114 results on '"Andrey Frolov"'
Search Results
2. Dung-beetles (Coleoptera, Scarabaeidae, Aphodiinae, Scarabaeinae) feeding on faeces of steppe marmots Marmota bobak (Rodentia, Sciuridae) in Middle Volga territory
- Author
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Lilia Akhmetova, Andrei Kurochkin, and Andrey Frolov
- Subjects
steppe marmot ,ground squirrels ,keystone species ,Biology (General) ,QH301-705.5 - Abstract
In open terrestrial biomes of Holarctic realm, ground squirrels are recognised as keystone species inhabiting steppes. They shape the plant species composition and diversity and support a fauna of species associated with their burrows. Ground squirrels and associated dung-beetles are important elements of the steppe food webs, yet the trophic associations between species are still poorly studied.The area in the northern outskirts of Obshchy Syrt plateau, on the border of Samara and Orenburg Provinces of Russia was surveyed and scarab beetles (Scarabaeidae) feeding on steppe marmot (Marmota bobak (Müller, 1776)) faeces were collected from six localities. Twenty eight species of two subfamilies – Aphodiinae and Scarabaeinae, - were identified with the majority of species belonging the genus Aphodius Hellwig, 1798. Seven species are recorded as consumers of marmot faeces for the first time. Only two nidicolous specialist species were found which suggests that the studied population of steppe marmots is as result of the recent secondary colonisation and not all the associated scarab beetle faunas were re-established.
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- 2024
- Full Text
- View/download PDF
3. Sex-Related Pain Behavioral Differences following Unilateral NGF Injections in a Rat Model of Low Back Pain
- Author
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Michael Syrett, Nicholas R. Reed, William R. Reed, Madison L. Richey, Andrey Frolov, and Joshua W. Little
- Subjects
sex differences ,females ,nerve growth factor ,low back pain ,musculoskeletal pain ,mechanical hypersensitivity ,Biology (General) ,QH301-705.5 - Abstract
Low back pain (LBP) is a globally prevalent and costly societal problem with multifactorial etiologies and incompletely understood pathophysiological mechanisms. To address such shortcomings regarding the role of neurotrophins in the underlying mechanisms of pain, an LBP model was developed in rats involving two unilateral intramuscular injections of nerve growth factor (NGF) into deep trunk muscles. To date, behavioral investigations of this NGF-LBP model have been limited, especially as it pertains to female pain behaviors. This study compared mechanical sensitivity to noxious (hyperalgesia) and non-noxious (hypersensitivity) stimuli in control and NGF-injected male and female rats through pain resolution. Although the baseline testing revealed no differences between males and females, NGF-injected females demonstrated prolonged ipsilateral deep trunk mechanical hyperalgesia that resolved seven days later than males. Moreover, females showed bilateral trunk mechanical sensitivity to noxious and non-noxious stimuli compared to only ipsilateral behaviors in males. Sex differences were also observed in the severity of behavioral responses, with females displaying greater mean differences from baseline at several timepoints. Overall, these NGF-LBP behavioral findings mirror some of the sex differences reported in the clinical presentation of LBP and accentuate the translatability of this NGF-LBP model. Future studies using this LBP-NGF model could help to elucidate the neurobiological mechanisms responsible for the development, severity, and/or resolution of muscular LBP as well as to provide insights into the processes governing the transition from acute to chronic LBP.
- Published
- 2022
- Full Text
- View/download PDF
4. Sagittal Craniosynostosis with Uncommon Anatomical Pathologies in a 56-Year-Old Male Cadaver
- Author
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Andrey Frolov, Craig Lawson, Joshua Olatunde, James T. Goodrich, and John R. Martin III
- Subjects
Pathology ,RB1-214 - Abstract
Sagittal craniosynostosis (CS) is a pathologic condition that results in premature fusion of the sagittal suture, restricting the transverse growth of the skull leading in some cases to elevated intracranial pressure and neurodevelopmental delay. There is still much to be learned about the etiology of CS. Here, we report a case of 56-year-old male cadaver that we describe as sagittal CS with torus palatinus being an additional anomaly. The craniotomy was unsuccessful (cephalic index, CI = 56) and resulted in abnormal vertical outgrowth of the craniotomized bone strip. The histological analysis of the latter revealed atypical, noncompensatory massive bone overproduction. Exome sequencing of DNA extracted from the cadaveric tissue specimen performed on the Next Generation Sequencing (NGS) platform yielded 81 genetic variants identified as pathologic. Nine of those variants could be directly linked to CS with five of them targeting RhoA GTPase signaling, with a potential to make it sustained in nature. The latter could trigger upregulated calvarial osteogenesis leading to premature suture fusion, skull bone thickening, and craniotomized bone strip outgrowth observed in the present case.
- Published
- 2019
- Full Text
- View/download PDF
5. A Rare Case of Human Diphallia Associated with Hypospadias
- Author
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Andrey Frolov, Yun Tan, Mohammed Waheed-Uz-Zaman Rana, and John R. Martin
- Subjects
Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Diphallia or penile duplication is a rare congenital variant with an estimated frequency of 1 per 5 to 6 million live births. The extent of duplication varies widely and typically occurs with other malformations including urogenital, gastrointestinal, and musculoskeletal anomalies. Here we present a case of human diphallia that was detected during routine dissection of an 84-year-old cadaver. Upon thorough examination, this case was characterized as a complete bifid penis which was accompanied by hypospadias with no other anatomical abnormalities detected. To gain insights into the etiology of this case, we analyzed DNA procured from the body for putative genetic variants using Next Generation Sequencing (NGS) technology. Our results support clinical observations consistent with human diphallia being a polygenic syndrome and identify new genetic variants that might underlie its etiology.
- Published
- 2018
- Full Text
- View/download PDF
6. New data on the rare Afrotropical scarab beetles Orphnus drumonti Frolov and Delopleurus naviauxi Frolov et Cambefort (Coleoptera, Scarabaeidae, Orphninae and Scarabaeinae)
- Author
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Andrey Frolov and Lilia Akhmetova
- Subjects
Scarab beetles ,scarabaeines ,orphnines ,new locality record ,description ,Africa ,Afrotropical Region ,Democratic Republic of Congo ,Tanzania ,Biology (General) ,QH301-705.5 - Published
- 2015
- Full Text
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7. Little known Orphninae (Coleoptera, Scarabaeidae) collected by the Madagascan expeditions of the California Academy of Sciences
- Author
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Andrey Frolov
- Subjects
Scarab beetles ,orphnines ,new species ,Madecorphnus ,Triodontus ,Madagascar ,Biology (General) ,QH301-705.5 - Abstract
New locality records for Madecorphnus niger Frolov, 2010, M. falcatus Paulian, 1992, M. simplex Frolov, 2010, and Triodontus itremoi Paulian, 1977, are given. Endophallus armature of M. niger Frolov, 2010, is described and illustrated.
- Published
- 2013
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8. Stenosternus Karsch, a possible link between Neotropical and Afrotropical Orphninae (Coleoptera, Scarabaeidae)
- Author
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Andrey Frolov
- Subjects
Zoology ,QL1-991 - Abstract
The monotypical orphnine genus Stenosternus Karsch is known from a single specimen of S. costatus collected on the São Tomé island (Gulf of Guinea). The holotype of S. costatus Karsch is re-examined and its characters are discussed and illustrated. Although the genus was implicitly placed by Paulian (1984) in the Old World tribe Orphnini Erichson, re-examination of the holotype of S. costatus shows that it has characters similar to those of the members of the New World tribe Aegidiini Paulian. Placement of Stenosternus in the Aegidiini is supported by the metepisternum widened posteriorly (forming posterior metepisternal lock for closed elytra) and a keel separating basal and anterolateral parts of propleurae. Relationships of Stenosternus with other orphnine taxa and possible ways of origin of São Toméan orphnine fauna are discussed.
