling, which could not be accounted for by the original model. These aspects include the effect on the speed of DNA sampling of the regularity and/or randomness of the protein charge distribution, the charge and location of the search site, and the shape and deformability of the protein. We also discuss the efficiency of facilitated diffusion, that is, the extent to which the combination of 1D sliding along the DNA and 3D diffusion in the cell can lead to faster sampling than pure 3D diffusion of the protein.Comment: accepted in JC

Free energy landscape and characteristic forces for the initiation of DNA unzipping

DNA unzipping, the separation of its double helix into single strands, is crucial in modulating a host of genetic processes. Although the large-scale separation of double-stranded DNA has been studied with a variety of theoretical and experimental techniques, the minute details of the very first steps of unzipping are still unclear. Here, we use atomistic molecular dynamics (MD) simulations, coarse-grained simulations and a statistical-mechanical model to study the initiation of DNA unzipping by an external force. The calculation of the potential of mean force profiles for the initial separation of the first few terminal base pairs in a DNA oligomer reveal that forces ranging between 130 and 230 pN are needed to disrupt the first base pair, values of an order of magnitude larger than those needed to disrupt base pairs in partially unzipped DNA. The force peak has an "echo," of approximately 50 pN, at the distance that unzips the second base pair. We show that the high peak needed to initiate unzipping derives from a free energy basin that is distinct from the basins of subsequent base pairs because of entropic contributions and we highlight the microscopic origin of the peak. Our results suggest a new window of exploration for single molecule experiments.Comment: 25 pages, 6 figures , Accepted for publication in Biophysical Journa

Digital Commons and Management towards Sustainability, Equity and Resilience

This Research in Progress paper is a literature review on management activities and processes that take place within the digital commons, through the lenses of three pillars: sustainability, equity and resilience. The aim is to examine previous studies, in order to be able to answer the following question: how can the environmental sustainability, equity and resilience of digital commons be improved? Initial research shows few results on this topic. But, more than answers, this literature review highlights three avenues of research

Main Features of Prevalence and Severity of Major Depressive Episode in Romania

The objectives of the current article are to present some nationally representative estimates of lifetime, 12-months prevalence of MDE the age of onset, years in episode, the effects of MDE on role impairment. The lifetime prevalence of MDE was 3.3% for “all ages”, with higher values for females than for males (4.1% versus 2.5%) and the prevalence estimates of CIDI/DSM-IV 12-months Major Depressive Episode (MDE) was 1.8% (2.2% for females and 1.4% for males).  Approximately half of those with lifetime prevalence MDE presented 12-months MDE too (53.8%).  Within the age groups “18-34”, “all ages” and “50-64”, the females have the mean onset of MDE earlier than males (a slight difference for the first two situations, a difference of about 8 years for the latter). Within the age groups “35-49” of “65 years and over”, the males have the onset of MDE earlier than the females with 3-4 years. Regarding the mean number of years in episode, for all subjects was found a value of 5.7 years. Symptom severity assessed with the Quick Inventory of Depressive Symptomatology Self Report (QIDS-SR), revealed that almost two thirds of cases with MDE were “severe” or “very severe” from clinical point of view.  Number of weeks depressed in the 365 days before the interview, expressed as mean was 30.8 for those with “severe” symptoms/domain. In the past 30 days, the highest WHODAS score was for out of role domain (36.2), then for mobility (14.6).  Regarding the number of days out of role in the last year due to depression, this was 82.1 for the age group “50-64” and 63.5 for those of “65 years old and over”.  Major Depression Episode is a seriously impairment condition. The severe consequences of the depression on functioning in labour and social areas call attention to the need for early diagnostic, proper treatment and intervention. Key words: major depressive episode, lifetime prevalence, 12-mo prevalence, Sheehan score, disability assessment schedul

Description of non-specific DNA-protein interaction and facilitated diffusion with a dynamical model

