Viruses with U-DNA : New Avenues for Biotechnology

Deoxyuridine in DNA has recently been in the focus of research due to its intriguing roles in several physiological and pathophysiological situations. Although not an orthodox DNA base, uracil may appear in DNA via either cytosine deamination or thymine-replacing incorporations. Since these alterations may induce mutation or may perturb DNA-protein interactions, free living organisms from bacteria to human contain several pathways to counteract uracilation. These efficient and highly specific repair routes uracil-directed excision repair initiated by representative of uracil-DNA glycosylase families. Interestingly, some bacteriophages exist with thymine-lacking uracil-DNA genome. A detailed understanding of the strategy by which such phages can replicate in bacteria where an efficient repair pathway functions for uracil-excision from DNA is expected to reveal novel inhibitors that can also be used for biotechnological applications. Here, we also review the several potential biotechnological applications already implemented based on inhibitors of uracil-excision repair, such as Crispr-base-editing and detection of nascent uracil distribution pattern in complex genomes.Peer reviewe

Viruses with U-DNA : New Avenues for Biotechnology

Deoxyuridine in DNA has recently been in the focus of research due to its intriguing roles in several physiological and pathophysiological situations. Although not an orthodox DNA base, uracil may appear in DNA via either cytosine deamination or thymine-replacing incorporations. Since these alterations may induce mutation or may perturb DNA-protein interactions, free living organisms from bacteria to human contain several pathways to counteract uracilation. These efficient and highly specific repair routes uracil-directed excision repair initiated by representative of uracil-DNA glycosylase families. Interestingly, some bacteriophages exist with thymine-lacking uracil-DNA genome. A detailed understanding of the strategy by which such phages can replicate in bacteria where an efficient repair pathway functions for uracil-excision from DNA is expected to reveal novel inhibitors that can also be used for biotechnological applications. Here, we also review the several potential biotechnological applications already implemented based on inhibitors of uracil-excision repair, such as Crispr-base-editing and detection of nascent uracil distribution pattern in complex genomes.Peer reviewe

Probing pattern and dynamics of disulfide bridges using synthesis and NMR of an ion channel blocker peptide toxin with multiple diselenide bonds

Anuroctoxin (AnTx), a 35-amino-acid scorpion toxin containing four disulfide bridges, is a high affinity blocker of the voltage-gated potassium channel Kv1.3, but also blocks Kv1.2. To improve potential therapeutic use of the toxin, we have designed a double substituted analog, [N17A/F32T]-AnTx, which showed comparable Kv1.3 affinity to the wild-type peptide, but also a 2500-fold increase in the selectivity for Kv1.3 over Kv1.2. In the present study we have achieved the chemical synthesis of a Sec-analog in which all cysteine (Cys) residues have been replaced by selenocysteine (Sec) forming four diselenide bonds. To the best of our knowledge this is the first time to replace, by chemical synthesis, all disulfide bonds with isosteric diselenides in a peptide/protein. Gratifyingly, the key pharmacological properties of the Sec-[N17A/F32T]-AnTx are retained since the peptide is functionally active. We also propose here a combined experimental and theoretical approach including NOE- and Se-77-based NMR supplemented by MD simulations for conformational and dynamic characterization of the Sec-[N17A/F32T]-AnTx. Using this combined approach allowed us to attain unequivocal assignment of all four diselenide bonds and supplemental MD simulations allowed characterization of the conformational dynamics around each disulfide/diselenide bridge

Nevus Sebaceous with Multiple Basal Cell Carcinomas and Extracutaneous Abnormalities: Genetic Origin or Coincidence?

The association of cutaneous and extracutaneous abnormalities is a common phenomenon, widely described in a variety of genetic syn- dromes. Nevertheless, yet undescribed syndromic combinations may still exist. Herein we present a case report of a patient who was admitted to the Dermatology Department due to multiple basal cell carcinomas arising from nevus sebaceous. In addition to the cutaneous malignancies, the patient presented with palmoplantar keratoderma, prurigo nodularis, hypothyroid- ism, multiple lumbar abnormalities, uterine myoma, an ovarian cyst, and highly dysplastic colon adenoma. Such a combination of multiple disorders may indicate a genetic origin of the diseases

Nevus Sebaceous with Multiple Basal Cell Carcinomas and Extracutaneous Abnormalities: Genetic Origin or Coincidence?