- Published
- 2013
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9. A contribution to the study of the Lower Volga center of scarab beetle diversity in Russia: checklist of the tribe Aphodiini (Coleoptera, Scarabaeidae) of Dosang environs
- Author
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Andrey Frolov and Lilia Akhmetova
- Subjects
Scarab beetles ,dung-beetles ,aphodiines ,Caspian lowland desert ,faunistic composition ,Biology (General) ,QH301-705.5 - Abstract
The field sampling of the Aphodiini scarab beetles in Dosang environs (Astrakhan Province, European Russia) in 2006–2012 resulted in the collection of 44 species. All but one of them belong to Aphodius Hellwig (sensu lato). This is apparently the richest recorded local Aphodiini fauna in Russia. The high Aphodiini diversity in the area can be explained by the long vegetative season with high effective heat sum, large livestock providing abundant food resources throughout the year, and location in the transition belt between Volga-Akhtuba Floodplain and Desert floristic districts. The core fauna consists of mesophilous species widely distributed in the Palearctic region and confined to the intrazonal habitats. Other species have ranges mostly limited to the steppe, semidesert, and desert zones.
- Published
- 2013
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10. Cellular uptake and intracellular trafficking of long chain fatty acids
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Mark J. McArthur, Barbara P. Atshaves, Andrey Frolov, William D. Foxworth, Ann B. Kier, and Friedhelm Schroeder
- Subjects
fatty acid ,uptake ,plasma membrane ,binding protein ,trafficking ,fluorescence ,Biochemistry ,QD415-436 - Abstract
While aspects of cellular fatty acid uptake have been studied as early as 50 years ago, recent developments in this rapidly evolving field have yielded new functional insights on the individual mechanistic steps in this process. The extremely low aqueous solubility of long chain fatty acids (LCFA) together with the very high affinity of serum albumin and cytoplasmic fatty acid binding proteins for LCFA have challenged the limits of technology in resolving the individual steps of this process. To date no single mechanism alone accounts for regulation of cellular LCFA uptake. Key regulatory points in cellular uptake of LCFA include: the aqueous solubility of the LCFA; the driving force(s) for LCFA entry into the cell membrane; the relative roles of diffusional and protein mediated LCFA translocation across the plasma membrane; cytoplasmic LCFA binding protein-mediated uptake and/or intracellular diffusion; the activity of LCFA-CoA synthetase; and cytoplasmic protein mediated targeting of LCFA or LCFA-CoAs toward specific metabolic pathways. The emerging picture is that the cell has multiple, overlapping mechanisms that assure adequate uptake and directed intracellular movement of LCFA required for maintenance of physiological functions. The upcoming challenge is to take advantage of new advances in this field to elucidate the differential interactions between these pathways in intact cells and in tissues.—McArthur, M. J., B. P. Atshaves, A. Frolov, W. D. Foxworth, A. B. Kier, and F. Schroeder. Cellular uptake and intracellular trafficking of long chain fatty acids. J. Lipid Res. 1999. 40: 1371–1383.
- Published
- 1999
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11. Alteration of Differentiation Potentials by Modulating GATA Transcription Factors in Murine Embryonic Stem Cells
- Author
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Callinice D. Capo-chichi, Jennifer L. Smedberg, Malgorzata Rula, Emmanuelle Nicolas, Anthony T. Yeung, Richard F. Adamo, Andrey Frolov, Andrew K. Godwin, and Xiang-Xi Xu
- Subjects
Internal medicine ,RC31-1245 - Abstract
Background. Mouse embryonic stem (ES) cells can be differentiated in vitro by aggregation and/or retinoic acid (RA) treatment. The principal differentiation lineage in vitro is extraembryonic primitive endoderm. Dab2, Laminin, GATA4, GATA5, and GATA6 are expressed in embryonic primitive endoderm and play critical roles in its lineage commitment. Results. We found that in the absence of GATA4 or GATA5, RA-induced primitive endoderm differentiation of ES cells was reduced. GATA4 (−/−) ES cells express higher level of GATA5, GATA6, and hepatocyte nuclear factor 4 alpha marker of visceral endoderm lineage. GATA5 (−/−) ES cells express higher level of alpha fetoprotein marker of early liver development. GATA6 (−/−) ES cells express higher level of GATA5 as well as mesoderm and cardiomyocyte markers which are collagen III alpha-1 and tropomyosin1 alpha. Thus, deletion of GATA6 precluded endoderm differentiation but promoted mesoderm lineages. Conclusions. GATA4, GATA5, and GATA6 each convey a unique gene expression pattern and influences ES cell differentiation. We showed that ES cells can be directed to avoid differentiating into primitive endoderm and to adopt unique lineages in vitro by modulating GATA factors. The finding offers a potential approach to produce desirable cell types from ES cells, useful for regenerative cell therapy.
- Published
- 2010
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12. Monitoring of the diamondback moth (Plutella xylostella L.) on the Brassica oleracea L. collection in the vicinity of St. Petersburg
- Author
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Julia Zakharova, Andrey Frolov, and Anna Artemyeva
- Subjects
Physiology ,Genetics ,Plant Science ,Molecular Biology ,Biochemistry ,Ecology, Evolution, Behavior and Systematics ,Biotechnology - Abstract
Background. Diamondback moth (Plutella xylostella L.) has now acquired the status of the most dangerous pest of plants from the Brassicaceae family in the world, including Russia. In order to identify genotypes resistant to the pest, cabbage accessions from the VIR global collection were assessed in the field according to plant infestation and damage by diamondback moth in the vicinity of St. Petersburg.Materials and methods. The infestation of plants by diamondback moth was assessed on model accessions when examining all plants in the plot by (1) the number of larvae and pupae, and (2) leaf damage, assessed using a standard scoring scale. The number of adults was monitored using sticky Delta traps of two designs: (1) cardboard traps equipped with commercial dispensers with synthetic sex pheromone, and (2) plastic LED traps designed at VIZR.Results. The results of field surveys attested to very high variation among cabbage accessions in the rates of infestation and damage to plants caused by diamondback moth. The data on the abundance of adults caught by pheromone traps correlated well with the estimates of larval and pupal density of the pest on plants. The capture rate of diamondback moths with LED traps varied greatly during the season. In June/early July, i.e., during the period of the so called “white” nights, LED traps caught diamondback moths much worse than pheromone ones, but during the second half of July and August their capture rate significantly exceeded that of pheromone traps. As a result, the relationship between numbers of diamondback moth larvae on plants and adults in LED traps turned out to be negative. Conclusion. The resulting materials indicate obvious prospects of studying the VIR global collection in order to identify sources of host plant resistance to diamondback moth. The abundance of this pest in northern regions of its spreading is recommended to be controlled with pheromone traps.
- Published
- 2022
13. Monocotyledon‐like Leaves from the Middle Jurassic of East Siberia (Russia)
- Author
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Andrey FROLOV and Ilya ENUSHCHENKO
- Subjects
Geology - Published
- 2022
14. THE SIMPLEST LOW LINEAR ORDER WITH NO COMPUTABLE COPIES
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ANDREY FROLOV and MAXIM ZUBKOV
- Subjects
Philosophy ,Logic - Abstract
A low linear order with no computable copy constructed by C. Jockusch and R. Soare has Hausdorff rank equal to $2$ . In this regard, the question arises, how simple can be a low linear order with no computable copy from the point of view of the linear order type? The main result of this work is an example of a low strong $\eta $ -representation with no computable copy that is the simplest possible example.
- Published
- 2022
15. On Categoricity of Scattered Linear Orders Of constructive Ranks
- Author
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Andrey Frolov and Maxim Zubkov
- Abstract
In this article we investigated the complexity of isomorphisms be-tween scattered linear orders of constructive ranks. We gave the general upperbound and proved that this bound is sharp. Also, we constructed examples show-ing that the categoricity level of a given scattered linear order can be an arbitraryordinal from 3 to the upper bound, except for the case when the ordinal is thesuccessor of a limit ordinal. The existence question of the scattered linear orderswhose categoricity level equals to the successor of a limit ordinal is still open.
