Genetic dissection of the biochemical activities of human DNA repair protein, APE1

Human apurinic/apyrimidinic endonuclease 1 (APE1) is a key DNA repair enzyme involved in both base excision repair (BER) and nucleotide incision repair (NIR) pathways. In the BER pathway, APE1 cleaves DNA at AP sites and 3'-blocking moieties generated by DNA glycosylases. In the NIR pathway, APE1 incises DNA 5' to a number of oxidatively damaged bases. Here we propose to identify and characterize critical amino acids of APE1 involved in either BER and/or NIR functions by using the alignment of the known three-dimensional (or tertiary) structures of Xth family AP endonucleases including the Methanothermobacter thermautotrophicus Mth212, Bacillus subtilis ExoA (1), E. coli Xth and human APE1 proteins (2)

Genetic dissection of the biochemical activities of human DNA repair protein, APE1

Human apurinic/apyrimidinic endonuclease 1 (APE1) is a key DNA repair enzyme involved in both base excision repair (BER) and nucleotide incision repair (NIR) pathways. In the BER pathway, APE1 cleaves DNA at AP sites and 3'-blocking moieties generated by DNA glycosylases. In the NIR pathway, APE1 incises DNA 5' to a number of oxidatively damaged bases. Here we propose to identify and characterize critical amino acids of APE1 involved in either BER and/or NIR functions by using the alignment of the known three-dimensional (or tertiary) structures of Xth family AP endonucleases including the Methanothermobacter thermautotrophicus Mth212, Bacillus subtilis ExoA (1), E. coli Xth and human APE1 proteins (2)

Development and testing of new force fields for molecular dynamics simulations

Recent progress in modeling of protein folding in Dr. Shaw laboratory has been achieved only after some improvements of potentials of covalent forces, taken from the standard AMBER force field; and still, the force field used is not quite satisfactory to reproduce folded structures of some larger proteins, having significant, about 5A, RMS deviation between the computed and experimentally determined 3D structures. The objective of this research is to develop and test new polarizable atomic force fields (FFs) for "in-vacuum" and "in-water" non-bonded interactions based on AMBER ff99SBILDN force fields, improved by inclusion of new terms. FFs parameter optimization will be done using our set of molecular crystals with crystallographic data from the Cambridge Structural Database and sublimation/solvation thermodynamics characteristics from various sources

One-Dimensional Impenetrable Anyons in Thermal Equilibrium. II. Determinant Representation for the Dynamic Correlation Functions

We have obtained a determinant representation for the time- and temperature-dependent field-field correlation function of the impenetrable Lieb-Liniger gas of anyons through direct summation of the form factors. In the static case, the obtained results are shown to be equivalent to those that follow from the anyonic generalization of Lenard's formula.Comment: 16 pages, RevTeX

История и опыт трансплантации почки в Узбекистане

This paper presents a brief outline of the history of transplantation service in the Republic of Uzbekistan, which originated at the country’s Center for Kidney Transplantation. The role played by outstanding scientists in Uzbekistan, their works and efforts towards the creation of a separate area of clinical and scientific medicine in Uzbekistan, are highlighted. Achievements by the research school of U.A. Aripov, Academician of the Academy of Sciences of the Republic of Uzbekistan, who performed the first successful kidney transplantation in 1972, are shown. The ups and downs of national transplantation nephrology, as well as the birth of a national school of kidney transplantation, domiciled at the Vakhidov Republican Specialized Scientific and Practical Medical Center of Surgery, headed by academician F.G. Nazirov, and giving a stimulus to the «second breath» of the national school of transplantology, is reflected. Separate attention is devoted to the actual problems of national transplantology, moral, ethical and regulatory issues that inevitably accompany this scientific and clinical direction are reflected. Kidney transplant outcomes in Uzbekistan are given, the prospects for further scientific and clinical directions are indicated.В данной работе представлен краткий очерк истории развития трансплантационной службы в РУз, зародившейся в Центре трансплантации почки АН РУз. Освещена роль выдающихся ученых Узбекистана, их труды и усилия на пути создания отдельного направления клинической и научной медицины в РУз. Показаны достижения научной школы академика АН Республики Узбекистан У.А. Арипова, выполнившего в 1972 г. первую успешную трансплантацию почки. Отражены взлеты и падения отечественной службы трансплантационной нефрологии, а также зарождение отечественной школы трансплантации почки в Государственном учреждении «Республиканский специализированный научно-практический медицинский центр хирургии (РСНПМЦХ) имени академика В. Вахидова» во главе с академиком Ф.Г. Назировым, придавшей стимул «второго дыхания» отечественной трансплантологической школе. Отдельное внимание обращено на актуальные проблемы отечественной трансплантологии, отражены морально-этические и нормативно правовые вопросы, неизбежно сопровождающие указанное научно-клиническое направление. Приведены результаты трансплантации почки в Узбекистане, обозначены перспективы дальнейших научных и клинических направлений

