Specific airborne infection with characteristic symptoms – high fever, headache, persisting dry cough, loss of taste and smell and overall tiredness originates from Wuhan in China where it was ...discovered in December 2019. Due to rapid dissemination the epidemic has become a pandemic caused by coronavirus on March 11 2020. It changed the world over night and made human life different; for some it was the ultimate change. In these fluctuating times the dental medicine, especially in the developed and advancing areas, completely stopped. Responsible behaviour of dentists, aimed at stopping the spread of the virus from dental offices showed that only emergency procedures were to be performed, in cases of toothache, trauma and odontogenic infections that might put organs or systems at risk. At the same time, with the cessation of all types of treatments, there was an immediate cessation of teaching processes in all university settings for dental medicine, since the data from China strongly suggested death rates among doctors and students in close contact with infected persons. Stress and unease that have grown among people due to isolation and quarantine, the only ways of prevention of the spread of the invisible enemy will have long-lasting and visible effect on mental health of the people. Health issues in the oral cavity will most certainly occur due to the lack of regular check-ups and care. Caries and periodontal disease will appear more frequently. While we are expecting an efficient vaccine, the only way to counter the virus are epidemiological measures and responsible behaviour of every individual, in order to stop the spread of COVID-19 virus.
The main aim of this work was to find parameters for the zinc ion in human dipeptidyl peptidase III (DPP III) active site that would enable its reliable modeling. Since the parameters publicly ...available failed to reproduce the zinc ion coordination in the enzyme, we developed a new set of the hybrid bonded/nonbonded parameters for the zinc ion suitable for molecular modeling of the human DPP III, dynamics, and ligand binding. The parameters allowed exchange of the water molecules coordinating the zinc ion and proved to be robust enough to enable reliable modeling not only of human DPP III and its orthologues but also of the other zinc-dependent peptidases with the zinc ion coordination similar to that in dipeptidyl peptidases III, i.e., peptidases with the zinc ion coordinated with two histidines and one glutamate. The new parameters were tested on a set of 21 different systems comprising 8 different peptidases, 5 DPP III orthologues, thermolysin, neprilysin, and aminopeptidase N, and the results are summarized in the second part of the article.
Function of Circle of Willis Vrselja, Zvonimir; Brkic, Hrvoje; Mrdenovic, Stefan ...
Journal of cerebral blood flow and metabolism,
04/2014, Letnik:
34, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Nearly 400 years ago, Thomas Willis described the arterial ring at the base of the brain (the circle of Willis, CW) and recognized it as a compensatory system in the case of arterial occlusion. This ...theory is still accepted. We present several arguments that via negativa should discard the compensatory theory. (1) Current theory is anthropocentric; it ignores other species and their analog structures. (2) Arterial pathologies are diseases of old age, appearing after gene propagation. (3) According to the current theory, evolution has foresight. (4) Its commonness among animals indicates that it is probably a convergent evolutionary structure. (5) It was observed that communicating arteries are too small for effective blood flow, and (6) missing or hypoplastic in the majority of the population. We infer that CW, under physiologic conditions, serves as a passive pressure dissipating system; without considerable blood flow, pressure is transferred from the high to low pressure end, the latter being another arterial component of CW. Pressure gradient exists because pulse wave and blood flow arrive into the skull through different cerebral arteries asynchronously, due to arterial tree asymmetry. Therefore, CW and its communicating arteries protect cerebral artery and blood–brain barrier from hemodynamic stress.
Radiotherapy of pregnant cancer patients is not common, but when applied accurate assessment of the fetus dose is required, especially since the treatment planning systems are not able and do not ...allow accurate assessment of out-of-field doses. Proton therapy significantly reduces out-of-field doses, such as dose to the fetus, when compared to the photon radiotherapy techniques and as such could be promising for pregnant cancer patients.
Within this study Monte Carlo calculations are performed on the three different computational phantoms representing pregnant women, all in second trimester of pregnancy. Simplified proton beam to the pregnant women brain was modelled, and the total dose equivalent (normalized per target dose) to the fetus was calculated.