The association of cutaneous and extracutaneous abnormalities is a common phenomenon, widely described in a variety of genetic syn- dromes. Nevertheless, yet undescribed syndromic combinations may still exist. Herein we present a case report of a patient who was admitted to the Dermatology Department due to multiple basal cell carcinomas arising from nevus sebaceous. In addition to the cutaneous malignancies, the patient presented with palmoplantar keratoderma, prurigo nodularis, hypothyroid- ism, multiple lumbar abnormalities, uterine myoma, an ovarian cyst, and highly dysplastic colon adenoma. Such a combination of multiple disorders may indicate a genetic origin of the diseases

TOURISM IN THE CENTRE REGION, BETWEEN STATISTICAL COORDINATES AND MASTER PLAN TARGETS

The Central Region Development Strategy has as its principal objective the balanced development of the Centre Region through economic growth, the utilization of existing natural resources and the protection of the environment. Depending on the proposed objectives, the Centre Region must obtain funds for Regional projects included in the Regional Development Plan. Realising funding of these projects will greatly contribute to achieving the objectives set out in the Europe 2020 strategy.

A tuberkulózis előfordulása egy XVIII. századi váci családban

Two individuals of the Nigrovits family from the Vác Mummy Collection of the Hungarian Natural History Museum were the subjects of multidisciplinary, anthropological, paleopathological, radiological, paleomicrobiological and paleoproteomic studies. The father, József Nigrovits (No 29), died at the age of 55 on the 11th of November 1793; his son, Antal Nigrovits (No 54), died on the 16th of July 1803, at the age of 22. They lived in the 18th century in a small town of northern Hungary. The macroscopic examination of body No 54 showed a severely deformed neck and back region; body No 29 had no characteristic marks of any illnesses. The CT scan data of the bodies and their 3D reconstructions showed no skeletal evidence of tuberculosis, despite the positive results of their paleomicrobiological studies. The deformity of body No 54 turned to be a developmental abnormality of unknown origin, but no Pott’s gibbus was present

2,4-diphenylthiophene induces mainly base pair mutation in Salmonella Typhimurium

Heterocyclic aromatic compounds containing sulfur (S-HET), have been detected in air, soil, marine environment and freshwater sediment. Toxicity and mutagenicity data of this class of substances are scarce. The present study focuses on implications of two aryl thiophenes and their mutagenic properties in Salmonella/microsome test. In our experiment only 2,4-diphenylthiophene showed little mutagenic effect in both variants of activaction (+/-S9) in strain TA100. Thiophene ring joined to K-region of phenanthrene did not change the biological activity of 3,6-dimetoxyphenanthro [9,10-c]thiophene and this compound did not show mutagenic potency

Mutagenicity induced in Salmonella strains TA98 and TA100 by diphenylthiophenes

Mutagenic properties of four different diphenylthiophenes: 3,4-diphenylthiophene, 3,4-di(4'-methylphenyl)thiophene, 3,4-di(4'-methoxyphenyl)thiophene and 3,4-di(4'-pentoxyphenyl)thiophene were investigated applying the Salmonella test. The research was done on two strains of Salmonella Typhimurium: TA98 and TA100, tested in two variants: with (+S9) and without (-S9) enzymatic activation. Only one compound 3,4-di(4'-methylphenyl)thiophene showed mutagenic activity when studied with metabolic activation (+S9) and its mutagenic rate (MR) score was 3.41 for the dose of 10.00µg*plate-1. Other studied compounds did not show any mutagenic activity (+/-S9) and their MR score did not exceed the threshold value of 2.0

Physical properties of thermoelectric zinc antimonide using first-principles calculations

We report first principles calculations of the structural, electronic, elastic and vibrational properties of the semiconducting orthorhombic ZnSb compound. We study also the intrinsic point defects in order to eventually improve the thermoelectric properties of this already very promising thermoelectric material. Concerning the electronic properties, in addition to the band structure, we show that the Zn (Sb) crystallographically equivalent atoms are not exactly equivalent from the electronic point of view. Lattice dynamics, elastic and thermodynamic properties are found to be in good agreement with experiments and they confirm the non equivalency of the zinc and antimony atoms from the vibrational point of view. The calculated elastic properties show a relatively weak anisotropy and the hardest direction is the y direction. We observe the presence of low energy modes involving both Zn and Sb atoms at about 5-6 meV, similarly to what has been found in Zn4Sb3 and we suggest that the interactions of these modes with acoustic phonons could explain the relatively low thermal conductivity of ZnSb. Zinc vacancies are the most stable defects and this explains the intrinsic p-type conductivity of ZnSb.Comment: 33 pages, 8 figure