Papers by Alexander Pozhitkov
Springer eBooks, 2003
The comparative study of the behavior of DsRed1, EYFP and ECFP under high pressure was carried ou... more The comparative study of the behavior of DsRed1, EYFP and ECFP under high pressure was carried out. We found that only chromophores of EYFP and ECFP were sensitive to pressure treatment. The result is interesting from the point of view of high structural similarity of DsRed1 and other studied proteins leading to the discovery of new properties in high pressure studies that wouldn’t show up otherwise.
Clinical Lymphoma Myeloma and Leukemia
Quantitative Biology, 2018
JDR Clinical & Translational Research, 2019
Nucleic Acids Research, 2007
Journal of Microbiological Methods, 2008
Applied and Environmental Microbiology, 2005
Past studies have suggested that thermal dissociation analysis of nucleic acids hybridized to DNA... more Past studies have suggested that thermal dissociation analysis of nucleic acids hybridized to DNA microarrays would improve discrimination among duplex types by scanning through a broad range of stringency conditions. To more fully constrain the utility of this approach using a previously described gel-pad microarray format, artificial neural networks (NNs) were trained to recognize noisy or low-quality data, as might derive from nonspecific fluorescence, poor hybridization, or compromised data collection. The NNs were trained to classify dissociation profiles (melts) into groups based on selected characteristics (e.g., initial signal intensity, area under the curve) using a data set of 21,044 profiles derived from 186 probes hybridized to a study set of RNA extracted from 32 microbes common to the human oral cavity. Three melt profile groups were identified: one group consisted mostly of ideal melt profiles; another group consisted mostly of poor melt profiles; and, the remainder w...
Background. The American Society of Anesthesiologists (ASA) Physical Status Classification System... more Background. The American Society of Anesthesiologists (ASA) Physical Status Classification System defines peri-operative patient scores as 1 (healthy) thru 6 (brain dead). The scoring is used by the anesthesiologists to classify surgical patients based on co-morbidities and various clinical characteristics. The classification is always done by an anesthesiologist prior operation. There is a variability in scoring stemming from individual experiences / biases of the scoring anesthesiologists, which impacts prediction of operating times, length of stay in the hospital, necessity of blood transfusion, etc. In addition, the score affects anesthesia coding and billing. It is critical to remove subjectivity from the process to achieve reproducible generalizable scoring. Methods. A machine learning (ML) approach was used to associate assigned ASA scores with peri-operative patients' clinical characteristics. More than ten ML algorithms were simultaneously trained, validated, and tested...
International Journal of Oncology
The post-translational modification of proteins by ubiquitinating enzymes plays a central role in... more The post-translational modification of proteins by ubiquitinating enzymes plays a central role in a number of cellular functions, such as cell proteolysis, DNA repair, and cell signaling and communication. Deubiquitinating enzymes (DUBs) disassemble ubiquitin chains and remove ubiquitin moieties from proteins. Targeting DUBs in cancer models has revealed an important role for these enzymes in tumorigenesis, and they therefore have emerged as attractive therapeutic targets. In the present study, the effects of three DUB inhibitors, PR-619, RA-9 and LDN-91946, on a non-small cell lung cancer cell line (A549) and a mesothelioma cell line (H2373) were investigated. PR-619 significantly inhibited cell adhesion and the proliferation of both cell lines. RA-9 exerted an inhibitory effect on the adhesion and proliferation of H2373 cells, whereas it had no effect on A549 cells. Notably, however, while PR-619 attenuated the proliferation of both cell lines, it exerted an opposite effect on cell motility; in the case of A549 cells, there was a significant increase in cell motility, while for the H2373 cells, there was a significant decrease. Furthermore, protein phosphorylation kinetic analyses revealed that the effects were cell line-specific. In H2373 cells, the phosphorylation of only one peptide corresponding to the P85A protein was significantly affected, and while LDN-91946 treatment increased phosphorylation, treatment with RA-9 or PR-619 decreased its phosphorylation compared to the DMSO control. By contrast, in the case of A549 cells, the phosphorylation of 21 peptides was significantly affected by the same compounds. In light of the potential for the negative side-effects of DUB inhibition, such as increased cancer cell motility, the data presented herein underscore the dire need for the development of specific DUB inhibitors and to elucidate the individual role of DUB family members in cancer biology before they can be specifically pharmacologically targeted.
The Biochemist
In life, most internal organs of a healthy adult vertebrate are essentially ‘microbial-cell-free’... more In life, most internal organs of a healthy adult vertebrate are essentially ‘microbial-cell-free’ – but in death, microorganisms invade and proliferate these internal organs and genes are expressed by the host presumably in response. We recently investigated how these two interconnected processes change with postmortem time and examined the feasibility of using this information to determine the postmortem interval, i.e. the elapsed-time-since-death. Although more research is needed, our findings suggest one of them has a significant potential to determine the length of time from the person dying until discovery of the body.
Blood Advances
Key Points Teriflunomide, the active metabolite of leflunomide, downregulates c-Myc expression th... more Key Points Teriflunomide, the active metabolite of leflunomide, downregulates c-Myc expression through inhibition of PIM kinases. Leflunomide together with lenalidomide significantly extended survival in an in vivo MM model.
ABSTRACTOur previous study found more than 500 transcripts significantly increased in abundance i... more ABSTRACTOur previous study found more than 500 transcripts significantly increased in abundance in the zebrafish and mouse several hours to days postmortem relative to live controls. The current literature suggests that most mRNAs are post-transcriptionally regulated in stressful conditions, we rationalized that the postmortem transcripts must contain sequence features (3 to 9 mers) that are unique from those in the rest of the transcriptome – specifically, binding sites for proteins and/or non-coding RNAs involved in regulation. Our new study identified 5117 and 2245 over-represented sequence features in the mouse and zebrafish, respectively. Some of these features were disproportionately distributed along the transcripts with high densities in the 3-UTR region of the zebrafish (0.3 mers/nt) and the ORFs of the mouse (0.6 mers/nt). Yet, the highest density (2.3 mers/nt) occurred in the ORFs of 11 mouse transcripts that lacked UTRs. Our results suggest that these transcripts might s...