Between MCNPX and MCNP6.2 code versions we observed up to 6% difference. In this work 3 groups participated and the variation between the groups was 8% and 12% for MCNPX and MCNP6.2, respectively. Depending on the phantom used in the calculations the fetal dose was between 0.4 and 0.8 μSv/Gy. Major contribution to the total dose came from the neutrons, with only 20% of the dose coming from photons, while other particles have negligible contributions. Results of the total dose equivalent differ by factor of two, when different phantoms were used, due to geometrical and anatomical characteristics of mother and fetus position.
•Code versions agreed within 6% in the fetus absorbed dose calculation.•Variation between the groups was 8% and 12% for MCNPX and MCNP6.2•Fetal dose was between 0.4 and 0.8 μSv/Gy due to different geometries between phantoms.•No impact was observed for varying female and fetus tissue composition.
Dipeptidyl peptidase III (DPP III, EC 3.4.14.4) is a monozinc metalloexopeptidase that hydrolyzes dipeptides from the N-terminus of peptides consisting of three or more amino acids. Recently, DPP III ...has attracted great interest from scientists, and numerous studies have been conducted showing that it is involved in the regulation of various physiological processes. Since it is the only metalloenzyme among the dipeptidyl peptidases, we considered it important to study the process of binding and exchange of physiologically relevant metal dications in DPP III. Using fluorimetry, we measured the Kd values for the binding of Zn2+, Cu2+, and Co2+ to the catalytic site, and using isothermal titration calorimetry (ITC), we measured the Kd values for the binding of these metals to an additional binding site. The structure of the catalytic metal’s binding site is known from previous studies, and in this work, the affinities for this site were calculated for Zn2+, Cu2+, Co2+, and Mn2+ using the QM approach. The structures of the additional binding sites for the Zn2+ and Cu2+ were also identified, and MD simulations showed that two Cu2+ ions bound to the catalytic and inhibitory sites exchanged less frequently than the Zn2+ ions bound to these sites.
Nowadays, high-energy X-rays produced by medical linear accelerators (LINACs) are widely used in many Radiation Therapy (RT) centers. High-energy photons (> 8 MeV) produce undesired neutrons in the ...LINAC head which raise concerns about unwanted neutron dose to the patients and RT personnel. Regarding the significance of radiation protection in RT, it is important to evaluate photoneutron contamination inside the RT room. Unfortunately, neutron dosimeters used for this purpose have limitations that can under the best conditions cause to > 10% uncertainty. In addition to this uncertainty, the present Monte Carlo (MC) study introduces another uncertainty in measurements (nearly up to 20%) when neutron ambient dose equivalent (Hn*(10)) is measured at the patient table or inside the maze and the change in neutron energy is ignored. This type of uncertainty can even reach 35% if Hn*(10) is measured by dosimeters covered by a layer of 10B as converter. So, in these cases, neglecting the change in neutron energy can threaten the credibility of measured data and one should attend to this energy change in order to reduce measurement uncertainty to the possible minimum. This study also discusses the change in neutron spectra and Hn*(10) at the patient table caused by removing a typical RT room from MC simulations. Under such conditions, neutron mean energy (Ēn) overestimated by 0.2–0.4 MeV at the patient table. Neutron fluence (φn) at the isocenter (IC) was underestimated by 23–54% for different field sizes that caused Hn*(10) to be miscalculated up to 24%. This finding informs researchers that for accurate evaluation of Hn*(10) at the patient table, simulating the RT room is an effective parameter in MC studies.
•The MCNPX® code was used to simulate the photoneutron production in the head of a medical LINAC (Varian Clinac 2100C/D 18 MV).•Neutron ambient dose equivalent and energy spectrum were calculated for different field sizes at the patient table and inside the maze.•Neutron energy changed with field size and also detector location.•Neglecting the change in neutron energy lead to major uncertainty in dosimetry.•Neutron ambient dose equivalent at the patient table changed with removing Radiation Therapy room from simulations.
