Angie Garcia | UNAD - Academia.edu (original) (raw)

Papers by Angie Garcia

Handbook of Research on Techno-Entrepreneurship, Third Edition, 2019

P2X receptors are cell surface cation channels activated by extracellular ATP (Khakh and North, 2... more P2X receptors are cell surface cation channels activated by extracellular ATP (Khakh and North, 2006; Burnstock, 2007; Surprenant and North, 2009). In addition to being present on the plasma membrane, some P2X receptors are also present within intracellular vesicular compartments (Ennion and Evans, 2001; Bobanovic et al., 2002; Toulmé et al., 2006; Fountain et al., 2007; Qureshi et al., 2007; Stokes and Surprenant, 2009). Seven P2X subunits comprise the P2X receptor family (P2X1–P2X7), with strong evidence to suggest that one type (P2X4) plays important roles in neuropathic pain (Tsuda et al., 2003; Coull et al., 2005). In these studies, the relevant sites of P2X4 expression appear to be resident immune cells called microglia (Tsuda et al., 2003). Thus, strategies that reduce or abolish P2X4 expression alleviate symptoms such as allodynia that are a hallmark of neuropathic pain models (Tsuda et al., 2003; Ulmann et al., 2008). In brief, these experiments suggest that one important d...

The study aims to gain insight into how social workers perceive their psychosocial work environme... more The study aims to gain insight into how social workers perceive their psychosocial work environment and examine whether this effects the performance of their duties. The study mainly addresses the shortcomings of the psychosocial work environment of Social Services and the implications it entails for social workers health and wellbeing. The psychosocial work environment includes physical and psychological factors therefore the study's interpretive framework consists of organizational theoretical and social psychological concepts and previous research on the subject. We examined the organizational and social psychological connections to social workers perception of their work environment with a qualitative approach. The empirical data was collected through interviews with four social workers in a municipality in central Sweden using a semi-structured interview guide. The results led to the conclusions that challenge our preconceptions and gave us a nuanced perspective on social w...

Antimicrobial agents and chemotherapy, Jan 2, 2018

Systemic candidiasis is a growing health care concern becoming even more challenging due to the g... more Systemic candidiasis is a growing health care concern becoming even more challenging due to the growing frequency of infections caused by multidrug resistant (MDR)Thus there is an urgent need for new therapeutic approaches to candidiasis, including strategies bioinspired by insights into natural host defense against fungal pathogens. The antifungal properties of θ-defensins, macrocyclic peptides expressed in tissues of Old World monkeys, were investigated against a panel of drug sensitive and drug resistant clinical isolates ofand non-albicansspp. Rhesus θ-defensin 1 (RTD-1), the prototype θ-defensin, was rapidly and potently fungicidal against drug sensitive and MDRstrains. Fungal killing occurred by cell permeabilization that was temporally correlated with ATP release and intracellular accumulation of reactive oxygen species (ROS). Killing by RTD-1 was compared with that of histatin 5 (Hst 5), an extensively characterized anticandidal peptide expressed in human saliva. RTD-1 kille...

It has been an honor for me to work under the advisement of Prof. Michael Marsella. I will foreve... more It has been an honor for me to work under the advisement of Prof. Michael Marsella. I will forever be indebted to him for his help and guidance. He has been an extraordinary advisor who has allowed me the freedom to explore any project I wanted and has always been extremely supportive and encouraging. Thank you. I would like to give a special thanks to my undergraduate lab advisor, Dr. Steve Angle for allowing me to work in his lab and introducing me to a career in research. His continued support throughout my graduate career has been greatly appreciated. I would also like to thank my committee members, Prof. Christopher Switzer and Prof. Catharine Larsen. Thank you to the Marsella group, past and present graduate students and undergrads. Thank you to Dr. Shohreh Rahbarnia for mentoring me as an undergrad and for her continued support throughout my graduate career. I would also like to give a very special thank you to future doctor Jenifer Nalbandian and Dr. Katherine Hawkins for allowing me to vent my frustrations, and for always taking my side; you truly are great friends. I also want to give a special thanks to Mrs. Maria Franco-Aguilar for her help, warmth, and kindness all these years. As well as anyone else who has helped bring me to this point. Thank you very much! I would like to thank Prof. Chia-En Chang for CB1/THC(an) docking studies and Drs. O. Salo-Ahen and A. Gonzalez for providing the CB 1 homology model used in these studies. I am also thankful to Dr. Dan Borchardt for the complete NMR analysis of the THCan-C5 isomers, help with NMR interpretation and with running NMR experiments, as well as Dr. Yi Meng. Dr. Rich Kondrat, Ron New, and Baback Bastin for mass spec samples. ! v! Above all else I would like to thank my family, especially my mom, Josefina Garcia and my dad, Jose Garcia. Your faith in me has given me the strength and courage to follow my dreams. None of this would have been possible without you. Thank you for believing in me, even when I found it hard to believe in myself. Thank you for showing me that with hard work, sacrifice, and dedication great things can happen. Thank you to my aunt, Maria (Bola) Macias who has been like a second mom to my siblings and me. Thank you to my sisters, Maria Salazar and Alicia Cataudella, for being great role models. Thank you to my brothers, Jose (Junier) Garcia, and