Clinical Implant Dentistry and Related Research
BACKGROUND Recent data support the implication of accelerated titanium dissolution products in pe... more BACKGROUND Recent data support the implication of accelerated titanium dissolution products in peri-implantitis. It is unknown whether these dissolution products have an effect on the peri-implant microbiome, the target of existing peri-implantitis therapies. PURPOSE This study assessed the relationship between the peri-implant microbiome, dissolved titanium levels, and peri-implantitis. MATERIALS AND METHODS Clinical, microbiome, and titanium data were collected from a periodontal population having implants in function for 10 years. Clinical examinations were performed, and submucosal plaque samples were collected from the deepest site per implant. An aliquot of the sample was used for 16S rRNA gene sequencing, with the remainder analyzed for titanium quantity using mass spectrometry. Sequences were clustered into taxonomic units at 97% minimum sequence similarity using the QIIME pipeline approach. RESULTS Fifteen implants were assessed. According to established case definitions, six had a diagnosis of peri-implantitis; nine were healthy. The genera Streptococcus, Prevotella and Haemophilus characterized peri-implant health. Peri-implantitis was associated with a marked increase in Veillonella. Quantities of dissolved titanium were identified in 40% of sites. Titanium presence was associated with peri-implant disease status (P = .02) and correlated to the first principal component of the microbiome (rho = 0.552) and its alpha-diversity (rho = -0.496). Canonical correlation analyses found that titanium levels, but not health or disease status of the implant, were significantly associated with the microbiota composition (P = .045). CONCLUSIONS These findings suggest an association between titanium dissolution products and peri-implantitis and support a role for these products in modifying the peri-implant microbiome structure and diversity.
BMC genomics, Jan 14, 2018
Our previous study found that more than 500 transcripts significantly increased in abundance in t... more Our previous study found that more than 500 transcripts significantly increased in abundance in the zebrafish and mouse several hours to days postmortem relative to live controls. The current literature suggests that most mRNAs are post-transcriptionally regulated in stressful conditions. We rationalized that the postmortem transcripts must contain sequence features (3- to 9- mers) that are unique from those in the rest of the transcriptome and that these features putatively serve as binding sites for proteins and/or non-coding RNAs involved in post-transcriptional regulation. We identified 5117 and 2245 over-represented sequence features in the mouse and zebrafish, respectively, which represents less than 1.5% of all possible features. Some of these features were disproportionately distributed along the transcripts with high densities in the 3' untranslated regions of the zebrafish (0.3 mers/nt) and the open reading frames of the mouse (0.6 mers/nt). Yet, the highest density (2...
Communicative & Integrative Biology
BioEssays
After a vertebrate dies, many of its organ systems, tissues, and cells remain functional while it... more After a vertebrate dies, many of its organ systems, tissues, and cells remain functional while its body no longer works as a whole. We define this state as the "twilight of death" - the transition from a living body to a decomposed corpse. We claim that the study of the twilight of death is important to ethical, legal and medical science. We examined gene expression at the twilight of death in the zebrafish and mouse reaching the conclusion that apparently thousands of transcripts significantly increase in abundance from life to several hours/days postmortem relative to live controls. Transcript dynamics of different genes provided "proof-of-principle" that models accurately predict an individual's elapsed-time-of-death (i.e. postmortem interval). While many transcripts were associated with survival and stress compensation, others were associated with epigenetic factors, developmental control, and cancer. Future studies are needed to determine whether the high incidence of cancer in transplant recipients is due to the postmortem processes in donor organs.
Open biology, 2017
In life, genetic and epigenetic networks precisely coordinate the expression of genes-but in deat... more In life, genetic and epigenetic networks precisely coordinate the expression of genes-but in death, it is not known if gene expression diminishes gradually or abruptly stops or if specific genes and pathways are involved. We studied this by identifying mRNA transcripts that apparently increase in relative abundance after death, assessing their functions, and comparing their abundance profiles through postmortem time in two species, mouse and zebrafish. We found mRNA transcript profiles of 1063 genes became significantly more abundant after death of healthy adult animals in a time series spanning up to 96 h postmortem. Ordination plots revealed non-random patterns in the profiles by time. While most of these transcript levels increased within 0.5 h postmortem, some increased only at 24 and 48 h postmortem. Functional characterization of the most abundant transcripts revealed the following categories: stress, immunity, inflammation, apoptosis, transport, development, epigenetic regula...
In life, genetic and epigenetic networks precisely coordinate the expression of genes—but in deat... more In life, genetic and epigenetic networks precisely coordinate the expression of genes—but in death, it is not known if gene expression diminishes gradually or abruptly stops or if specific genes and pathways are involved. We studied this by identifying mRNA transcripts that apparently increase in relative abundance after death, assessing their functions, and comparing their abundance profiles through postmortem time in two species, mouse and zebrafish. We found mRNA transcript profiles of 1063 genes became significantly more abundant after death of healthy adult animals in a time series spanning up to 96 h postmortem. Ordination plots revealed non-random patterns in the profiles by time. While most of these transcript levels increased within 0.5 h postmortem, some increased only at 24 and 48 h postmortem. Functional characterization of the most abundant transcripts revealed the following categories: stress, immunity, inflammation, apoptosis, transport, development, epigenetic regula...
Uploads
Papers by Alexander Pozhitkov