Lorena Ramirez - Academia.edu (original) (raw)
Papers by Lorena Ramirez
Proceedings of the 2nd World Congress on New Technologies, Jun 1, 2017
Problemas del Desarrollo. Revista Latinoamericana de Economía, 2009
Se analizan las organizaciones de productores de sorgo del estado de Guanajuato y el acceso de és... more Se analizan las organizaciones de productores de sorgo del estado de Guanajuato y el acceso de éstas a los programas de apoyo orientados a la comercialización del grano. Para ello, se aplicaron entrevistas abiertas a productores, a representantes de organizaciones y a funcionarios de los distintos niveles de gobierno. 89% de las organizaciones estudiadas tienen al menos catorce años de antigüedad, se integran en promedio con 62 productores y su actividad está orientada fundamentalmente a la comercialización de granos, la gestión de crédito y la captación de los apoyos federales para la comercialización. Se concluye que las organizaciones bajo estudio tienen dificultades para acceder a los apoyos a la comercialización, debido a que son pequeñas, con baja capacidad de almacenaje y de acceso limitado al financiamiento.
Environmental Science and Pollution Research, 2018
Metal contamination is a recurring problem in Peru, caused mainly by mine tailings from a past ac... more Metal contamination is a recurring problem in Peru, caused mainly by mine tailings from a past active mining activity. The Ancash region has the largest number of environmental liabilities, which mobilizes high levels of metals and acid drainages into soils and freshwater sources, posing a standing risk on human and environmental health. Native plant species spontaneously growing on naturally acidified soils and acid mine tailings show a unique tolerance to high metal concentrations and are thus potential candidates for soil phytoremediation. However, little is known about their propagation capacity and metal accumulation under controlled conditions. In this study, we aimed at characterizing nine native plant species, previously identified as potential hyperaccumulators, from areas impacted by mine tailings in the Ancash region. Plants were grown on mine soils under greenhouse conditions during 5 months, after which the concentration of Cd, Cu, Ni, Pb, and Zn was analyzed in roots, shoots, and soils. The bioaccumulation (BAF) and translocation factor (TF) were calculated to determine the amount of each metal accumulated in the roots and shoots and to identify which species could be better suited for phytoremediation purposes. Soil samples contained high Cd (6.50-49.80 mg/kg), Cu (159.50-1187.00 mg/kg), Ni (3.50-8.70 mg/kg), Pb (1707.00-4243.00 mg/kg), and Zn (909.00-7100.00 mg/kg) concentrations exceeding national environmental quality standards. After exposure to mine tailings, concentrations of metals in shoots were highest in
PloS one, 2018
In families at risk from monogenic diseases affected offspring, it is fundamental the development... more In families at risk from monogenic diseases affected offspring, it is fundamental the development of a suitable Double Factor Preimplantation Genetic Testing (DF-PGT) method for both single-gene analysis and chromosome complement screening. Aneuploidy is not only a major issue in advanced-maternal-age patients and balanced translocation carriers, but also the aneuploidy rate is extremely high in patients undergoing in vitro fertilization (IVF), even in young donors. To adequate NGS technology to the DF-PGT strategy four different whole genome amplification systems (Sureplex, MALBAC, and two multiple displacement amplification systems-MDA) were tested using TruSight One panel on cell lines and blastocyst trophectoderm biopsies-TE. Embryo cytogenetic status was analyzed by Nexus software. Sureplex and MALBAC DNA products were considered not suitable for PGT diagnosis due to inconsistent and poor results on Trusight one (TSO) panel. Results obtained with both MDA based methods (GEH-MDA...