The Faseb Journal, Mar 1, 2008

Angewandte Chemie, 2015

Nucleophilic substitution reactions of acetals with benzyloxy groups four carbon atoms away can b... more Nucleophilic substitution reactions of acetals with benzyloxy groups four carbon atoms away can be highly diastereoselective. The selectivity in several cases increased as the reactivity of the nucleophile increased, in violation of the reactivity-selectivity principle. The increase in selectivity with reactivity suggests that multiple conformational isomers of reactive intermediates can give rise to the products.

The Journal of Organic Chemistry, 2015

The hydrolysis of 4-alkoxy-substituted acetals were accelerated by about 20-fold compared to ster... more The hydrolysis of 4-alkoxy-substituted acetals were accelerated by about 20-fold compared to sterically comparable substrates that do not have an alkoxy group. Rate accelerations are largest when the two functional groups are linked by a flexible cyclic tether. When controlled for the inductive destabilization, an alkoxy group, can accelerate acetal hydrolysis by up to 200-fold. The difference in rates of acetal hydrolysis between a substrate where the alkoxy group was tethered to the acetal group by a five-membered ring compared to one where it was tethered by an eight-membered ring was less than 100-fold, suggesting that fused-ring intermediates were not formed. By comparison, the difference in rates of solvolysis of structurally related tosylates were nearly 10^6-fold between the eight-membered and five-membered ring series. This observation implicates neighboring-group participation in the solvolysis of tosylates but not in the hydrolysis of acetals. The acceleration of acetal hydrolysis by an alkoxy group is better explained by electrostatic stabilization of intermediates that accumulate positive charge at the acetal carbon atom.

Angewandte Chemie, 2015

In contrast to observations with carbohydrates, experiments with 4-alkoxy-substituted acetals ind... more In contrast to observations with carbohydrates, experiments with 4-alkoxy-substituted acetals indicate that an alkoxy group can accelerate acetal hydrolysis by up to 20-fold compared to substrates without an alkoxy group. The acceleration of ionization in more flexible acetals can be up to 200-fold when compensated for inductive effects.

Current Molecular Pharmacology, 2010

Cyclotides are a growing family of large plant-derived backbone-cyclized polypeptides (≈30 amino ... more Cyclotides are a growing family of large plant-derived backbone-cyclized polypeptides (≈30 amino acids long) that share a disulfide-stabilized core characterized by an unusual knotted structure. Their unique circular backbone topology and knotted arrangement of three disulfide bonds makes them exceptionally stable to thermal, chemical, and enzymatic degradation compared to other peptides of similar size. Currently more than 100 sequences of different cyclotides have been characterized and the number is expected to increase dramatically in the coming years. Considering their stability, biological activities and ability to cross the cell membrane, cyclotides can be exploited to develop new peptide-based drugs with high potential for success. The cyclotide scaffold can be engineered or evolved using molecular evolution to inhibit proteinprotein interactions implicated in cancer and other human diseases, or design new antimicrobial. The present review reports the biological diversity and therapeutic potential of natural and engineered cyclotides.