- Published
- 2023
16. Mixed Cerebrovascular and Alzheimer’s Type Pathology Mimicking Lewy Body Disease and Its Possible Contribution to Cognitive Impairment in Elderly Patients with Bipolar Disorder/Schizophrenia
- Author
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Andrey Frolov, Lokesh Coomar, Miguel A. Guzman, and John R. Martin III
- Subjects
General Medicine - Published
- 2022
17. Strategies and tactics of life space exploitation by the European corn borer, Ostrinia nubilalis (Hbn.) (Lepidoptera: Crambidae)
- Author
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Andrey Frolov
- Published
- 2022
18. Review of the Genus Orphnus Macleay, 1819 (Coleoptera: Scarabaeidae: Orphninae) from Kenya, with Description of New Species
- Author
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Andrey Frolov and Lilia Akhmetova
- Subjects
Ecology ,Ecological Modeling ,scarab beetles ,scarabs ,orphnines ,Kenya ,East Africa ,new species ,Agricultural and Biological Sciences (miscellaneous) ,Nature and Landscape Conservation - Abstract
The Kenyan fauna of the scarab beetle subfamily Orphninae is reviewed for the first time based on representative material. Twelve species of the genus Orphnus MacLeay are recorded from the country, including two that are new to science: O. kenyensis Akhmetova et Frolov, sp. nov. and O. tanaensis Akhmetova et Frolov, sp. nov. Lectotypes are designated for O. rufithorax Benderitter, O. mombasaensis Benderitter, and O. jeanneli Benderitter. Keys, diagnoses, illustrations of habitus and male genitalia, and distributional record maps are given.
- Published
- 2022
- Full Text
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19. Mixed Cerebrovascular And Alzheimer’s Type Pathology Mimicking Lewy Body Disease And Its Possible Contribution To the Increased Risk of Developing Cognitive Impairment In Elderly Patients with Bipolar Disorder/Schizophrenia
- Author
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Lokesh Coomar, Andrey Frolov, Miguel Guzman, and John R. Martin
- Subjects
Genetics ,Molecular Biology ,Biochemistry ,Biotechnology - Published
- 2022
20. Cerebral Vascular Density and Its Possible Correlation with Alzheimer Disease Progression in Elderly Individuals with Rheumatoid Arthritis
- Author
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Maurice Nigel A. Maglasang, Andrey Frolov, Miguel Guzman, Scott Echols, and Daniel Daly
- Subjects
Genetics ,Molecular Biology ,Biochemistry ,Biotechnology - Published
- 2022
21. ROLE OF METEOROLOGICAL FACTOR IN LONG-TERM POPULATION DYNAMICS OF THE EUROPEAN CORN BORER, Ostrinia nubilalis Hbn., IN KRASNODAR AREA: THE ANALYSIS OF LIFE TABLES
- Author
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Inna Grushevaya and Andrey Frolov
- Subjects
education.field_of_study ,European corn borer ,Agronomy ,biology ,Population ,General Agricultural and Biological Sciences ,education ,biology.organism_classification ,Term (time) ,Ostrinia - Published
- 2020
22. A Rare Case of 83-Year-Old Transgender Female: Can Thyroid Hormone Deficiency Be Involved in Transgenderism and Gender Dysphoria?
- Author
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Andrey Frolov, Lauren Polcaro, John R. Martin, Craig Lawson, and Yun Tan
- Subjects
Gender dysphoria ,endocrine system ,biology ,Penectomy ,business.industry ,Thyroid ,Physiology ,General Medicine ,medicine.disease ,medicine.anatomical_structure ,Thyroid peroxidase ,Scrotum ,medicine ,biology.protein ,business ,Penis ,Exome sequencing ,Hormone - Abstract
In the current report, we describe an 83-year-old biological male who self- identified as a female by legally changing his first and middle names to female ones and whose death certificate states his sex as a female. The medical history of this individual indicated complete penectomy without further specification. Postmortem physical examination revealed an absence of penis with a large scrotum, transposed urethral orifice, and small testes. The histological analysis of the testes identified abnormal epithelium in the seminiferous tubules that lacked germ and Sertoli cells as well as the interstitium without Leydig cells present. The exome sequencing of the individual’s DNA using the Next Generation Sequencing (NGS) Illumina platform revealed no genetic variants associated with either penile or urethral cancer that could have explained the complete penectomy, but pointed toward a potentially impaired production of T3 and T4 thyroid hormones which could account for the observed testicular malformation. Overall, the data obtained raise an important question as to whether the thyroid hormone axis could be an important part of the hormonal architecture supporting male sexual behavior.
- Published
- 2020
23. A Rare Case of Delayed‐Onset Post‐Stroke Dementia Associated with Cerebral Small Vessel and Alzheimer's Disease Pathologies
- Author
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Andrey Frolov, John R. Martin, Dane Meyer, and Miguel Guzman
- Subjects
medicine.medical_specialty ,business.industry ,Post stroke dementia ,Delayed onset ,Disease ,Biochemistry ,Internal medicine ,Rare case ,Genetics ,medicine ,Cardiology ,Small vessel ,business ,Molecular Biology ,Biotechnology - Published
- 2021
24. The first results of the implementation of the National Project «Health care» in the Lipetsk region
- Author
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Andrey Frolov
- Subjects
Nursing ,business.industry ,Political science ,Health care ,business - Abstract
The article describes the organization of the system of providing medical care to the population of the Lipetsk region according to the main sections of the National project «Health care». The main reasons for the failure to achieve the results of the projects "Cardiovascular diseases", "Oncology", "Primary health care", "Providing medical care for children" and, as a consequence, influence on the demographic indicators of the Lipetsk region are given.
- Published
- 2019
25. Somatosensory behavioral alterations in a NGF-induced persistent low back pain model
- Author
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Nicholas R. Reed, Andrey Frolov, Madison L. Richey, Michael K. Syrett, Joshua W. Little, and William R. Reed
- Subjects
Male ,medicine.medical_specialty ,Stimulation ,Sensory system ,Somatosensory system ,Rats, Sprague-Dawley ,Behavioral Neuroscience ,Internal medicine ,Nerve Growth Factor ,Medicine ,Animals ,biology ,Behavior, Animal ,business.industry ,Low back pain ,Trunk ,Rats ,Disease Models, Animal ,Endocrinology ,Nerve growth factor ,Hyperalgesia ,biology.protein ,Female ,medicine.symptom ,business ,Low Back Pain ,Neurotrophin - Abstract
Low back pain (LBP) is a major global burden in part due to the underlying pathophysiological mechanisms being poorly understood. A LBP rat model involving two injections of nerve growth factor (NGF, an endogenous pain-related neurotrophin) into trunk musculature was recently developed. Additional behavioral work in this NGF-LBP rat model is required to better characterize local and remote somatosensory alterations related to NGF-induced peripheral and central sensitization. This work characterizes the time-dependent development of hypersensitivity to trunk and hindpaw cutaneous mechanical stimulation and deep muscle mechanical hyperalgesia in adult male Sprague-Dawley rats (n = 6/group). Behavioral assays were performed at baseline (Day 0, D0), D2, D5 (pre- and 4 h post-2nd NGF or control injection), D7, D10, and D14 in NGF and control groups. Trunk and hindpaw cutaneous mechanical hypersensitivity were tested using von Frey filaments. Deep trunk mechanical hyperalgesia was determined using a small animal algometer. NGF rats demonstrated increased cutaneous sensitivity to ipsilateral trunk mechanical stimuli at D7, D10, and D14. NGF rats also demonstrated ipsilateral deep mechanical hyperalgesia on D2, D5 + 4 h, D7, D10, and D14. Cutaneous hypersensitivity was delayed compared to deep hyperalgesia in NGF rats. No additional sensory changes were noted. Together, these results indicate that male mechanical somatosensory changes develop primarily locally in the ipsilateral trunk following unilateral NGF injections. These findings contrast with a previous report in female rats using this NGF-LBP model showing more widespread (bilateral) hyperalgesia and remote mechanical hypersensitivity. Future studies will examine potential sex-related pain behavioral differences in the NGF model.
- Published
- 2021
26. Unraveling the Allosteric Cross-Talk Between Coactivator Peptide and Ligand Binding Site in Glucocorticoid Receptor
- Author
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Giuseppina La Sala, Anders Gunnarsson, karl edman, Christian Tyrchan, anders hogner, and Andrey Frolov
- Abstract
Glucocorticoid receptor (GR) is a nuclear receptor that controls critical biological processes by regulating thetranscription of specific genes. There is a known allosteric cross-talk between the ligand and coregulator bindingsites within the GR ligand binding domain that is crucial for the control of the functional response. However, themolecular mechanisms underlying such an allosteric control remain elusive. Here, molecular dynamics (MD)simulations, bioinformatic analysis and biophysical measurements are integrated to capture the structural anddynamic features of the allosteric cross-talk within GR. We identified a network of evolutionarily conservedresidues that enables the allosteric signal transduction, in agreement with experimental data. MD simulationsclarify how such network is dynamically interconnected and offer a mechanistic explanation of how the differentpeptides affect the intensity of the allosteric signal. This study provides useful insights to elucidate the GRallosteric regulation, ultimately, posing the foundation for designing novel drugs.