Physical Therapy, 2003
Background and Purpose. Little research has been done regarding the attitudes and behaviors of ph... more Background and Purpose. Little research has been done regarding the attitudes and behaviors of physical therapists relative to the use of evidence in practice. The purposes of this study were to describe the beliefs, attitudes, knowledge, and behaviors of physical therapist members of the American Physical Therapy Association (APTA) as they relate to evidence-based practice (EBP) and to generate hypotheses about the relationship between these attributes and personal and practice characteristics of the respondents. Methods. A survey of a random sample of physical therapist members of APTA resulted in a 48.8% return rate and a sample of 488 that was fairly representative of the national membership. Participants completed a questionnaire designed to determine beliefs, attitudes, knowledge, and behaviors regarding EBP, as well as demographic information about themselves and their practice settings. Responses were summarized for each item, and logistic regression analyses were used to ex...
The American Journal of Tropical Medicine and Hygiene, 1998
We report a human immunodeficiency virus (HIV)-infected man with chronic Chagas' disease who deve... more We report a human immunodeficiency virus (HIV)-infected man with chronic Chagas' disease who developed a congestive heart failure that could not be clinically controlled. Endomyocardial biopsy revealed severe myocarditis and the xenodiagnosis result was positive, but Trypanosoma cruzi by direct microscopic examination of the blood was found only four months after the symptoms had started. Treatment with benznidazole was effective in reducing parasitemia, stabilizing the clinical status, and controlling tissue damage related to the parasite. Although the finding of T. cruzi trypomastigotes by direct microscopic examination of the blood has been considered the mark of Chagas' reactivation in immunocompromised patients with chronic disease, in this case it was a late finding.
PloS one, 2017
Venous thromboembolism is a complex disease with a high heritability. There are significant assoc... more Venous thromboembolism is a complex disease with a high heritability. There are significant associations among Factor XI (FXI) levels and SNPs in the KNG1 and F11 loci. Our aim was to identify the genetic variation of KNG1 and F11 that might account for the variability of FXI levels. The KNG1 and F11 loci were sequenced completely in 110 unrelated individuals from the GAIT-2 (Genetic Analysis of Idiopathic Thrombophilia 2) Project using Next Generation Sequencing on an Illumina MiSeq. The GAIT-2 Project is a study of 935 individuals in 35 extended Spanish families selected through a proband with idiopathic thrombophilia. Among the 110 individuals, a subset of 40 individuals was chosen as a discovery sample for identifying variants. A total of 762 genetic variants were detected. Several significant associations were established among common variants and low-frequency variants sets in KNG1 and F11 with FXI levels using the PLINK and SKAT packages. Among these associations, those of rs...
PloS one, 2017
Hepatocyte poliploidization is an age-dependent process, being cytokinesis failure the main mecha... more Hepatocyte poliploidization is an age-dependent process, being cytokinesis failure the main mechanism of polyploid hepatocyte formation. Our aim was to study the role of p38α MAPK in the regulation of actin cytoskeleton and cytokinesis in hepatocytes during development and aging. Wild type and p38α liver-specific knock out mice at different ages (after weaning, adults and old) were used. We show that p38α MAPK deficiency induces actin disassembly upon aging and also cytokinesis failure leading to enhanced binucleation. Although the steady state levels of cyclin D1 in wild type and p38α knock out old livers remained unaffected, cyclin B1- a marker for G2/M transition- was significantly overexpressed in p38α knock out mice. Our findings suggest that hepatocytes do enter into S phase but they do not complete cell division upon p38α deficiency leading to cytokinesis failure and binucleation. Moreover, old liver-specific p38α MAPK knock out mice exhibited reduced F-actin polymerization a...
Scientific reports, Dec 15, 2016
Although plasminogen is a key protein in fibrinolysis and several mutations in the plasminogen ge... more Although plasminogen is a key protein in fibrinolysis and several mutations in the plasminogen gene (PLG) have been identified that result in plasminogen deficiency, there are conflicting reports to associate it with the risk of thrombosis. Our aim was to unravel the genetic architecture of PLG in families with plasminogen deficiency and its relationship with spontaneous thrombotic events in these families. A total of 13 individuals from 4 families were recruited. Their genetic risk profile of thromboembolism was characterized using the Thrombo inCode kit. Only one family presented genetic risk of thromboembolism (homozygous carrier of F12 rs1801020 and F13A1 rs5985). The whole PLG was tested using Next Generation Sequencing (NGS) and 5 putative pathogenic mutations were found (after in silico predictions) and associated with plasminogen deficiency. Although we can not find genetic risk factors of thrombosis in 3 of 4 families, even the mutations associated with plasminogen deficien...