Pharmaceutical research

Protein microarray technology possesses some of the greatest potential for providing direct infor... more Protein microarray technology possesses some of the greatest potential for providing direct information on protein function and potential drug targets. For example, functional protein microarrays are ideal tools suited for the mapping of biological pathways. They can be used to study most major types of interactions and enzymatic activities that take place in biochemical pathways and have been used for the analysis of simultaneous multiple biomolecular interactions involving protein-protein, protein-lipid, protein-DNA and protein-small molecule interactions. Because of this unique ability to analyze many kinds of molecular interactions en masse, the requirement of very small sample amount and the potential to be miniaturized and automated, protein microarrays are extremely well suited for protein profiling, drug discovery, drug target identification and clinical prognosis and diagnosis. The aim of this review is to summarize the most recent developments in the production, applications and analysis of protein microarrays.

Journal of the …, 2011

Defensins comprise a potent class of membrane disruptive antimicrobial peptides (AMPs) with well-... more Defensins comprise a potent class of membrane disruptive antimicrobial peptides (AMPs) with well-characterized broad spectrum and selective microbicidal effects. By using high-resolution synchrotron small-angle X-ray scattering to investigate interactions between ...

NASSP Bulletin, 1986

Although decision making by consensus takes time, cooperation, and practice, the results are not ... more Although decision making by consensus takes time, cooperation, and practice, the results are not only good decisions, but also a sense of ownership and satisfaction among faculty members involved in the process. ... ANGIE GARCIA is principal at Oak-land Jr. High School, Lake ...

Biochemistry, 2011

Defensins are antimicrobial peptides that are important in the innate immune defense of mammals. ... more Defensins are antimicrobial peptides that are important in the innate immune defense of mammals. Upon stimulation by bacterial antigens, enteric α-defensins are secreted into the intestinal lumen where they have potent microbicidal activities. Cryptdin-4 (Crp4) is an α-defensin expressed in Paneth cells of the mouse small intestine and the most bactericidal of the known cryptdin isoforms. The structure of Crp4 consists of a triple-stranded antiparallel β-sheet but lacks three amino acids between the fourth and fifth cysteine residues, making them distinct from other α-defensins. The structure also reveals that the α-amino and C-terminal carboxylic groups are in the proximity of each other (d ≈ 3 Å) in the folded structure. We present here the biosynthesis of backbone-cyclized Crp4 using a modified protein splicing unit or intein. Our data show that cyclized Crp4 can be biosynthesized by using this approach both in vitro and in vivo, although the expression yield was significantly lower when the protein was produced inside the cell. The resulting cyclic defensins retained the native α-defensin fold and showed equivalent or better microbicidal activities against several Gram-positive and Gram-negative bacteria when compared to native Crp4. No detectable hemolytic activity against human red blood cells was observed for either native Crp4 or its cyclized variants. Moreover, both forms of Crp4 also showed high stability to degradation when incubated with human serum. Altogether, these results indicate the potential for backbone-cyclized defensins in the development of novel peptide-based antimicrobial compounds.

Journal of the American Chemical Society, 2009

Thermal isomerization of CBC(an) to THC(an) [nonaromatic analogues of plant cannabinoids cannabic... more Thermal isomerization of CBC(an) to THC(an) [nonaromatic analogues of plant cannabinoids cannabichromene (CBC) and Delta(1)-tetrahydrocannabinol (THC), respectively] is predicted in silico and demonstrated experimentally. Density functional theory calculations support a similar isomerization mechanism for the corresponding plant cannabinoids. Docking studies suggest that THC(an), although nonaromatic, has a CB(1) receptor binding affinity similar to that of natural THC.

http://dialnet.unirioja.es/servlet/articulo?codigo=3877523 -------------------------- En este art... more http://dialnet.unirioja.es/servlet/articulo?codigo=3877523 -------------------------- En este artículo el autor indaga acerca del alcance de la “teoría mimética” de René Girard para comprender la migración. Con este propósito, hace una breve descripción de la “teoría mimética” y una caracterización de la migración. Posteriormente, plantea la necesidad de nuevas perspectivas investigativas sobre la migración, que vayan más allá del abordaje positivista de las ciencias humanas que deja de lado el aporte de una comprensión filosófica. En este sentido, la filosofía girardeana resulta pertinente para la comprensión de cierto tipo de migración: inmigración irregular, desplazamiento forzado y refugio. Finalmente, propone una praxis que evite, o al menos minimice, el proceso mimético persecutorio relacionado con este tipo de migración. ----------------------------------- In this article the author explores the extent of René Girard’s “mimetic theory” to understand migration phenomenon. To t...

