Fransız Yeni Dalga , Philippe Garrel, 1968 Hareketi , Les Amants Reguliers – Sıradan Aşıklar, Fil... more Fransız Yeni Dalga , Philippe Garrel, 1968 Hareketi , Les Amants Reguliers – Sıradan Aşıklar, Filmsel zaman.
A number of techniques developed to investigate protein structure and function depend on chemical... more A number of techniques developed to investigate protein structure and function depend on chemically modifying and/or labeling of proteins. However, in the case of homooligomeric proteins, the presence of multiple identical subunits obstructs the introduction of residue-specific labels to only one or several subunits, selectively. Here, in order to study the initial conformational changes of a homopentameric mechanosensitive ion channel during its gating, we developed a method for labeling a defined number of subunits of the channel with two different cysteine-specific compounds simultaneously. The first one is a light-sensitive channel activator that determines the degree of openness of the ion channel upon irradiation. The second one is a spin label, containing an unpaired electron, which allows following the resulting structural changes upon channel gating by electron paramagnetic resonance spectroscopy. With this method, we could open MscL into different sub-open states. As the number of light switches per channel increased, the intersubunit spin-spin interactions became less, indicating changes in intersubunit proximities and opening of the channel. The ability of controlled activation of MscL into different open states with a noninvasive trigger and following the resulting conformational changes by spectroscopy will pave the way for detailed spectroscopic studies in the area of mechanosensation.
Maintenance of genomic stability in mammalian cells is achieved by the efficient work of DNA repa... more Maintenance of genomic stability in mammalian cells is achieved by the efficient work of DNA repair mechanisms. Polymorphisms of DNA repair genes impair the DNA repair capacity and may lead to genetic instability and carcinogenesis. X-ray repair cross-complimenting group 1 (XRCC1) is one of the most important genes functioning in base excision repair pathway and a number of studies suggest that polymorphic forms of XRCC1 has a role in susceptibility to various kinds of cancer including breast, prostate, lung and bladder cancers. However, there are limited and contradictory data on the association between the XRCC1 polymorphisms and childhood acute lymphoblastic leukemia (ALL). In this study, we investigated the possible association of XRCC1 Arg399Gln and Arg194Gln variants with the risk of incidence of childhood ALL in Turkish population. The genotypes were determined with the use of PCR/RFLP techniques on 190 healthy controls and 167 ALL patients. For Arg399Gln polymorphism, the he...
Today it is well known that the interindividual variation in the activity of xenobiotic metaboliz... more Today it is well known that the interindividual variation in the activity of xenobiotic metabolizing enzymes and DNA repair genes could modify an individual's risk for several types of cancer. The observed effect for the risk of cancer development is more prominent when more than one polymorphism, especially those affecting xenobiotic metabolizing and as well DNA repair capacity are combined. We recently showed that DNA repair gene XRCC1 Arg399Gln polymorphism alone significantly increased the risk of childhood ALL 2.0-fold (OR: 2.0; p=0.04). Furthermore, its combination with CYP2E1 polymorphisms has stronger effect and increased the risk of childhood ALL 3.7 fold (OR: 3.7; p=0.049) (Tumer et al., 2010). In the current study, we investigated the possible association of microsomal epoxide hydrolase (EPHX1) exon 3 and exon 4 variants with the risk of incidence of childhood ALL in Turkish population comprised of 190 healthy controls and 167 ALL patients. EPHX1 is a phase I drug met...
Proceedings of the National Academy of Sciences, 2014
Mechanosensitive ion channels are sensors probing membrane tension in all species; despite their ... more Mechanosensitive ion channels are sensors probing membrane tension in all species; despite their importance and vital role in many cell functions, their gating mechanism remains to be elucidated. Here, we determined the conditions for releasing intact mechanosensitive channel of large conductance (MscL) proteins from their detergents in the gas phase using native ion mobility-mass spectrometry (IM-MS). By using IM-MS, we could detect the native mass of MscL from Escherichia coli, determine various global structural changes during its gating by measuring the rotationally averaged collision cross-sections, and show that it can function in the absence of a lipid bilayer. We could detect global conformational changes during MscL gating as small as 3%. Our findings will allow studying native structure of many other membrane proteins.
If we look at a simple organism such as a zebrafish under a microscope, we would see many cells w... more If we look at a simple organism such as a zebrafish under a microscope, we would see many cells working in harmony. If we zoomed in, we would observe each unit performing its own tasks in a special aqueous environment isolated from the other units by a lipid bilayer approximately 5 nm thick. These confined units are social: they communicate with one another by sensing and responding to the chemical changes in their environment through receptors and ion channels. These channels control the highly specific and selective passage of ions from one side of the cell to the other and are embedded in lipid bilayers. The movement of ions through ion channels supports excitation and electrical signaling in the nervous system. Ion channels have fascinated scientists not only because of their specificity and selectivity, but also for their functions, the serious consequences when they malfunction, and the other potential applications of these molecules. Light is a useful trigger to control and manipulate ion channels externally. With the many state-of-the-art optical technologies available, light offers a high degree of spatial and temporal control, millisecond precision, and noninvasive intervention and does not change the chemical environment of the system of interest. In this Account, we discuss research toward the dynamic control of lipid bilayer assembly and channel function, particularly the transport across the lipid bilayer-ion channel barrier of cells using light. We first summarize the manipulation of ion channel activity with light to modulate the channel's natural activity. Based on the type of photoswitch employed, we can achieve novel functionalities with these channels, and control neural activity. Then we discuss the recent developments in light-induced transport through lipid bilayers. We focus on three different approaches: the incorporation of photoswitchable copolymers into the lipids, the doping of the lipid bilayer with photosensitive amphiphiles and the preparation of the lipid bilayers solely from photoswitchable lipids. These examples reflect the versatility of what we can achieve by manipulating biological systems with light, from triggering the permeability of a specific area of a lipid bilayer to controlling the behavior of a whole organism.