Rev Inst Adolfo Lutz, Dec 1, 1998
Investigación clínica, 2012
Abstract. Chronic Granulomatous Disease (CGD) is a primary immunodeficiency characterized by defe... more Abstract. Chronic Granulomatous Disease (CGD) is a primary immunodeficiency characterized by defects in superoxide (O2-) production, which result from mutations in one of the four NADPH oxidase components, predisposing to bacterial and fungal infections. Besides the O2-defect, it has been described that neutrophils from CGD patients are resistant to cell death, a phenomenon that has been connected to chronic inflammation and predisposition to autoimmune diseases. A diminished expression of Fas and its counterpart FasL, molecules known to play a major role in cell death, has been described in lymphocytes depleted of O2-reactive oxygen species (ROS), suggesting an involvement of ROS in Fas/FasL expression. In this work, Fas and FasL expressions were analyzed in T cells and neutrophils from two CGD families, previously known to harbor two different molecular defects: absence of either p47-phox or p67-phox. We found that T lymphocytes from CGD patients express low levels of Fas and FasL...
Thrombosis and Haemostasis, 2005
SummaryIndirect molecular diagnosis of hemophilia A (HA) is carried out by analyzing intragenic p... more SummaryIndirect molecular diagnosis of hemophilia A (HA) is carried out by analyzing intragenic polymorphic markers described along the coagulation factorVIII (FVIII) gene. Several studies have demonstrated that the two commonly used intronic short tandem repeats (STR13 and STR22) located in the FVIII gene are highly informative for this task. Two extragenic markers closely linked to FVIII (DXS1073 and DXS1108) have also been described as valuable tools for gene tracking. The objective of the present work was to develop a rapid, single-tube automated method to simultaneously analyze these four STRs. Consistent amplification was achieved by quadruplex fluorescent PCR and the products were analyzed by capillary electrophoresis. Validation of the method included DNA analysis of 88 individuals from a control population, 45 HA patients and 32 individuals from 10 HA-affected families. Statistical study showed that the STR13, STR22 and DXS1108 loci were in significant linkage disequilibriu...
Revista de Biología Tropical, 2013
Paternal behavior and testosterone plasma levels in the Volcano Mouse Neotomodon alstoni (Rodenti... more Paternal behavior and testosterone plasma levels in the Volcano Mouse Neotomodon alstoni (Rodentia: Muridae). Although initially it was thought that testosterone inhibited the display of paternal behavior in males of rodents, it has been shown that in some species high testosterone levels are needed for exhibition of paternal care. In captivity, males of volcano Mouse (Neotomodon alstoni) provide pups the same care provided by the mother, with the exception of suckling. Here we measured plasmatic testosterone concentrations 10 days after mating, five and 20 days postpartum, and 10 days after males were isolated from their families in order to determine possible changes in this hormone, associated to the presence and age of pups. Males of volcano Mouse exhibited paternal behavior when their testosterone levels were relatively high. Although levels of this hormone did not change with the presence or pups age, males that invested more time in huddling showed higher testosterone levels. It is possible that in the volcano Mouse testosterone modulates paternal behavior indirectly, as in the California mouse.