Molecular BioSystems, 2012

Defensins are antimicrobial peptides that are important in the innate immune defense of mammals. ... more Defensins are antimicrobial peptides that are important in the innate immune defense of mammals. In contrast to mammalian a-and b-defensins, rhesus y-defensin-1 (RTD-1) comprises only 18 amino acids stabilized by three disulfide bonds and an unusual backbone cyclic topology. In this work we report for the first time the recombinant expression of the fully folded y-defensin RTD-1 using a bacterial expression system. This was accomplished using an intramolecular native chemical ligation in combination with a ...

Journal of General Physiology, 2010

We investigated the properties and regulation of P2X receptors in immortalized C8-B4 cells of cer... more We investigated the properties and regulation of P2X receptors in immortalized C8-B4 cells of cerebellar microglial origin. Resting C8-B4 cells expressed virtually no functional P2X receptors, but largely increased functional expression of P2X4 receptors within 2-6 h of entering the activated state. Using real-time polymerase chain reaction, we found that P2X4 transcripts were increased during the activated state by 2.4-fold, but this increase was not reflected by a parallel increase in total P2X4 proteins. In resting C8-B4 cells, P2X4 subunits were mainly localized within intracellular compartments, including lysosomes. We found that cell surface P2X4 receptor levels increased by 3.5-fold during the activated state. This change was accompanied by a decrease in the lysosomal pool of P2X4 proteins. We next exploited our findings with C8-B4 cells to investigate the mechanism by which antidepressants reduce P2X4 responses. We found little evidence to suggest that several antidepressants were antagonists of P2X4 receptors in C8-B4 cells. However, we found that moderate concentrations of the same antidepressants reduced P2X4 responses in activated microglia by affecting lysosomal function, which indirectly reduced cell surface P2X4 levels. In summary, our data suggest that activated C8-B4 cells express P2X4 receptors when the membrane insertion of these proteins by lysosomal secretion exceeds their removal, and that antidepressants indirectly reduce P2X4 responses by interfering with lysosomal trafficking.

Asn Neuro, 2010

Vaccine-based autoimmune (anti-amyloid) treatments are currently being examined for their therape... more Vaccine-based autoimmune (anti-amyloid) treatments are currently being examined for their therapeutic potential in Alzheimer's disease. In the present study we examined, in a transgenic model of amyloid pathology, the expression of two molecules previously implicated in decreasing the severity of autoimmune responses: TREM2 (triggering receptor expressed on myeloid cells 2) and the intracellular tolerance-associated transcript, Tmem176b (transmembrane domain protein 176b). In situ hybridization analysis revealed that both molecules were highly expressed in plaque-associated microglia, but their expression defined two different zones of plaque-associated activation. Tmem176b expression was highest in the inner zone of amyloid plaques, whereas TREM2 expression was highest in the outer zone. Induced expression of TREM2 occurred coincident with detection of thioflavine-S-positive amyloid deposits. Transfection studies revealed that expression of TREM2 correlated negatively with motility, but correlated positively with the ability of microglia to stimulate CD4 + T-cell proliferation, TNF (tumour necrosis factor) and CCL2 (chemokine ligand 2) production, but not IFNc (interferon c) production. TREM2 expression also showed a positive correlation with amyloid phagocytosis in unactivated cells. However, activating cells with LPS (lipopolysaccharide), but not IFNc, reduced the correlation between TREM2 expression and phagocytosis. Transfection of Tmem176b into both microglial and macrophage cell lines increased apoptosis. Taken together, these data suggest that, in vivo, Tmem176b + cells in closest apposition to amyloid may be the least able to clear amyloid. Conversely, the phagocytic TREM2 + microglia on the plaque outer zones are positioned to capture and present self-antigens to CNS (central nervous system)-infiltrating lymphocytes without promoting pro-inflammatory lymphocyte responses. Instead, plaque-associated TREM2 + microglia have the potential to evoke neuroprotective immune responses that may serve to support CNS function during pro-inflammatory anti-amyloid immune therapies.