- Published
- 2021
27. Sagittal Craniosynostosis with Uncommon Anatomical Pathologies in a 56-Year-Old Male Cadaver
- Author
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Joshua Olatunde, Andrey Frolov, James T. Goodrich, John R. Martin, and Craig Lawson
- Subjects
0301 basic medicine ,Fibrous joint ,Pathology ,medicine.medical_specialty ,Torus palatinus ,business.industry ,medicine.medical_treatment ,Case Report ,General Medicine ,medicine.disease ,Sagittal plane ,03 medical and health sciences ,Skull ,Sagittal suture ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Cadaver ,medicine ,lcsh:Pathology ,business ,030217 neurology & neurosurgery ,Exome sequencing ,Craniotomy ,lcsh:RB1-214 - Abstract
Sagittal craniosynostosis (CS) is a pathologic condition that results in premature fusion of the sagittal suture, restricting the transverse growth of the skull leading in some cases to elevated intracranial pressure and neurodevelopmental delay. There is still much to be learned about the etiology of CS. Here, we report a case of 56-year-old male cadaver that we describe as sagittal CS with torus palatinus being an additional anomaly. The craniotomy was unsuccessful (cephalic index, CI = 56) and resulted in abnormal vertical outgrowth of the craniotomized bone strip. The histological analysis of the latter revealed atypical, noncompensatory massive bone overproduction. Exome sequencing of DNA extracted from the cadaveric tissue specimen performed on the Next Generation Sequencing (NGS) platform yielded 81 genetic variants identified as pathologic. Nine of those variants could be directly linked to CS with five of them targeting RhoA GTPase signaling, with a potential to make it sustained in nature. The latter could trigger upregulated calvarial osteogenesis leading to premature suture fusion, skull bone thickening, and craniotomized bone strip outgrowth observed in the present case.
- Published
- 2019
28. A Rare Case of an 83‐Year‐Old Male Transgender: An Anatomical and Genetic Study
- Author
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John R. Martin, Yun Tan, Craig Lawson, Lauren Polcaro, Andrey Frolov, and MariaTeresa A. Tersigni-Tarrant
- Subjects
Pediatrics ,medicine.medical_specialty ,business.industry ,Transgender ,Rare case ,Genetics ,medicine ,business ,Molecular Biology ,Biochemistry ,Biotechnology - Published
- 2019
29. The Branching Pattern and Internal Topography of the Musculocutaneous Nerve
- Author
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Yehia Elgammal, Andrey Frolov, and John R. Martin
- Subjects
Branching (linguistics) ,Genetics ,Anatomy ,Biology ,Molecular Biology ,Biochemistry ,Musculocutaneous nerve ,Biotechnology - Published
- 2020
30. A Rare Case of Human Diphallia Associated with Hypospadias
- Author
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John R. Martin, Yun Tan, Andrey Frolov, and M. W. Rana
- Subjects
0301 basic medicine ,business.industry ,Genitourinary system ,Case Report ,General Medicine ,Diphallia ,medicine.disease ,Bioinformatics ,lcsh:Diseases of the genitourinary system. Urology ,lcsh:RC870-923 ,03 medical and health sciences ,Dissection ,030104 developmental biology ,0302 clinical medicine ,Bifid penis ,Hypospadias ,030220 oncology & carcinogenesis ,Rare case ,Gene duplication ,Etiology ,Medicine ,business - Abstract
Diphallia or penile duplication is a rare congenital variant with an estimated frequency of 1 per 5 to 6 million live births. The extent of duplication varies widely and typically occurs with other malformations including urogenital, gastrointestinal, and musculoskeletal anomalies. Here we present a case of human diphallia that was detected during routine dissection of an 84-year-old cadaver. Upon thorough examination, this case was characterized as a complete bifid penis which was accompanied by hypospadias with no other anatomical abnormalities detected. To gain insights into the etiology of this case, we analyzed DNA procured from the body for putative genetic variants using Next Generation Sequencing (NGS) technology. Our results support clinical observations consistent with human diphallia being a polygenic syndrome and identify new genetic variants that might underlie its etiology.
- Published
- 2018
31. Situs Inversus Totalis in a 96‐Year‐Old Female Cadaver: Genetic Insights
- Author
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Andrey Frolov, Daniel T. Daly, Mia Jenkins, Yun Tan, John R. Martin, and Craig Lawson
- Subjects
Situs inversus ,business.industry ,Cadaver ,Genetics ,Medicine ,Anatomy ,business ,medicine.disease ,Molecular Biology ,Biochemistry ,Biotechnology - Published
- 2018
32. Sagittal Craniosynostosis and Related Cranial Anomalies: Genetic Insights
- Author
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Andrey Frolov, John R. Martin, Josh Olatunde, and MariaTeresa A. Tersigni-Tarrant
- Subjects
business.industry ,Genetics ,Sagittal craniosynostosis ,Medicine ,Anatomy ,business ,Molecular Biology ,Biochemistry ,Biotechnology - Published
- 2018
33. Lumbar Spinal Cord Astrocytic Hyperactivation is Associated with Thrombospondin‐4 Upregulation during Persistent Low Back Pain
- Author
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Michael K. Syrett, William R. Reed, Joshua W. Little, Andrey Frolov, Nicholas R. Reed, and Madison L. Richey
- Subjects
Pathology ,medicine.medical_specialty ,education.field_of_study ,Hyperactivation ,business.industry ,Biochemistry ,Low back pain ,Lumbar Spinal Cord ,Downregulation and upregulation ,Thrombospondin 4 ,Genetics ,medicine ,medicine.symptom ,business ,education ,Molecular Biology ,Biotechnology - Published
- 2018
34. Time‐dependent lumbar spinal cord astrocytic hyperactivation occurs in the deep dorsal horn during the maintenance of nerve growth factor‐induced low back pain
- Author
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William R. Reed, Andrey Frolov, Joshua W. Little, Nicholas R. Reed, Vruta Kansara, and Madison L. Richey
- Subjects
Dorsum ,Hyperactivation ,French horn ,business.industry ,Anatomy ,Biochemistry ,Low back pain ,Lumbar Spinal Cord ,Nerve growth factor ,Genetics ,medicine ,medicine.symptom ,business ,Molecular Biology ,Biotechnology - Published
- 2018
35. The evolution of federative system of Russia and constitutional-legal fundamentals of Russian federalism
- Author
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Andrey Frolov
- Abstract
The present article is devolved to the analysis of evolution of federative relationships in Russia between 1990 and 2017 in the context of this process correlation with development of the system of Russian law. The study is based on the search of logic for permanent changes of nature of relationships between center and region, searching for cause-effect relationships of behavior of federal authorities in the bifurcation points. The author distinguishes stages of this process and the features inherent in each stage, analyses historical events and conditions that directly led to the emergence of certain political and law phenomena. The research highlights that the Constitution of Russian Federation is currently unavailable to practically limit the balance between the center and regions; it is showing the main contradictions in the Constitution that directly confirm the ability of the federal center to shift that balance when it's convenient to it, and the ways to resolve these contradictions; the possible consequences of disregarding the necessity to the Constitution to be modified accordingly, are being analyzed.