Thrombosis and Haemostasis, 2009
SummaryMolecular diagnosis of von Willebrand Disease (VWD) is particularly complex. The autosomal... more SummaryMolecular diagnosis of von Willebrand Disease (VWD) is particularly complex. The autosomal von Willebrand factor gene (VWF) is large and highly polymorphic, and there is a highly homologous (>96%) partial pseudogene in chromosome 22. Because of these difficulties, application of molecular study of VWD to the clinical routine has been considerably delayed. Recent advances in sequencing technology and bioinformatics could convert direct sequencing of the complete VWF into a routine diagnostic tool for VWD, which is especially desirable in types 1 and 3. This study describes a highly optimized procedure in which all the coding and intronic flanking regions of VWF are amplified under identical thermocycling parameters in a ready-to-use PCR plate format. The entire sequencing procedure, from blood extraction to mutation identification, can be done within 24 hours, resulting in a simple, versatile, cost-effective strategy with little hands-on time requirements. To validate the m...
Journal of Thrombosis and Haemostasis, 2010
![Research paper thumbnail of Pyrano[3,2-c]quinoline−6-Chlorotacrine Hybrids as a Novel Family of Acetylcholinesterase- and β-Amyloid-Directed Anti-Alzheimer Compounds](https://attachments.academia-assets.com/94352844/thumbnails/1.jpg)
](Journal of Medicinal Chemistry, 2009
Two isomeric series of dual binding site acetylcholinesterase (AChE) inhibitors have been designe... more Two isomeric series of dual binding site acetylcholinesterase (AChE) inhibitors have been designed, synthesized, and tested for their ability to inhibit AChE, butyrylcholinesterase, AChE-induced and selfinduced β-amyloid (Aβ) aggregation, and β-secretase (BACE-1) and to cross blood-brain barrier. The new hybrids consist of a unit of 6-chlorotacrine and a multicomponent reaction-derived pyrano[3,2-c]quinoline scaffold as the active-site and peripheral-site interacting moieties, respectively, connected through an oligomethylene linker containing an amido group at variable position. Indeed, molecular modeling and kinetic studies have confirmed the dual site binding of these compounds. The new hybrids, and particularly 27, retain the potent and selective human AChE inhibitory activity of the parent 6-chlorotacrine while exhibiting a significant in vitro inhibitory activity toward the AChE-induced and self-induced Aβ aggregation and toward BACE-1, as well as ability to enter the central nervous system, which makes them promising anti-Alzheimer lead compounds.
Proceedings of the 2nd World Congress on New Technologies, Jun 1, 2017
Problemas del Desarrollo. Revista Latinoamericana de Economía, 2009
Se analizan las organizaciones de productores de sorgo del estado de Guanajuato y el acceso de és... more Se analizan las organizaciones de productores de sorgo del estado de Guanajuato y el acceso de éstas a los programas de apoyo orientados a la comercialización del grano. Para ello, se aplicaron entrevistas abiertas a productores, a representantes de organizaciones y a funcionarios de los distintos niveles de gobierno. 89% de las organizaciones estudiadas tienen al menos catorce años de antigüedad, se integran en promedio con 62 productores y su actividad está orientada fundamentalmente a la comercialización de granos, la gestión de crédito y la captación de los apoyos federales para la comercialización. Se concluye que las organizaciones bajo estudio tienen dificultades para acceder a los apoyos a la comercialización, debido a que son pequeñas, con baja capacidad de almacenaje y de acceso limitado al financiamiento.