Handbook of Research on Techno-Entrepreneurship, Third Edition, 2019

P2X receptors are cell surface cation channels activated by extracellular ATP (Khakh and North, 2... more P2X receptors are cell surface cation channels activated by extracellular ATP (Khakh and North, 2006; Burnstock, 2007; Surprenant and North, 2009). In addition to being present on the plasma membrane, some P2X receptors are also present within intracellular vesicular compartments (Ennion and Evans, 2001; Bobanovic et al., 2002; Toulmé et al., 2006; Fountain et al., 2007; Qureshi et al., 2007; Stokes and Surprenant, 2009). Seven P2X subunits comprise the P2X receptor family (P2X1–P2X7), with strong evidence to suggest that one type (P2X4) plays important roles in neuropathic pain (Tsuda et al., 2003; Coull et al., 2005). In these studies, the relevant sites of P2X4 expression appear to be resident immune cells called microglia (Tsuda et al., 2003). Thus, strategies that reduce or abolish P2X4 expression alleviate symptoms such as allodynia that are a hallmark of neuropathic pain models (Tsuda et al., 2003; Ulmann et al., 2008). In brief, these experiments suggest that one important d...

The study aims to gain insight into how social workers perceive their psychosocial work environme... more The study aims to gain insight into how social workers perceive their psychosocial work environment and examine whether this effects the performance of their duties. The study mainly addresses the shortcomings of the psychosocial work environment of Social Services and the implications it entails for social workers health and wellbeing. The psychosocial work environment includes physical and psychological factors therefore the study's interpretive framework consists of organizational theoretical and social psychological concepts and previous research on the subject. We examined the organizational and social psychological connections to social workers perception of their work environment with a qualitative approach. The empirical data was collected through interviews with four social workers in a municipality in central Sweden using a semi-structured interview guide. The results led to the conclusions that challenge our preconceptions and gave us a nuanced perspective on social w...

Antimicrobial agents and chemotherapy, Jan 2, 2018

Systemic candidiasis is a growing health care concern becoming even more challenging due to the g... more Systemic candidiasis is a growing health care concern becoming even more challenging due to the growing frequency of infections caused by multidrug resistant (MDR)Thus there is an urgent need for new therapeutic approaches to candidiasis, including strategies bioinspired by insights into natural host defense against fungal pathogens. The antifungal properties of θ-defensins, macrocyclic peptides expressed in tissues of Old World monkeys, were investigated against a panel of drug sensitive and drug resistant clinical isolates ofand non-albicansspp. Rhesus θ-defensin 1 (RTD-1), the prototype θ-defensin, was rapidly and potently fungicidal against drug sensitive and MDRstrains. Fungal killing occurred by cell permeabilization that was temporally correlated with ATP release and intracellular accumulation of reactive oxygen species (ROS). Killing by RTD-1 was compared with that of histatin 5 (Hst 5), an extensively characterized anticandidal peptide expressed in human saliva. RTD-1 kille...

It has been an honor for me to work under the advisement of Prof. Michael Marsella. I will foreve... more It has been an honor for me to work under the advisement of Prof. Michael Marsella. I will forever be indebted to him for his help and guidance. He has been an extraordinary advisor who has allowed me the freedom to explore any project I wanted and has always been extremely supportive and encouraging. Thank you. I would like to give a special thanks to my undergraduate lab advisor, Dr. Steve Angle for allowing me to work in his lab and introducing me to a career in research. His continued support throughout my graduate career has been greatly appreciated. I would also like to thank my committee members, Prof. Christopher Switzer and Prof. Catharine Larsen. Thank you to the Marsella group, past and present graduate students and undergrads. Thank you to Dr. Shohreh Rahbarnia for mentoring me as an undergrad and for her continued support throughout my graduate career. I would also like to give a very special thank you to future doctor Jenifer Nalbandian and Dr. Katherine Hawkins for allowing me to vent my frustrations, and for always taking my side; you truly are great friends. I also want to give a special thanks to Mrs. Maria Franco-Aguilar for her help, warmth, and kindness all these years. As well as anyone else who has helped bring me to this point. Thank you very much! I would like to thank Prof. Chia-En Chang for CB1/THC(an) docking studies and Drs. O. Salo-Ahen and A. Gonzalez for providing the CB 1 homology model used in these studies. I am also thankful to Dr. Dan Borchardt for the complete NMR analysis of the THCan-C5 isomers, help with NMR interpretation and with running NMR experiments, as well as Dr. Yi Meng. Dr. Rich Kondrat, Ron New, and Baback Bastin for mass spec samples. ! v! Above all else I would like to thank my family, especially my mom, Josefina Garcia and my dad, Jose Garcia. Your faith in me has given me the strength and courage to follow my dreams. None of this would have been possible without you. Thank you for believing in me, even when I found it hard to believe in myself. Thank you for showing me that with hard work, sacrifice, and dedication great things can happen. Thank you to my aunt, Maria (Bola) Macias who has been like a second mom to my siblings and me. Thank you to my sisters, Maria Salazar and Alicia Cataudella, for being great role models. Thank you to my brothers, Jose (Junier) Garcia, and