- Published
- 2017
36. Reduced T Cell–Dependent Humoral Immune Response in Microsomal Prostaglandin E Synthase-1 Null Mice Is Mediated by Nonhematopoietic Cells
- Author
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Rahul Matnani, Andrey Frolov, Jerold G. Woodward, Fumiaki Kojima, and Leslie J. Crofford
- Subjects
Male ,musculoskeletal diseases ,Interleukin 2 ,medicine.medical_specialty ,T-Lymphocytes ,T cell ,Immunology ,chemical and pharmacologic phenomena ,Article ,Immunoglobulin G ,Interferon-gamma ,Mice ,Immune system ,Internal medicine ,medicine ,Animals ,Immunology and Allergy ,Cells, Cultured ,Interleukin 4 ,Bone Marrow Transplantation ,Prostaglandin-E Synthases ,Mice, Knockout ,biology ,Interleukin-17 ,Autoantibody ,Germinal center ,Arthritis, Experimental ,Immunity, Humoral ,Intramolecular Oxidoreductases ,Endocrinology ,medicine.anatomical_structure ,Immunoglobulin M ,Mice, Inbred DBA ,biology.protein ,Interleukin-2 ,Female ,lipids (amino acids, peptides, and proteins) ,Collagen ,Interleukin-4 ,Interleukin 17 ,medicine.drug - Abstract
Microsomal PGE synthase-1 (mPGES-1) is an inducible enzyme that specifically catalyzes the conversion of PGH2 to PGE2. We showed that mPGES-1 null mice had a significantly reduced incidence and severity of collagen-induced arthritis compared with wild-type (WT) mice associated with a marked reduction in Abs to type II collagen. In this study, we further elucidated the role of mPGES-1 in the humoral immune response. Basal levels of serum IgM and IgG were significantly reduced in mPGES-1 null mice. Compared with WT mice, mPGES-1 null mice exhibited a significant reduction of hapten-specific serum Abs in response to immunization with the T cell–dependent (TD) Ag DNP-keyhole limpet hemocyanin. Immunization with the T cell–independent type 1 Ag trinitrophenyl-LPS or the T cell–independent type 2 Ag DNP-Ficoll revealed minimal differences between strains. Germinal center formation in the spleen of mPGES-1 null and WT mice were similar after immunization with DNP-keyhole limpet hemocyanin. To determine whether the effect of mPGES-1 and PGE2 was localized to hematopoietic or nonhematopoietic cells, we generated bone marrow chimeras. We demonstrated that mPGES-1 deficiency in nonhematopoietic cells was the critical factor for reduced TD Ab production. We conclude that mPGES-1 and PGE2-dependent phenotypic changes of nonhematopoietic/mesenchymal stromal cells play a key role in TD humoral immune responses in vivo. These findings may have relevance to the pathogenesis of rheumatoid arthritis and other autoimmune inflammatory diseases associated with autoantibody formation.
- Published
- 2013
37. Niemann-Pick Type C2 Deficiency in Human Fibroblasts Confers Robust and Selective Activation of Prostaglandin E2 Biosynthesis
- Author
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Erik C. Cook, Andrey Frolov, Bruce D. Hammock, Hua Dong, Min Jiang, Leslie J. Crofford, Lihua Yang, and Rahul Matnani
- Subjects
congenital, hereditary, and neonatal diseases and abnormalities ,Interleukin-1beta ,Intracellular Space ,Vesicular Transport Proteins ,Regulator ,Inflammation ,Biology ,Biochemistry ,Dinoprostone ,Proinflammatory cytokine ,Arthritis, Rheumatoid ,Downregulation and upregulation ,hemic and lymphatic diseases ,medicine ,Metabolome ,Humans ,Prostaglandin E2 ,Fibroblast ,Molecular Biology ,Glycoproteins ,Oligonucleotide Array Sequence Analysis ,Microscopy, Confocal ,Group IV Phospholipases A2 ,Synovial Membrane ,nutritional and metabolic diseases ,Cell Biology ,Fibroblasts ,Molecular biology ,Biosynthetic Pathways ,Up-Regulation ,Cell biology ,Protein Transport ,medicine.anatomical_structure ,Inflammation Mediators ,medicine.symptom ,Signal transduction ,Carrier Proteins ,Chromatography, Liquid ,Signal Transduction ,medicine.drug - Abstract
Activated fibroblasts, also known as myofibroblasts, are mediators of several major human pathologies including proliferative fibrotic disorders, invasive tumor growth, rheumatoid arthritis, and atherosclerosis. We previously identified Niemann-Pick type C2 (NPC2) protein as a negative regulator of fibroblast activation (Csepeggi, C., Jiang, M., Kojima, F., Crofford, L. J., and Frolov, A. (2011) J. Biol. Chem. 286, 2078–2087). Here we report that NPC2-deficiency leads to a dramatic up-regulation of the arachidonic acid (AA) metabolic pathway in human fibroblasts. The major enzymes in this pathway, cPLA2 type IVA, COX-2, and mPGES-1, were dramatically up-regulated at both the transcriptional and translational levels. The specific phenotypic changes resulted in a >10-fold increase in the production and secretion of a key modulator of inflammation and immunity, prostaglandin E2. More importantly, AA metabolome profiling by liquid chromatography/tandem mass-spectrometry revealed the very specific nature of prostaglandin E2 up-regulation as the other analyzed AA metabolites derived from the COX-2, cytochrome P450, 5/15-lipoxygenase, and non-enzymatic oxidative pathways were mostly down-regulated. Blocking activity of cPLA2 efficiently suppressed expression of inflammatory cytokines, IL-1β and IL-6, thereby identifying cPLA2 as an important regulator of the inflammatory program in NPC2-null cells. Altogether, these studies highlight NPC2 as a specific regulator of AA metabolism and inflammation that suggests potential for NPC2 protein or its related signaling in the treatment of inflammatory diseases characterized by the presence of activated fibroblasts. Background: NPC2 is a protein that negatively regulates fibroblast activation. Results: NPC2-null human fibroblasts display induction of cPLA2, COX-2, and mPGES-1 expression that may contribute to the observed robust and selective activation of PGE2 biosynthesis. Conclusion: NPC2 may regulate the activated fibroblast inflammatory program through modulation of a cPLA2-dependent biosynthetic pathway. Significance: NPC2 may represent a novel therapeutic tool for the treatment of inflammatory diseases.
- Published
- 2013
38. A new brachypterous scarab species, Orphnus longicornis (Coleoptera: Scarabaeidae: Orphninae), from the East African Rift
- Author
-
Andrey, Frolov and Lilia, Akhmetova
- Subjects
Coleoptera ,Male ,Germany ,Museums ,Animal Structures ,Animals ,Body Size ,Organ Size ,Animal Distribution - Abstract
The Afrotropical Region is the center of the diversity of the scarab beetle genus Orphnus MacLeay, 1819 (Coleoptera: Scarabaeidae: Orphninae), with 94 species occurring from Sahel in the north to Little Karoo in the south (Paulian, 1948; Petrovitz, 1971; Frolov, 2008). The East African Rift is one of the richest regions of the Afrotropics housing more than 20 species of Orphnus (Paulian, 1948; Frolov, 2013), most of which are endemic to this region. Yet the scarab beetle fauna of the East African Rift, and especially the Eastern Arc Mountains, is still inadequately studied. Examination of the material housed in the Museum of Natural History of Humboldt-Universität, Berlin, Germany (ZMHUB), revealed a series of brachypterous Orphnus beetles belonging to an undescribed species. The new species is described and illustrated below.
- Published
- 2015
39. A microRNA gene expression signature predicts response to erlotinib in epithelial cancer cell lines and targets EMT
- Author
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M Willian, Joel S. Britson, R Timmons, Justin M. Balko, J L Bryant, Esther P. Black, and Andrey Frolov
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,Epithelial-Mesenchymal Transition ,MicroRNA Gene ,Antineoplastic Agents ,Biology ,Erlotinib Hydrochloride ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,microRNA ,medicine ,Humans ,metastasis ,Neoplasms, Glandular and Epithelial ,Epithelial–mesenchymal transition ,Epidermal growth factor receptor ,Molecular Diagnostics ,030304 developmental biology ,EGFR inhibitors ,0303 health sciences ,Gene Expression Profiling ,targeted therapy ,invasion ,respiratory tract diseases ,3. Good health ,ErbB Receptors ,Gene expression profiling ,MicroRNAs ,Oncology ,030220 oncology & carcinogenesis ,Quinazolines ,Cancer research ,biology.protein ,biomarker ,Ectopic expression ,Erlotinib ,medicine.drug - Abstract
Background: Treatment with epidermal growth factor receptor (EGFR) inhibitors can result in clinical response in non-small-cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) for some unselected patients. EGFR and KRAS mutation status, amplification of EGFR, or gene expression predictors of response can forecast sensitivity to EGFR inhibition. Methods: Using an NSCLC cell line model system, we identified and characterised microRNA (miRNA) gene expression that predicts response to EGFR inhibition. Results: Expression of 13 miRNA genes predicts response to EGFR inhibition in cancer cell lines and tumours, and discriminates primary from metastatic tumours. Signature genes target proteins that are enriched for epithelial-to-mesenchymal transition (EMT) genes. Epithelial-to-mesenchymal transition predicts EGFR inhibitor resistance and metastatic behaviour. The EMT transcription factor, ZEB1, shows altered expression in erlotinib-sensitive NSCLC and PDAC, where many signature miRNA genes are upregulated. Ectopic expression of mir-200c alters expression of EMT proteins, sensitivity to erlotinib, and migration in lung cells. Treatment with TGFβ1 changes expression of signature miRNA and EMT proteins and modulates migration in lung cells. Conclusion: From these data, we hypothesise that the tumour microenvironment elicits TGFβ1 and stimulates a miRNA gene expression program that induces resistance to anti-EGFR therapy and drives lung tumour cells to EMT, invasion, and metastasis.