Abstract To evaluate applicability of Demirjian and Willems methods for calculating dental age of children in the Former Yugoslav Republic of Macedonia we analyzed panoramic radiographs of 966 ...children (485 female and 481 male, aged 6–13 years) treated at the University and Community Dental Clinics in Skopje using four Demirjian methods and a Willems method for determining dental ages. Intra-rater and inter-rater agreement of mineralization stages were 0.86 and 0.82, respectively. All methods significantly overestimated dental age when compared to the chronological age ( p < 0.001). In males, the lowest overestimation was shown using Willems method (0.52 ± 0.87 years), followed by Demirjian methods from 1976 using PM1 , PM2 , M1 , M2 teeth (0.69 ± 0.92 years) and using I2 , PM1 , PM2 , M2 teeth (0.80 ± 0.98 years). The greatest overestimation were shown using Demirjian methods using 7 teeth from 1976 (0.92 ± 0.99 years) and method from 1973 (1.06 ± 1.07 years). In females, the lowest overestimation was shown using Willems method (0.33 ± 0.83 years) than the Demirjian method using PM1 , PM2 , M1 , M2 teeth (1.00 ± 1.01 years), following methods from 1976 using 7 teeth (1.03 ± 1.01 years) and I2 , PM1 , PM2 , M2 teeth (1.12 ± 0.96 years). The greatest overestimation was for method from 1973 using 7 teeth (1.17 ± 0.98 years). Willems method was the most accurate while Demirjian's methods for dental age calculation are not suitable on children from the Former Yugoslav Republic of Macedonia.
Dipeptidyl peptidase III (DPP III), a zinc-dependent exopeptidase, is widely distributed in organisms and present in almost all human tissues. In addition to its involvement in protein catabolism, it ...plays a role in oxidative stress and blood pressure regulation, and there is evidence of its involvement in pain modulation. Excess zinc ions have been found to inhibit its hydrolytic activity, but the binding affinity, binding site geometry, and mechanism of inhibitory activity have been unknown. Using several different computational approaches, we determined the inhibitory zinc ion binding site, its coordination and relative binding affinity. During some simulations the translocation of the zinc ion from the inhibitory to the catalytic binding site was observed, accompanied by movement of the catalytic zinc ion toward the exit of the substrate binding site. The traced behavior suggests an associative type of metal ion exchange, in which the formation of the ternary complex between enzyme and two metal ions precedes the exit of the catalytic metal ion. Differently from our previous findings that binding of a peptide induces partial opening of hDPP III, the globularity of the protein did not change in MD simulations of the hermorphin-like peptide bound to hDPP III with two zinc ions. However, the entrance to the interdomain cleft widens during Zn diffusion into the protein and was found to be the highest energy barrier in the process of metal translocation from the solvent to the active site. Finally, we discuss why excess zinc reduces enzyme activity.
The binding of two Zn ions to human DPP III was investigated. Simulations showed translocation of Zn ion from the inhibitory to the catalytic binding site, accompanied by displacement of the catalytic Zn from the interdomain cleft.
Dipeptidyl peptidase 3 (DPP3) is a zinc-dependent exopeptidase with broad specificity for four to eight amino acid residue substrates. It has a role in the regulation of oxidative stress response ...NRF2–KEAP1 pathway through the interaction with KEAP1. We have conducted stable isotope labeling by amino acids in a cell culture coupled to mass spectrometry (SILAC-MS) interactome analysis of TRex HEK293T cells using DPP3 as bait and identified SH2 Domain-Containing Protein 3C (SH2D3C) as prey. SH2D3C is one of three members of a family of proteins that contain both the SH2 domain and a domain similar to guanine nucleotide exchange factor domains of Ras family GTPases (Ras GEF-like domain), named novel SH2-containing proteins (NSP). NSPs, including SH2D3C (NSP3), are adaptor proteins involved in the regulation of adhesion, migration, tissue organization, and immune response. We have shown that SH2D3C binds to DPP3 through its C-terminal Ras GEF-like domain, detected the colocalization of the proteins in living cells, and confirmed direct interaction in the cytosol and membrane ruffles. Computational analysis also confirmed the binding of the C-terminal domain of SH2D3C to DPP3, but the exact model could not be discerned. This is the first indication that DPP3 and SH2D3C are interacting partners, and further studies to elucidate the physiological significance of this interaction are on the way.
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