The Faseb Journal, Mar 1, 2008

Angewandte Chemie, 2015

Nucleophilic substitution reactions of acetals with benzyloxy groups four carbon atoms away can b... more Nucleophilic substitution reactions of acetals with benzyloxy groups four carbon atoms away can be highly diastereoselective. The selectivity in several cases increased as the reactivity of the nucleophile increased, in violation of the reactivity-selectivity principle. The increase in selectivity with reactivity suggests that multiple conformational isomers of reactive intermediates can give rise to the products.

The Journal of Organic Chemistry, 2015

The hydrolysis of 4-alkoxy-substituted acetals were accelerated by about 20-fold compared to ster... more The hydrolysis of 4-alkoxy-substituted acetals were accelerated by about 20-fold compared to sterically comparable substrates that do not have an alkoxy group. Rate accelerations are largest when the two functional groups are linked by a flexible cyclic tether. When controlled for the inductive destabilization, an alkoxy group, can accelerate acetal hydrolysis by up to 200-fold. The difference in rates of acetal hydrolysis between a substrate where the alkoxy group was tethered to the acetal group by a five-membered ring compared to one where it was tethered by an eight-membered ring was less than 100-fold, suggesting that fused-ring intermediates were not formed. By comparison, the difference in rates of solvolysis of structurally related tosylates were nearly 10^6-fold between the eight-membered and five-membered ring series. This observation implicates neighboring-group participation in the solvolysis of tosylates but not in the hydrolysis of acetals. The acceleration of acetal hydrolysis by an alkoxy group is better explained by electrostatic stabilization of intermediates that accumulate positive charge at the acetal carbon atom.

Angewandte Chemie, 2015

In contrast to observations with carbohydrates, experiments with 4-alkoxy-substituted acetals ind... more In contrast to observations with carbohydrates, experiments with 4-alkoxy-substituted acetals indicate that an alkoxy group can accelerate acetal hydrolysis by up to 20-fold compared to substrates without an alkoxy group. The acceleration of ionization in more flexible acetals can be up to 200-fold when compensated for inductive effects.

Current Molecular Pharmacology, 2010

Cyclotides are a growing family of large plant-derived backbone-cyclized polypeptides (≈30 amino ... more Cyclotides are a growing family of large plant-derived backbone-cyclized polypeptides (≈30 amino acids long) that share a disulfide-stabilized core characterized by an unusual knotted structure. Their unique circular backbone topology and knotted arrangement of three disulfide bonds makes them exceptionally stable to thermal, chemical, and enzymatic degradation compared to other peptides of similar size. Currently more than 100 sequences of different cyclotides have been characterized and the number is expected to increase dramatically in the coming years. Considering their stability, biological activities and ability to cross the cell membrane, cyclotides can be exploited to develop new peptide-based drugs with high potential for success. The cyclotide scaffold can be engineered or evolved using molecular evolution to inhibit proteinprotein interactions implicated in cancer and other human diseases, or design new antimicrobial. The present review reports the biological diversity and therapeutic potential of natural and engineered cyclotides.