- Published
- 2011
40. Targeting ErbB3-mediated stromal–epithelial interactions in pancreatic ductal adenocarcinoma
- Author
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Peter Kulesza, Andra R. Frost, Andrew V. Kossenkov, Martin J. Heslin, Alevtina Mikhaylina, Juan Pablo Arnoletti, J.S. Liles, and Andrey Frolov
- Subjects
Cancer Research ,Stromal cell ,Receptor, ErbB-3 ,EGFR ,Neuregulin-1 ,pancreatic cancer ,Blotting, Western ,Transplantation, Heterologous ,ErbB3 antibody ,Antineoplastic Agents ,Cell Communication ,Mice, SCID ,Biology ,Erlotinib Hydrochloride ,Mice ,ErbB3 ,Pancreatic cancer ,medicine ,Animals ,Humans ,ERBB3 ,Epidermal growth factor receptor ,Neuregulin 1 ,Phosphorylation ,Cell Proliferation ,Reverse Transcriptase Polymerase Chain Reaction ,Fibroblasts ,medicine.disease ,Immunohistochemistry ,Transplantation ,ErbB Receptors ,Pancreatic Neoplasms ,Disease Models, Animal ,Oncology ,tumourigenesis ,Cancer research ,biology.protein ,Quinazolines ,Female ,Erlotinib ,Translational Therapeutics ,Proto-Oncogene Proteins c-akt ,medicine.drug ,Carcinoma, Pancreatic Ductal ,Signal Transduction - Abstract
Background: We sought to investigate the role of ErbB3-mediated signalling on the interaction between pancreatic cancer-associated fibroblasts (CAF) and carcinoma cells in an effort to disrupt tumourigenic pancreatic ductal adenocarcinoma (PDAC) stromal–epithelial cross-communication. Methods: Primary CAF cultures were established from human PDAC surgical specimens. AsPC-1 pancreatic cancer cell murine subcutaneous xenografts were developed in the presence and absence of CAF and were subsequently treated with epidermal growth factor receptor (EGFR) inhibitors (erlotinib) and ErbB3 inhibitors (MM-121, monoclonal ErbB3 antibody). Results: Cancer-associated fibroblasts were found to secrete neuregulin-1 (NRG-1), which promoted proliferation via phosphorylation of ErbB3 and AKT in AsPC-1 PDAC cells. This signalling cascade was effectively inhibited both in vitro and in vivo by specific ErbB3 blockade with MM-121, with greater degree of tumourigenesis inhibition when combined with erlotinib. The CAF–AsPC-1 pancreatic cancer xenografts reached significantly greater tumour volume than those xenografts lacking CAF and were resistant to the anti-tumour effects of EGFR inhibition with erlotinib. Conclusion: Cancer-associated fibroblasts-derived NRG-1 promote PDAC tumourigenesis via ErbB3-AKT signalling and overcomes single-agent EGFR inhibition. Disruption of this stromally mediated tumourigenic mechanism is best obtained through combined EGFR-ErbB3 inhibition with both erlotinib and MM-121. We have identified the NRG-1/ErbB3 axis as an attractive molecular target for the interruption of tumourigenic stromal–epithelial interactions within the PDAC microenvironment.
- Published
- 2011
41. THE FUTURE OF RUSSIAN ARMS
- Author
-
Andrey Frolov
- Published
- 2011
42. Somatic Cell Plasticity and Niemann-Pick Type C2 Protein
- Author
-
Fumiaki Kojima, Min Jiang, Chad Csepeggi, Andrey Frolov, and Leslie J. Crofford
- Subjects
MAPK/ERK pathway ,congenital, hereditary, and neonatal diseases and abnormalities ,Mitogen-Activated Protein Kinase 3 ,nutritional and metabolic diseases ,Cell Biology ,Biology ,Biochemistry ,Cell biology ,medicine.anatomical_structure ,Fibroblast activation protein, alpha ,hemic and lymphatic diseases ,Cancer research ,medicine ,Phosphorylation ,Gene silencing ,Signal transduction ,Fibroblast ,Protein kinase A ,Molecular Biology - Abstract
A growing body of evidence points toward activated fibroblasts, also known as myofibroblasts, as one of the leading mediators in several major human pathologies including proliferative fibrotic disorders, invasive tumor growth, rheumatoid arthritis, and atherosclerosis. Niemann-Pick Type C2 (NPC2) protein has been recently identified as a product of the second gene in NPC disease. It encodes ubiquitous, highly conserved, secretory protein with the poorly defined function. Here we show that NPC2 deficiency in human fibroblasts confers their activation. The activation phenomenon was not limited to fibroblasts as it was also observed in aortic smooth muscle cells upon silencing NPC2 gene by siRNA. More importantly, activated synovial fibroblasts isolated from patients with rheumatoid arthritis were also identified as NPC2-deficient at both the NPC2 mRNA and protein levels. The molecular mechanism responsible for activation of NPC2-null cells was shown to be a sustained phosphorylation of ERK 1/2 mitogen-activated protein kinase (MAPK), which fulfills both the sufficient and necessary fibroblast activation criteria. All of these findings highlight a novel mechanism where NPC2 by negatively regulating ERK 1/2 MAPK phosphorylation may efficiently suppress development of maladaptive tissue remodeling and inflammation.
- Published
- 2011
43. Somatic Cell Plasticity and Niemann-Pick Type C2 Protein
- Author
-
Chad Csepeggi, Min Jiang, and Andrey Frolov
- Subjects
medicine.medical_specialty ,Intracrine ,Cellular differentiation ,Mesenchymal stem cell ,nutritional and metabolic diseases ,Cell Biology ,Biology ,Biochemistry ,Cell biology ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Adipogenesis ,Internal medicine ,Adipocyte ,medicine ,Gene silencing ,Progenitor cell ,Autocrine signalling ,Molecular Biology - Abstract
The phenotypic stability of somatic cells is essential for the maintenance of both structural and functional organ integrity of the adult human body. Deregulated cell plasticity could result in the development of debilitating diseases such as cancer, fibrosis, atherosclerosis, obesity, and type 2 diabetes. We have previously demonstrated that a nonsense mutation in the NPC2 gene, which encodes ubiquitous, highly conserved, secretory protein with unknown function, leads to activation of human skin fibroblasts. The activated fibroblasts, also known as myofibroblasts, have the properties of mesenchymal stem cells and are able to differentiate along the mesodermal and endodermal lineages. Here we show that NPC2-null, but not the normal skin fibroblasts, possess characteristics of adipogenic progenitors as demonstrated by their specific gene expression pattern as well as the ability for efficient differentiation into white adipocytes. The presence of NPC2 in mature white adipocytes was also necessary for their maintenance because silencing NPC2 in differentiated cells by siRNA stimulated PPARG expression, which was followed by a shift toward a more favorable, brown adipocyte-like metabolic state characterized by up-regulated lipolysis and increased insulin sensitivity. It appears that NPC2 controls both the adipogenesis and the metabolic state of mature white adipocytes through a common mechanism that is linked to activation of FGFR2 that could be followed by induction of PPARG expression. Altogether, the current study highlights NPC2 as a novel intracrine/autocrine factor that controls adipocyte differentiation and function as well as potential therapeutic target for the treatment of type 2 diabetes and related metabolic disorders.