We propose a dynamical model for non-specific DNA-protein interaction, which is based on the 'bead-spring' model previously developed by other groups, and investigate its properties using Brownian Dynamics simulations. We show that the model successfully reproduces some of the observed properties of real systems and predictions of kinetic models. For example, sampling of the DNA sequence by the protein proceeds via a succession of 3d motion in the solvent, 1d sliding along the sequence, short hops between neighboring sites, and intersegmental transfers. Moreover, facilitated diffusion takes place in a certain range of values of the protein effective charge, that is, the combination of 1d sliding and 3d motion leads to faster DNA sampling than pure 3d motion. At last, the number of base pairs visited during a sliding event is comparable to the values deduced from single-molecule experiments. We also point out and discuss some discrepancies between the predictions of this model and some recent experimental results as well as some hypotheses and predictions of kinetic models

Different approaches in treatment of infected non-unions

Introduction: We present the case of a 60 years old patient involved in a car accident with trochanteric fracture and open type I comminutive 1/3 proximal right tibial fracture. For the treatment of trochanteric fracture DHS (dynamic hip screw) was used and for the tibial fracture we opted for plate and screws. Due to the absence of complete bone consolidation, the plate was removed and another surgery using intramedullar nail and plate for the tibial tuberosity was performed. Unfortunately patient did not follow the hygienic conditions as a consequence he contacted an infection which led to septic non-union. To treat this new situation the device was removed and an Ilizarov frame was used. This technique allowed radical resection of the infected bone. For lengthening procedures, a percutaneous “corticotomy” was used in which the accessible cortices of tibia were cut, avoiding as much as possible penetration of medullary canal. The wires were tensioned up to 130 kg to provide adequate stiffness for bone segment stability and correction of axial, translational and rotational deformities. Even with this lengthy period of fixing wear (1.5 months for each cm of lengthening), the Ilizarov procedure was very helpful for this patient who needed extensive resection of bone and reconstruction to achieve stability. Methods: The treatment option was DHS for trochanteric fracture and plate and screws for tibial fracture. Patient developed non-union at the level of tibial metaphysic as a consequence the plate was removed. After the procedure we opted for intramedullary nail for tibial fracture and plate for tibial tuberosity. However the patient did not fallow the postoperative indications as a result he developed septic non-union. Due to the infected non-union we opted for the Ilizarov technique. Results: This technique was very effective in treatment of septic non-union, which needed large excision of bone. The patient recovered completely and regained the mobility of his leg. Conclusion: The Ilizarov procedure benefits patients who need extensive resection of bone and reconstruction to achieve stability. Disadvantages include the time required to achieve a solid union (six weeks for each centimeter of lengthening) and the high incidence of associated complications (minor pin track infection, residual equinus contracture, a nerve palsy or unexpected sequel that can compromise the final results)

Active surveillance of adverse events after immunization (AEFI) from the Local Health Unit of Ferrara, Italy

IntroductionVaccine vigilance implies the collection, evaluation, analysis and communication of adverse events following immunization (AEFI) and is a useful tool for vaccine monitoring allowing, even after approval and marketing, to check its safety/tolerability. The multiregional project "Active surveillance of adverse vaccine reactions", joined by the AUSL of Ferrara, is aimed at making parents of children, who have undergone at least one vaccination provided by the regional vaccination calendar in the first 24 months of life, aware of the reporting of any AEFI via mobile phone-SMS.MethodsAn analysis of the project data, collected in the period March 2018 - May 2019, was carried out, to evaluate the effectiveness of the reporting tool and the type and frequency of AEFI. Anonymized data were analyzed by number, gender, distribution by age, type of vaccine, adverse event, severity and outcome.ResultsA total of 1494 consents and 983 SMS messages were obtained from parents.The vaccine doses carried out were 1,984 (28.3% hexavalent, 28% PCV13, 17% anti-rotavirus, 14.3% Men-B). Almost all (99.5%) AEFI were classified as "not serious".Based on the Organ System Class (SOC), most reports are related to "General Disorders and Administration Site Conditions" (52.3%), followed by "Psychiatric Disorders" (26.5%) and "Metabolic and nutrition disorders" (12.5%).ConclusionsThe reported AEFI are in line with the ones reported in the literature.Reporting via SMS is a valid vaccine surveillance tool contributing to the qualitative and quantitative improvement of the information transmitted