Environmental Science and Pollution Research, 2018
Metal contamination is a recurring problem in Peru, caused mainly by mine tailings from a past ac... more Metal contamination is a recurring problem in Peru, caused mainly by mine tailings from a past active mining activity. The Ancash region has the largest number of environmental liabilities, which mobilizes high levels of metals and acid drainages into soils and freshwater sources, posing a standing risk on human and environmental health. Native plant species spontaneously growing on naturally acidified soils and acid mine tailings show a unique tolerance to high metal concentrations and are thus potential candidates for soil phytoremediation. However, little is known about their propagation capacity and metal accumulation under controlled conditions. In this study, we aimed at characterizing nine native plant species, previously identified as potential hyperaccumulators, from areas impacted by mine tailings in the Ancash region. Plants were grown on mine soils under greenhouse conditions during 5 months, after which the concentration of Cd, Cu, Ni, Pb, and Zn was analyzed in roots, shoots, and soils. The bioaccumulation (BAF) and translocation factor (TF) were calculated to determine the amount of each metal accumulated in the roots and shoots and to identify which species could be better suited for phytoremediation purposes. Soil samples contained high Cd (6.50-49.80 mg/kg), Cu (159.50-1187.00 mg/kg), Ni (3.50-8.70 mg/kg), Pb (1707.00-4243.00 mg/kg), and Zn (909.00-7100.00 mg/kg) concentrations exceeding national environmental quality standards. After exposure to mine tailings, concentrations of metals in shoots were highest in
PloS one, 2018
In families at risk from monogenic diseases affected offspring, it is fundamental the development... more In families at risk from monogenic diseases affected offspring, it is fundamental the development of a suitable Double Factor Preimplantation Genetic Testing (DF-PGT) method for both single-gene analysis and chromosome complement screening. Aneuploidy is not only a major issue in advanced-maternal-age patients and balanced translocation carriers, but also the aneuploidy rate is extremely high in patients undergoing in vitro fertilization (IVF), even in young donors. To adequate NGS technology to the DF-PGT strategy four different whole genome amplification systems (Sureplex, MALBAC, and two multiple displacement amplification systems-MDA) were tested using TruSight One panel on cell lines and blastocyst trophectoderm biopsies-TE. Embryo cytogenetic status was analyzed by Nexus software. Sureplex and MALBAC DNA products were considered not suitable for PGT diagnosis due to inconsistent and poor results on Trusight one (TSO) panel. Results obtained with both MDA based methods (GEH-MDA...
Physical Therapy, 2003
Background and Purpose. Little research has been done regarding the attitudes and behaviors of ph... more Background and Purpose. Little research has been done regarding the attitudes and behaviors of physical therapists relative to the use of evidence in practice. The purposes of this study were to describe the beliefs, attitudes, knowledge, and behaviors of physical therapist members of the American Physical Therapy Association (APTA) as they relate to evidence-based practice (EBP) and to generate hypotheses about the relationship between these attributes and personal and practice characteristics of the respondents. Methods. A survey of a random sample of physical therapist members of APTA resulted in a 48.8% return rate and a sample of 488 that was fairly representative of the national membership. Participants completed a questionnaire designed to determine beliefs, attitudes, knowledge, and behaviors regarding EBP, as well as demographic information about themselves and their practice settings. Responses were summarized for each item, and logistic regression analyses were used to ex...
The American Journal of Tropical Medicine and Hygiene, 1998
We report a human immunodeficiency virus (HIV)-infected man with chronic Chagas' disease who deve... more We report a human immunodeficiency virus (HIV)-infected man with chronic Chagas' disease who developed a congestive heart failure that could not be clinically controlled. Endomyocardial biopsy revealed severe myocarditis and the xenodiagnosis result was positive, but Trypanosoma cruzi by direct microscopic examination of the blood was found only four months after the symptoms had started. Treatment with benznidazole was effective in reducing parasitemia, stabilizing the clinical status, and controlling tissue damage related to the parasite. Although the finding of T. cruzi trypomastigotes by direct microscopic examination of the blood has been considered the mark of Chagas' reactivation in immunocompromised patients with chronic disease, in this case it was a late finding.
PloS one, 2017
Venous thromboembolism is a complex disease with a high heritability. There are significant assoc... more Venous thromboembolism is a complex disease with a high heritability. There are significant associations among Factor XI (FXI) levels and SNPs in the KNG1 and F11 loci. Our aim was to identify the genetic variation of KNG1 and F11 that might account for the variability of FXI levels. The KNG1 and F11 loci were sequenced completely in 110 unrelated individuals from the GAIT-2 (Genetic Analysis of Idiopathic Thrombophilia 2) Project using Next Generation Sequencing on an Illumina MiSeq. The GAIT-2 Project is a study of 935 individuals in 35 extended Spanish families selected through a proband with idiopathic thrombophilia. Among the 110 individuals, a subset of 40 individuals was chosen as a discovery sample for identifying variants. A total of 762 genetic variants were detected. Several significant associations were established among common variants and low-frequency variants sets in KNG1 and F11 with FXI levels using the PLINK and SKAT packages. Among these associations, those of rs...