- Published
- 2010
44. A phase I study evaluating the role of the anti-epidermal growth factor receptor (EGFR) antibody cetuximab as a radiosensitizer with chemoradiation for locally advanced pancreatic cancer
- Author
-
S. Russo, Shyam Varadarajulu, Edward W Greeno, John D. Christein, Nirag Jhala, T. E. Wood, Robert A. Oster, Andrey Frolov, Donald J. Buchsbaum, Selwyn M. Vickers, Kimberly S. Keene, Juan Pablo Arnoletti, M. A. Eloubeidi, and James Posey
- Subjects
Male ,Oncology ,Cancer Research ,medicine.medical_treatment ,Cetuximab ,Toxicology ,Deoxycytidine ,EGFR Antibody ,Cohort Studies ,Antineoplastic Combined Chemotherapy Protocols ,Pharmacology (medical) ,Epidermal growth factor receptor ,Aged, 80 and over ,biology ,Antibodies, Monoclonal ,Middle Aged ,Cadherins ,Combined Modality Therapy ,ErbB Receptors ,Gene Expression Regulation, Neoplastic ,Survival Rate ,medicine.anatomical_structure ,Female ,Pancreas ,medicine.drug ,Adult ,medicine.medical_specialty ,Radiosensitizer ,Epithelial-Mesenchymal Transition ,Biopsy, Fine-Needle ,Antineoplastic Agents ,Adenocarcinoma ,Antibodies, Monoclonal, Humanized ,Article ,Internal medicine ,Pancreatic cancer ,medicine ,Humans ,Vimentin ,Aged ,Pharmacology ,Dose-Response Relationship, Drug ,business.industry ,Gene Expression Profiling ,medicine.disease ,Gemcitabine ,Pancreatic Neoplasms ,Radiation therapy ,biology.protein ,Feasibility Studies ,business - Abstract
(1) To determine the safety of the epidermal growth factor receptor (EGFR) antibody cetuximab with concurrent gemcitabine and abdominal radiation in the treatment of patients with locally advanced adenocarcinoma of the pancreas. (2) To evaluate the feasibility of pancreatic cancer cell epithelial-mesenchymal transition (EMT) molecular profiling as a potential predictor of response to anti-EGFR treatment.Patients with non-metastatic, locally advanced pancreatic cancer were treated in this dose escalation study with gemcitabine (0-300 mg/m(2)/week) given concurrently with cetuximab (400 mg/m(2) loading dose, 250 mg/m(2) weekly maintenance dose) and abdominal irradiation (50.4 Gy). Expression of E-cadherin and vimentin was assessed by immunohistochemistry in diagnostic endoscopic ultrasound fine-needle aspiration (EUS-FNA) specimens.Sixteen patients were enrolled in 4 treatment cohorts with escalating doses of gemcitabine. Incidence of grade 1-2 adverse events was 96%, and incidence of 3-4 adverse events was 9%. There were no treatment-related mortalities. Two patients who exhibited favorable treatment response underwent surgical exploration and were intraoperatively confirmed to have unresectable tumors. Median overall survival was 10.5 months. Pancreatic cancer cell expression of E-cadherin and vimentin was successfully determined in EUS-FNA specimens from 4 patients.Cetuximab can be safely administered with abdominal radiation and concurrent gemcitabine (up to 300 mg/m(2)/week) in patients with locally advanced adenocarcinoma of the pancreas. This combined therapy modality exhibited limited activity. Diagnostic EUS-FNA specimens could be analyzed for molecular markers of EMT in a minority of patients with pancreatic cancer.
- Published
- 2010
45. A review of scarabs of the subgenus Nobius Mulsant et Rey, genus Aphodius Illiger (Coleoptera, Scarabaeidae), of the fauna of Russia and neighboring countries
- Author
-
Andrey Frolov and Lilia Akhmetova
- Subjects
Insect Science - Published
- 2008
46. Epidermal growth factor receptor (EGFR) is highly conserved in pancreatic cancer
- Author
-
Donald J. Buchsbaum, Martin J. Heslin, J. Harrison Howard, Nirag Jhala, Andrey Frolov, Natalya Frolova, J. Pablo Arnoletti, Selwyn M. Vickers, and Ching Wei D. Tzeng
- Subjects
Male ,Pancreatic disease ,DNA Mutational Analysis ,Adenocarcinoma ,Cell Line, Tumor ,Pancreatic cancer ,medicine ,Humans ,Epidermal growth factor receptor ,Lung cancer ,Aged ,Aged, 80 and over ,biology ,business.industry ,Cancer ,Middle Aged ,medicine.disease ,ErbB Receptors ,Pancreatic Neoplasms ,Mutation ,Cancer research ,biology.protein ,Female ,Surgery ,CA19-9 ,Erlotinib ,business ,medicine.drug - Abstract
Background Pancreatic cancer remains a deadly disease, and the vast majority of pancreatic cancer patients are not candidates for treatment with curative intent. Erlotinib, an EGFR-specific tyrosine kinase inhibitor, was approved recently for use in patients with pancreatic cancer. Somatic mutations in the EGFR gene appear to predict survival and response to tyrosine kinase inhibitor therapy in a subset of patients with non–small-cell lung cancer (NSCLC). Methods The purpose of this study was to characterize EGFR mutations in pancreatic adenocarcinoma. EGFR TK mutations were analyzed in 9 pancreatic carcinoma cell lines and 31 clinical specimens from patients with pancreatic cancer who underwent resection. Using laser capture microdissection, tumor cells from patients were harvested selectively for genomic DNA extraction. Mutations were examined by direct sequencing of exons 18-21. Results Of 9 pancreatic cancer cell lines, 6 had either 2454G>A or 2361G>A mutations in exon 20. Of 31 patients, 25 patients had 2361G>A in exon 20, and 1 patient had 2508C>T in exon 21. All were silent mutations. Conclusions The EGFR tyrosine kinase domain is highly conserved in pancreatic cancer. The association among EGFR mutation status, clinical prognosis, and response to anti-EGFR therapy described in NSCLC may not be applicable to pancreatic cancer. This observation does not diminish the possible role of anti-EGFR therapy in pancreatic cancer because there remains a need to explore alternative explanations for pancreatic cancer aberrant EGFR pathway activation such as ligand overexpression, gene amplification, and loss of inhibitory mechanisms.
- Published
- 2007
47. Advanced Data-Driven Performance Analysis For Mature Waterfloods
- Author
-
Egor Ulyanov, Egor Mikhaylenko, Fedor Grishko, Eduard Nizamutdinov, Runo Mijnarends, Andrey Frolov, Oleg Plokhotnichenko, Andrey Valerevich Gladkov, Anton Lvov, Surovets Irina, Yakov Volokitin, Maria Belyanushkina, and Svyatoslav Kryanev
- Subjects
Engineering management ,Engineering ,business.industry ,Management science ,Data management ,business ,Data-driven - Abstract
We present a novel, data-driven approach to integrated well/reservoir performance analysis and opportunity identification for mid- to late-life pattern waterfloods. The Salym group of oilfields is located onshore in Western Siberia, Russia's prime oil producing province, and is operated by Salym Petroleum Development (SPD), a 50-50 joint venture between Shell and Gazprom Neft. The main productive formation, comprising strongly layered, deltaic/fluviatile sandstones, has been developed as a pattern waterflood, with over 950 deviated wells drilled since 2004. Overall watercut is currently around 82% and with oil production declining at 6-7% year on year, waterflood management is an absolute strategic priority. The operator has responded to this challenge by investing heavily in waterflood management and performance evaluation. Particularly, a dedicated effort was made to develop the company's enterprise information architecture and create a purpose-built online waterflood management tool (WMT). All Salym geological, completion, production and well status data is automatically quality-checked, stored and updated in an integrated waterflood database and made accessible through the WMT. The WMT provides a wide range of functionality for data visualization, performance diagnostics and analysis. Furthermore, it is coupled to a full-field surveillance simulation model, which auto-updates with new oilfield data as it becomes available and outputs streamlines, well allocation factors, maps of remaining oil distribution and pattern- and block-level calculated properties. These technologies have enabled the development and implementation of a structured methodology for waterflood performance evaluation that involves systematic assessment of blocks of 20-50 wells in the form of an Annual Field Review (AFR) followed by a series of deep-dive Integrated Block Reviews (IBRs). During the AFR, each block is assessed against a set of KPIs and scored and prioritised in terms of its health status and projected recovery shortfall. Based on this prioritisation, blocks are scheduled for review in an IBR during the course of the year. The IBRs focus on individual wells, patterns and reservoirs and during the reviews concrete well, reservoir and facilities management (WRFM) opportunities are identified to address performance gaps and sweep or accelerate remaining oil. These opportunities are captured in an online opportunity register coupled to an online database for workover strategy preparation. The framework of technologies and processes presented in this paper was instrumental in planning and executing over 260 WRFM activities (not including simple pump change-outs) across the Salym fields in 2014, delivering in excess of 3.2 Mln bbls of in-year oil production.