ABSTRACT Metformin is a biguanide group antihyperglycemic agent that reduces the basal and postpr... more ABSTRACT Metformin is a biguanide group antihyperglycemic agent that reduces the basal and postprandial glucose level and increases glucose tolerance in patients with type II diabetes mellitus. The rarely observed side effects are nausea, vomiting, diarrhea, and abdominal pain. In some hypersensitive patients, mild erythema has been reported. In this case report, angioedema developed immediately after 1 dose of metformin usage.
Depression is often accompanied by cognitive impairment in humans and animals. Much less is known... more Depression is often accompanied by cognitive impairment in humans and animals. Much less is known about how cognitive competence is related to vulnerability to depression. The present study investigated the effect of previous exposure to a learning task on a depressogenic manipulation. Male Wistar rats (n=20) underwent 3 days of testing in a Y-maze (one trial/day) and were subsequently subjected to forced swimming tests (FSTs) a week later. The learning task involved finding a sweet food reward in all three arms of a symmetrical Y-Maze (45 x 15 x 45 cm). Latency to find and consume all three pellets was used to assess learning over three days. Subjects were administered two FSTs (of 15 min and 5 min durations, respectively) separated by 24 hr. Increased immobility in the second FST compared to the initial 5 min of the first FST is a sign of behavioral despair. Subjects were ranked as to whether their average latencies were in the top or the bottom 30 % of the group ('good' a...
Page 1. Antioxidative parameters in the opposite-leaved pondweed (Gronlendia densa) in response t... more Page 1. Antioxidative parameters in the opposite-leaved pondweed (Gronlendia densa) in response to nickel stress Dilek Demirezen Yilmaza* and Kadiriye Uruç Parlakb aErciyes University, Faculty of Science and Arts, Department ...
Fransız Yeni Dalga , Philippe Garrel, 1968 Hareketi , Les Amants Reguliers – Sıradan Aşıklar, Fil... more Fransız Yeni Dalga , Philippe Garrel, 1968 Hareketi , Les Amants Reguliers – Sıradan Aşıklar, Filmsel zaman.
A number of techniques developed to investigate protein structure and function depend on chemical... more A number of techniques developed to investigate protein structure and function depend on chemically modifying and/or labeling of proteins. However, in the case of homooligomeric proteins, the presence of multiple identical subunits obstructs the introduction of residue-specific labels to only one or several subunits, selectively. Here, in order to study the initial conformational changes of a homopentameric mechanosensitive ion channel during its gating, we developed a method for labeling a defined number of subunits of the channel with two different cysteine-specific compounds simultaneously. The first one is a light-sensitive channel activator that determines the degree of openness of the ion channel upon irradiation. The second one is a spin label, containing an unpaired electron, which allows following the resulting structural changes upon channel gating by electron paramagnetic resonance spectroscopy. With this method, we could open MscL into different sub-open states. As the number of light switches per channel increased, the intersubunit spin-spin interactions became less, indicating changes in intersubunit proximities and opening of the channel. The ability of controlled activation of MscL into different open states with a noninvasive trigger and following the resulting conformational changes by spectroscopy will pave the way for detailed spectroscopic studies in the area of mechanosensation.
Maintenance of genomic stability in mammalian cells is achieved by the efficient work of DNA repa... more Maintenance of genomic stability in mammalian cells is achieved by the efficient work of DNA repair mechanisms. Polymorphisms of DNA repair genes impair the DNA repair capacity and may lead to genetic instability and carcinogenesis. X-ray repair cross-complimenting group 1 (XRCC1) is one of the most important genes functioning in base excision repair pathway and a number of studies suggest that polymorphic forms of XRCC1 has a role in susceptibility to various kinds of cancer including breast, prostate, lung and bladder cancers. However, there are limited and contradictory data on the association between the XRCC1 polymorphisms and childhood acute lymphoblastic leukemia (ALL). In this study, we investigated the possible association of XRCC1 Arg399Gln and Arg194Gln variants with the risk of incidence of childhood ALL in Turkish population. The genotypes were determined with the use of PCR/RFLP techniques on 190 healthy controls and 167 ALL patients. For Arg399Gln polymorphism, the he...