PloS one, 2017
Hepatocyte poliploidization is an age-dependent process, being cytokinesis failure the main mecha... more Hepatocyte poliploidization is an age-dependent process, being cytokinesis failure the main mechanism of polyploid hepatocyte formation. Our aim was to study the role of p38α MAPK in the regulation of actin cytoskeleton and cytokinesis in hepatocytes during development and aging. Wild type and p38α liver-specific knock out mice at different ages (after weaning, adults and old) were used. We show that p38α MAPK deficiency induces actin disassembly upon aging and also cytokinesis failure leading to enhanced binucleation. Although the steady state levels of cyclin D1 in wild type and p38α knock out old livers remained unaffected, cyclin B1- a marker for G2/M transition- was significantly overexpressed in p38α knock out mice. Our findings suggest that hepatocytes do enter into S phase but they do not complete cell division upon p38α deficiency leading to cytokinesis failure and binucleation. Moreover, old liver-specific p38α MAPK knock out mice exhibited reduced F-actin polymerization a...
Scientific reports, Dec 15, 2016
Although plasminogen is a key protein in fibrinolysis and several mutations in the plasminogen ge... more Although plasminogen is a key protein in fibrinolysis and several mutations in the plasminogen gene (PLG) have been identified that result in plasminogen deficiency, there are conflicting reports to associate it with the risk of thrombosis. Our aim was to unravel the genetic architecture of PLG in families with plasminogen deficiency and its relationship with spontaneous thrombotic events in these families. A total of 13 individuals from 4 families were recruited. Their genetic risk profile of thromboembolism was characterized using the Thrombo inCode kit. Only one family presented genetic risk of thromboembolism (homozygous carrier of F12 rs1801020 and F13A1 rs5985). The whole PLG was tested using Next Generation Sequencing (NGS) and 5 putative pathogenic mutations were found (after in silico predictions) and associated with plasminogen deficiency. Although we can not find genetic risk factors of thrombosis in 3 of 4 families, even the mutations associated with plasminogen deficien...
Rev Inst Adolfo Lutz, Dec 1, 1998
Investigación clínica, 2012
Abstract. Chronic Granulomatous Disease (CGD) is a primary immunodeficiency characterized by defe... more Abstract. Chronic Granulomatous Disease (CGD) is a primary immunodeficiency characterized by defects in superoxide (O2-) production, which result from mutations in one of the four NADPH oxidase components, predisposing to bacterial and fungal infections. Besides the O2-defect, it has been described that neutrophils from CGD patients are resistant to cell death, a phenomenon that has been connected to chronic inflammation and predisposition to autoimmune diseases. A diminished expression of Fas and its counterpart FasL, molecules known to play a major role in cell death, has been described in lymphocytes depleted of O2-reactive oxygen species (ROS), suggesting an involvement of ROS in Fas/FasL expression. In this work, Fas and FasL expressions were analyzed in T cells and neutrophils from two CGD families, previously known to harbor two different molecular defects: absence of either p47-phox or p67-phox. We found that T lymphocytes from CGD patients express low levels of Fas and FasL...