- Published
- 2015
48. Advanced Data-Driven Performance Analysis For Mature Waterfloods (Russian)
- Author
-
Oleg Plokhotnichenko, Egor Ulyanov, Svyatoslav Kryanev, Anton Lvov, Fedor Grishko, Surovets Irina, Eduard Nizamutdinov, Runo Mijnarends, Egor Mikhaylenko, Yakov Volokitin, Andrey Frolov, Andrey Valerevich Gladkov, and Maria Belyanushkina
- Subjects
Engineering management ,Engineering ,business.industry ,Management science ,Data management ,business ,Data-driven - Published
- 2015
49. A Regulatory Role for 1-Acylglycerol-3-phosphate-O-acyltransferase 2 in Adipocyte Differentiation
- Author
-
Xianlin Han, Li Cao, Perry E. Bickel, Sarah E. Gale, Andrey Frolov, Jean E. Schaffer, Daniel S. Ory, and Anne M. Bowcock
- Subjects
Transcriptional Activation ,Spectrometry, Mass, Electrospray Ionization ,Time Factors ,Lipodystrophy ,Cellular differentiation ,Blotting, Western ,Phospholipid ,CHO Cells ,Biology ,Endoplasmic Reticulum ,Biochemistry ,Mice ,chemistry.chemical_compound ,Cricetinae ,Adipocyte ,Lysophosphatidic acid ,Adipocytes ,Animals ,Humans ,RNA, Messenger ,RNA, Small Interfering ,Molecular Biology ,Phospholipids ,DNA Primers ,Gene knockdown ,Reverse Transcriptase Polymerase Chain Reaction ,Cell Differentiation ,Intracellular Membranes ,Cell Biology ,Phosphatidic acid ,1-Acylglycerol-3-Phosphate O-Acyltransferase ,Lipids ,Metabolic pathway ,Phenotype ,Microscopy, Fluorescence ,chemistry ,Adipogenesis ,RNA ,Electrophoresis, Polyacrylamide Gel ,Acyltransferases - Abstract
Mutations in the 1-acylglycerol-3-phosphate-O-acyltransferase 2 (AGPAT2) gene have been identified in individuals affected with congenital generalized lipodystrophy (CGL). AGPAT2 catalyzes acylation of lysophosphatidic acid to phosphatidic acid, a precursor for both triacylglycerol (TAG) and phospholipid synthesis. Recent studies suggest that reduced AGPAT2 enzymatic activity may underlie the CGL clinical phenotype. To gain insight into how altered AGPAT2 activity causes lipodystrophy, we examined the effect of knockdown of AGPAT2 expression in preadipocytes on TAG synthesis and storage, and on adipocyte differentiation. We show that AGPAT2 mRNA expression is induced 30-fold during adipocyte differentiation and that AGPAT2 enzymatic activity is required for TAG mass accumulation in mature adipocytes. We demonstrate that small interference RNA-mediated knockdown of AGPAT2 expression prevents appropriate early induction of C/EBPbeta and PPARgamma, key transcriptional activators of the adipogenic program, and delays expression of multiple adipocyte-related genes. The unexpected finding, that levels of several phospholipid species, including phosphatidic acid (PA), are elevated in TAG-depleted adipocytes with AGPAT2 knockdown, suggests that impaired AGPAT2 activity affects availability of PA for TAG synthesis but not overall PA synthesis nor utilization of PA for phospholipid synthesis. These findings underscore the importance of an AGPAT2-mediated metabolic pathway in adipocyte differentiation.
- Published
- 2006
50. Tumor-Associated Down-Regulation of 15-Lipoxygenase-1 Is Reversed by Celecoxib in Colorectal Cancer
- Author
-
Courtney M. Townsend, J. Pablo Arnoletti, William M. Boedefeld, Richie Soong, Kirby I. Bland, Andrey Frolov, Ashley Hawkins, Martin J. Heslin, Nipun B. Merchant, Marshall M. Urist, and Dai H. Chung
- Subjects
Adenoma ,Male ,musculoskeletal diseases ,Programmed cell death ,Pathology ,medicine.medical_specialty ,endocrine system diseases ,Colorectal cancer ,Blotting, Western ,Down-Regulation ,Apoptosis ,Tumor Cells, Cultured ,Carcinoma ,Arachidonate 15-Lipoxygenase ,Humans ,Medicine ,Cyclooxygenase Inhibitors ,Sulfonamides ,integumentary system ,business.industry ,food and beverages ,Cancer ,Original Articles ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Gene Expression Regulation, Neoplastic ,Linoleic Acids ,Celecoxib ,Cell culture ,Cancer research ,Eicosanoids ,Pyrazoles ,Female ,lipids (amino acids, peptides, and proteins) ,Surgery ,Colorectal Neoplasms ,business ,medicine.drug - Abstract
Objective: To evaluate the role of celecoxib on 15-lipoxygenase-1 (15-LOX-1) expression, protein levels, and rates of apoptosis in colorectal cancer cell lines. Also, to evaluate the expression of 15-LOX-1 in human normal mucosa, adenoma, and carcinoma with correlation to overall survival. Background Data: The function of 15-LOX-1 is to maintain normal rates of apoptosis (programmed cell death). Decreased apoptosis is one mechanism of cancer growth and dissemination. It is our hypothesis that expression of 15-LOX-1 is reduced in human colorectal cancer (CRC) and the administration of celecoxib can reverse this process and induce apoptosis. Methods: Effect of celecoxib in cell culture: The effect of 40 μmol/L celecoxib was compared with untreated controls in tissue culture utilizing HT-29 and DLD-1 CRC cell lines. Expression of 15-LOX-1 protein was measured by immunoblot. Induction of apoptosis was evaluated by annexin V staining. All data are presented as mean ± SEM, with significance defined as P < 0.05. 15-LOX-1 in human CRC: From February 1998 to January 2002, 126 patients underwent surgical resection of either colorectal adenomas (n = 24) or carcinomas (n = 102), or both (n = 25). Tissue was macrodissected, snap frozen, and stored at -80°C. After tissue processing, RNA was extracted and gene expression of 15-LOX-1 was quantified utilizing ABI prism real-time quantitative RT-PCR. Significance evaluated by the Wilcoxon signed rank test. Results: Effect of celecoxib in cell culture: After 72 hours of treatment with celecoxib, immunoblot demonstrated a 1.5- to 2-fold increase inl5-LOX-1 protein expression in HT-29 and DLD-1 cells, respectively. Celecoxib produced greater than a 2-fold increase in the rate of apoptosis compared with control cells in both cell lines (P < 0.05). 15-LOX-1 in human CRC: The mean age of the patients was 62 ± 1 years; 78% were white and 48% were female. The mean size of the polyps and cancers were 3.0 ± 0.4 and 5.0 ± 0.1 cm, respectively. Expression of 15-LOX-1 relative to S9 was 30 in normal mucosa and significantly down-regulated to 11 in adenomas and 16 in carcinomas (P < 0.05). Conclusions: 15-LOX-1 gene expression is significantly reduced in both human colorectal adenomas and carcinomas and associated with decreased survival. Administration of celecoxib restores 15-LOX-1 protein expression and induces apoptosis. Down-regulation of 15-LOX-1 is an early event in the adenoma to carcinoma sequence, and reversal with celecoxib may represent one mechanism for chemoprevention of polyps or treatment of carcinomas.
- Published
- 2005
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