Aberrant DNA glycosylase-initiated repair pathway of free radicals induced DNA damage: implications for age-related diseases and natural aging

Aerobic cellular respiration generates reactive oxygen species (ROS), which can damage macro-molecules including lipids, proteins and DNA. It was proposed that aging is a consequence of accumulation of naturally occurring unrepaired oxidative DNA damage. In human cells, approximately 2000 to 8000 DNA lesions occur per hour in each cell, i.e. 40000 to 200000 per cell per day. DNA repair systems are able to discriminate between regular and modified bases. For example, DNA glycosylases specifically recognize and excise damaged bases among vast majority of regular bases in the base excision repair (BER) pathway. However, mismatched pairs between two regular bases occur due to spontaneous conversion of 5-methylcytosine to thymine and DNA polymerase errors during replication. To counteract these mutagenic threats to genome stability, cells evolved special DNA repair systems that target the non-damaged DNA strand in a duplex to remove mismatched regular DNA bases. Base excision repair (BER) and mismatch repair (MMR) pathways initiated by mismatch-specific adenine- and thymine-DNA glycosylases (MutY/MUTYH and TDG/MBD4, respectively) can recognize and remove normal DNA bases in mismatched DNA duplexes. Under certain circumstances in DNA repair deficient cells bacterial MutY and human TDG can act in an aberrant manner: MutY and TDG remove Adenine and Thymine opposite to misincorporated 8-oxoguanine and damaged Adenine, respectively. These unusual activities lead either to mutations or futile DNA repair, thus indicating that the DNA repair pathways which target non-damaged DNA strand can act in an aberrant manner and introduce genome instability in the presence of unrepaired DNA lesions. Both accumulation of oxidative DNA damage in cells and the aberrant DNA repair can contribute to cancer, brain disorders and premature senescence

Prediction of the protein conformation via pattern recognition and constraint satisfaction methods

The prediction of the native structure of proteins given their amino acid sequence is one of the central problems in modern computational biology/biophysics/biochemistry and computer science. Today there are more than 80000 3D structures of various biomacromolecules in the open access, e.g. in Protein Data Bank (PDB), and these databases have exponential growth rate. The project goal is to design and implement computing experiments related to biomacromolecular folding. This includes the development of high performance bioinformatics software

Prediction of the protein conformation via pattern recognition and constraint satisfaction methods

The prediction of the native structure of proteins given their amino acid sequence is one of the central problems in modern computational biology/biophysics/biochemistry and computer science. Today there are more than 80000 3D structures of various biomacromolecules in the open access, e.g. in Protein Data Bank (PDB), and these databases have exponential growth rate. The project goal is to design and implement computing experiments related to biomacromolecular folding. This includes the development of high performance bioinformatics software

THE INFLUENCE OFFERTILIZER STANDARDSON THE GRAIN QUALITY OF FRESH AND PERSPECTIVE WHEAT SORT

In this article the influence of mineral fertilizers on the winter wheat yields is highlighted. It was determined that biometric data of winter wheat sorts were high when the norms of mineral fertilizers were in variantsof N200; P-120; K-120k

Internet data accumulation and processing complex

A language corpus is a collection of texts written in that language and classified by genres. Corpora are actively used by researchers from different fields (most notably linguists and computer scientists) and by industry (Google, Yandex, etc.