Today it is well known that the interindividual variation in the activity of xenobiotic metaboliz... more Today it is well known that the interindividual variation in the activity of xenobiotic metabolizing enzymes and DNA repair genes could modify an individual's risk for several types of cancer. The observed effect for the risk of cancer development is more prominent when more than one polymorphism, especially those affecting xenobiotic metabolizing and as well DNA repair capacity are combined. We recently showed that DNA repair gene XRCC1 Arg399Gln polymorphism alone significantly increased the risk of childhood ALL 2.0-fold (OR: 2.0; p=0.04). Furthermore, its combination with CYP2E1 polymorphisms has stronger effect and increased the risk of childhood ALL 3.7 fold (OR: 3.7; p=0.049) (Tumer et al., 2010). In the current study, we investigated the possible association of microsomal epoxide hydrolase (EPHX1) exon 3 and exon 4 variants with the risk of incidence of childhood ALL in Turkish population comprised of 190 healthy controls and 167 ALL patients. EPHX1 is a phase I drug met...
Proceedings of the National Academy of Sciences, 2014
Mechanosensitive ion channels are sensors probing membrane tension in all species; despite their ... more Mechanosensitive ion channels are sensors probing membrane tension in all species; despite their importance and vital role in many cell functions, their gating mechanism remains to be elucidated. Here, we determined the conditions for releasing intact mechanosensitive channel of large conductance (MscL) proteins from their detergents in the gas phase using native ion mobility-mass spectrometry (IM-MS). By using IM-MS, we could detect the native mass of MscL from Escherichia coli, determine various global structural changes during its gating by measuring the rotationally averaged collision cross-sections, and show that it can function in the absence of a lipid bilayer. We could detect global conformational changes during MscL gating as small as 3%. Our findings will allow studying native structure of many other membrane proteins.
If we look at a simple organism such as a zebrafish under a microscope, we would see many cells w... more If we look at a simple organism such as a zebrafish under a microscope, we would see many cells working in harmony. If we zoomed in, we would observe each unit performing its own tasks in a special aqueous environment isolated from the other units by a lipid bilayer approximately 5 nm thick. These confined units are social: they communicate with one another by sensing and responding to the chemical changes in their environment through receptors and ion channels. These channels control the highly specific and selective passage of ions from one side of the cell to the other and are embedded in lipid bilayers. The movement of ions through ion channels supports excitation and electrical signaling in the nervous system. Ion channels have fascinated scientists not only because of their specificity and selectivity, but also for their functions, the serious consequences when they malfunction, and the other potential applications of these molecules. Light is a useful trigger to control and manipulate ion channels externally. With the many state-of-the-art optical technologies available, light offers a high degree of spatial and temporal control, millisecond precision, and noninvasive intervention and does not change the chemical environment of the system of interest. In this Account, we discuss research toward the dynamic control of lipid bilayer assembly and channel function, particularly the transport across the lipid bilayer-ion channel barrier of cells using light. We first summarize the manipulation of ion channel activity with light to modulate the channel's natural activity. Based on the type of photoswitch employed, we can achieve novel functionalities with these channels, and control neural activity. Then we discuss the recent developments in light-induced transport through lipid bilayers. We focus on three different approaches: the incorporation of photoswitchable copolymers into the lipids, the doping of the lipid bilayer with photosensitive amphiphiles and the preparation of the lipid bilayers solely from photoswitchable lipids. These examples reflect the versatility of what we can achieve by manipulating biological systems with light, from triggering the permeability of a specific area of a lipid bilayer to controlling the behavior of a whole organism.
ABSTRACT Metformin is a biguanide group antihyperglycemic agent that reduces the basal and postpr... more ABSTRACT Metformin is a biguanide group antihyperglycemic agent that reduces the basal and postprandial glucose level and increases glucose tolerance in patients with type II diabetes mellitus. The rarely observed side effects are nausea, vomiting, diarrhea, and abdominal pain. In some hypersensitive patients, mild erythema has been reported. In this case report, angioedema developed immediately after 1 dose of metformin usage.
Depression is often accompanied by cognitive impairment in humans and animals. Much less is known... more Depression is often accompanied by cognitive impairment in humans and animals. Much less is known about how cognitive competence is related to vulnerability to depression. The present study investigated the effect of previous exposure to a learning task on a depressogenic manipulation. Male Wistar rats (n=20) underwent 3 days of testing in a Y-maze (one trial/day) and were subsequently subjected to forced swimming tests (FSTs) a week later. The learning task involved finding a sweet food reward in all three arms of a symmetrical Y-Maze (45 x 15 x 45 cm). Latency to find and consume all three pellets was used to assess learning over three days. Subjects were administered two FSTs (of 15 min and 5 min durations, respectively) separated by 24 hr. Increased immobility in the second FST compared to the initial 5 min of the first FST is a sign of behavioral despair. Subjects were ranked as to whether their average latencies were in the top or the bottom 30 % of the group ('good' a...
Page 1. Antioxidative parameters in the opposite-leaved pondweed (Gronlendia densa) in response t... more Page 1. Antioxidative parameters in the opposite-leaved pondweed (Gronlendia densa) in response to nickel stress Dilek Demirezen Yilmaza* and Kadiriye Uruç Parlakb aErciyes University, Faculty of Science and Arts, Department ...
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