Pharmaceutical research

Protein microarray technology possesses some of the greatest potential for providing direct infor... more Protein microarray technology possesses some of the greatest potential for providing direct information on protein function and potential drug targets. For example, functional protein microarrays are ideal tools suited for the mapping of biological pathways. They can be used to study most major types of interactions and enzymatic activities that take place in biochemical pathways and have been used for the analysis of simultaneous multiple biomolecular interactions involving protein-protein, protein-lipid, protein-DNA and protein-small molecule interactions. Because of this unique ability to analyze many kinds of molecular interactions en masse, the requirement of very small sample amount and the potential to be miniaturized and automated, protein microarrays are extremely well suited for protein profiling, drug discovery, drug target identification and clinical prognosis and diagnosis. The aim of this review is to summarize the most recent developments in the production, applications and analysis of protein microarrays.

Journal of the …, 2011

Defensins comprise a potent class of membrane disruptive antimicrobial peptides (AMPs) with well-... more Defensins comprise a potent class of membrane disruptive antimicrobial peptides (AMPs) with well-characterized broad spectrum and selective microbicidal effects. By using high-resolution synchrotron small-angle X-ray scattering to investigate interactions between ...

NASSP Bulletin, 1986

Although decision making by consensus takes time, cooperation, and practice, the results are not ... more Although decision making by consensus takes time, cooperation, and practice, the results are not only good decisions, but also a sense of ownership and satisfaction among faculty members involved in the process. ... ANGIE GARCIA is principal at Oak-land Jr. High School, Lake ...

Biochemistry, 2011

Defensins are antimicrobial peptides that are important in the innate immune defense of mammals. ... more Defensins are antimicrobial peptides that are important in the innate immune defense of mammals. Upon stimulation by bacterial antigens, enteric α-defensins are secreted into the intestinal lumen where they have potent microbicidal activities. Cryptdin-4 (Crp4) is an α-defensin expressed in Paneth cells of the mouse small intestine and the most bactericidal of the known cryptdin isoforms. The structure of Crp4 consists of a triple-stranded antiparallel β-sheet but lacks three amino acids between the fourth and fifth cysteine residues, making them distinct from other α-defensins. The structure also reveals that the α-amino and C-terminal carboxylic groups are in the proximity of each other (d ≈ 3 Å) in the folded structure. We present here the biosynthesis of backbone-cyclized Crp4 using a modified protein splicing unit or intein. Our data show that cyclized Crp4 can be biosynthesized by using this approach both in vitro and in vivo, although the expression yield was significantly lower when the protein was produced inside the cell. The resulting cyclic defensins retained the native α-defensin fold and showed equivalent or better microbicidal activities against several Gram-positive and Gram-negative bacteria when compared to native Crp4. No detectable hemolytic activity against human red blood cells was observed for either native Crp4 or its cyclized variants. Moreover, both forms of Crp4 also showed high stability to degradation when incubated with human serum. Altogether, these results indicate the potential for backbone-cyclized defensins in the development of novel peptide-based antimicrobial compounds.

Journal of the American Chemical Society, 2009

Thermal isomerization of CBC(an) to THC(an) [nonaromatic analogues of plant cannabinoids cannabic... more Thermal isomerization of CBC(an) to THC(an) [nonaromatic analogues of plant cannabinoids cannabichromene (CBC) and Delta(1)-tetrahydrocannabinol (THC), respectively] is predicted in silico and demonstrated experimentally. Density functional theory calculations support a similar isomerization mechanism for the corresponding plant cannabinoids. Docking studies suggest that THC(an), although nonaromatic, has a CB(1) receptor binding affinity similar to that of natural THC.

http://dialnet.unirioja.es/servlet/articulo?codigo=3877523 -------------------------- En este art... more http://dialnet.unirioja.es/servlet/articulo?codigo=3877523 -------------------------- En este artículo el autor indaga acerca del alcance de la “teoría mimética” de René Girard para comprender la migración. Con este propósito, hace una breve descripción de la “teoría mimética” y una caracterización de la migración. Posteriormente, plantea la necesidad de nuevas perspectivas investigativas sobre la migración, que vayan más allá del abordaje positivista de las ciencias humanas que deja de lado el aporte de una comprensión filosófica. En este sentido, la filosofía girardeana resulta pertinente para la comprensión de cierto tipo de migración: inmigración irregular, desplazamiento forzado y refugio. Finalmente, propone una praxis que evite, o al menos minimice, el proceso mimético persecutorio relacionado con este tipo de migración. ----------------------------------- In this article the author explores the extent of René Girard’s “mimetic theory” to understand migration phenomenon. To t...