Thrombosis and Haemostasis, 2005
SummaryIndirect molecular diagnosis of hemophilia A (HA) is carried out by analyzing intragenic p... more SummaryIndirect molecular diagnosis of hemophilia A (HA) is carried out by analyzing intragenic polymorphic markers described along the coagulation factorVIII (FVIII) gene. Several studies have demonstrated that the two commonly used intronic short tandem repeats (STR13 and STR22) located in the FVIII gene are highly informative for this task. Two extragenic markers closely linked to FVIII (DXS1073 and DXS1108) have also been described as valuable tools for gene tracking. The objective of the present work was to develop a rapid, single-tube automated method to simultaneously analyze these four STRs. Consistent amplification was achieved by quadruplex fluorescent PCR and the products were analyzed by capillary electrophoresis. Validation of the method included DNA analysis of 88 individuals from a control population, 45 HA patients and 32 individuals from 10 HA-affected families. Statistical study showed that the STR13, STR22 and DXS1108 loci were in significant linkage disequilibriu...
Revista de Biología Tropical, 2013
Paternal behavior and testosterone plasma levels in the Volcano Mouse Neotomodon alstoni (Rodenti... more Paternal behavior and testosterone plasma levels in the Volcano Mouse Neotomodon alstoni (Rodentia: Muridae). Although initially it was thought that testosterone inhibited the display of paternal behavior in males of rodents, it has been shown that in some species high testosterone levels are needed for exhibition of paternal care. In captivity, males of volcano Mouse (Neotomodon alstoni) provide pups the same care provided by the mother, with the exception of suckling. Here we measured plasmatic testosterone concentrations 10 days after mating, five and 20 days postpartum, and 10 days after males were isolated from their families in order to determine possible changes in this hormone, associated to the presence and age of pups. Males of volcano Mouse exhibited paternal behavior when their testosterone levels were relatively high. Although levels of this hormone did not change with the presence or pups age, males that invested more time in huddling showed higher testosterone levels. It is possible that in the volcano Mouse testosterone modulates paternal behavior indirectly, as in the California mouse.
Thrombosis and Haemostasis, 2009
SummaryMolecular diagnosis of von Willebrand Disease (VWD) is particularly complex. The autosomal... more SummaryMolecular diagnosis of von Willebrand Disease (VWD) is particularly complex. The autosomal von Willebrand factor gene (VWF) is large and highly polymorphic, and there is a highly homologous (>96%) partial pseudogene in chromosome 22. Because of these difficulties, application of molecular study of VWD to the clinical routine has been considerably delayed. Recent advances in sequencing technology and bioinformatics could convert direct sequencing of the complete VWF into a routine diagnostic tool for VWD, which is especially desirable in types 1 and 3. This study describes a highly optimized procedure in which all the coding and intronic flanking regions of VWF are amplified under identical thermocycling parameters in a ready-to-use PCR plate format. The entire sequencing procedure, from blood extraction to mutation identification, can be done within 24 hours, resulting in a simple, versatile, cost-effective strategy with little hands-on time requirements. To validate the m...
Journal of Thrombosis and Haemostasis, 2010
Journal of Medicinal Chemistry, 2009
Two isomeric series of dual binding site acetylcholinesterase (AChE) inhibitors have been designe... more Two isomeric series of dual binding site acetylcholinesterase (AChE) inhibitors have been designed, synthesized, and tested for their ability to inhibit AChE, butyrylcholinesterase, AChE-induced and selfinduced β-amyloid (Aβ) aggregation, and β-secretase (BACE-1) and to cross blood-brain barrier. The new hybrids consist of a unit of 6-chlorotacrine and a multicomponent reaction-derived pyrano[3,2-c]quinoline scaffold as the active-site and peripheral-site interacting moieties, respectively, connected through an oligomethylene linker containing an amido group at variable position. Indeed, molecular modeling and kinetic studies have confirmed the dual site binding of these compounds. The new hybrids, and particularly 27, retain the potent and selective human AChE inhibitory activity of the parent 6-chlorotacrine while exhibiting a significant in vitro inhibitory activity toward the AChE-induced and self-induced Aβ aggregation and toward BACE-1, as well as ability to enter the central nervous system, which makes them promising anti-Alzheimer lead compounds.