Molecular BioSystems, 2012

Defensins are antimicrobial peptides that are important in the innate immune defense of mammals. ... more Defensins are antimicrobial peptides that are important in the innate immune defense of mammals. In contrast to mammalian a-and b-defensins, rhesus y-defensin-1 (RTD-1) comprises only 18 amino acids stabilized by three disulfide bonds and an unusual backbone cyclic topology. In this work we report for the first time the recombinant expression of the fully folded y-defensin RTD-1 using a bacterial expression system. This was accomplished using an intramolecular native chemical ligation in combination with a ...

Journal of General Physiology, 2010

We investigated the properties and regulation of P2X receptors in immortalized C8-B4 cells of cer... more We investigated the properties and regulation of P2X receptors in immortalized C8-B4 cells of cerebellar microglial origin. Resting C8-B4 cells expressed virtually no functional P2X receptors, but largely increased functional expression of P2X4 receptors within 2-6 h of entering the activated state. Using real-time polymerase chain reaction, we found that P2X4 transcripts were increased during the activated state by 2.4-fold, but this increase was not reflected by a parallel increase in total P2X4 proteins. In resting C8-B4 cells, P2X4 subunits were mainly localized within intracellular compartments, including lysosomes. We found that cell surface P2X4 receptor levels increased by 3.5-fold during the activated state. This change was accompanied by a decrease in the lysosomal pool of P2X4 proteins. We next exploited our findings with C8-B4 cells to investigate the mechanism by which antidepressants reduce P2X4 responses. We found little evidence to suggest that several antidepressants were antagonists of P2X4 receptors in C8-B4 cells. However, we found that moderate concentrations of the same antidepressants reduced P2X4 responses in activated microglia by affecting lysosomal function, which indirectly reduced cell surface P2X4 levels. In summary, our data suggest that activated C8-B4 cells express P2X4 receptors when the membrane insertion of these proteins by lysosomal secretion exceeds their removal, and that antidepressants indirectly reduce P2X4 responses by interfering with lysosomal trafficking.

Asn Neuro, 2010

Vaccine-based autoimmune (anti-amyloid) treatments are currently being examined for their therape... more Vaccine-based autoimmune (anti-amyloid) treatments are currently being examined for their therapeutic potential in Alzheimer's disease. In the present study we examined, in a transgenic model of amyloid pathology, the expression of two molecules previously implicated in decreasing the severity of autoimmune responses: TREM2 (triggering receptor expressed on myeloid cells 2) and the intracellular tolerance-associated transcript, Tmem176b (transmembrane domain protein 176b). In situ hybridization analysis revealed that both molecules were highly expressed in plaque-associated microglia, but their expression defined two different zones of plaque-associated activation. Tmem176b expression was highest in the inner zone of amyloid plaques, whereas TREM2 expression was highest in the outer zone. Induced expression of TREM2 occurred coincident with detection of thioflavine-S-positive amyloid deposits. Transfection studies revealed that expression of TREM2 correlated negatively with motility, but correlated positively with the ability of microglia to stimulate CD4 + T-cell proliferation, TNF (tumour necrosis factor) and CCL2 (chemokine ligand 2) production, but not IFNc (interferon c) production. TREM2 expression also showed a positive correlation with amyloid phagocytosis in unactivated cells. However, activating cells with LPS (lipopolysaccharide), but not IFNc, reduced the correlation between TREM2 expression and phagocytosis. Transfection of Tmem176b into both microglial and macrophage cell lines increased apoptosis. Taken together, these data suggest that, in vivo, Tmem176b + cells in closest apposition to amyloid may be the least able to clear amyloid. Conversely, the phagocytic TREM2 + microglia on the plaque outer zones are positioned to capture and present self-antigens to CNS (central nervous system)-infiltrating lymphocytes without promoting pro-inflammatory lymphocyte responses. Instead, plaque-associated TREM2 + microglia have the potential to evoke neuroprotective immune responses that may serve to support CNS function during pro-inflammatory anti-amyloid immune therapies.