Paul Ledesma - Academia.edu (original) (raw)

Papers by Paul Ledesma

PLOS One, 2009

Consensus exists that lipids must play key functions in synaptic activity but precise mechanistic... more Consensus exists that lipids must play key functions in synaptic activity but precise mechanistic information is limited. Acid sphingomyelinase knockout mice (ASMko) are a suitable model to address the role of sphingolipids in synaptic regulation as they recapitulate a mental retardation syndrome, Niemann Pick disease type A (NPA), and their neurons have altered levels of sphingomyelin (SM) and its derivatives. Electrophysiological recordings showed that ASMko hippocampi have increased paired-pulse facilitation and post-tetanic potentiation. Consistently, electron microscopy revealed reduced number of docked vesicles. Biochemical analysis of ASMko synaptic membranes unveiled higher amounts of SM and sphingosine (Se) and enhanced interaction of the docking molecules Munc18 and syntaxin1. In vitro reconstitution assays demonstrated that Se changes syntaxin1 conformation enhancing its interaction with Munc18. Moreover, Se reduces vesicle docking in primary neurons and increases paired-pulse facilitation when added to wt hippocampal slices. These data provide with a novel mechanism for synaptic vesicle control by sphingolipids and could explain cognitive deficits of NPA patients.

International Journal of Antimicrobial Agents, 2007

Cancer, 1984

From April 1975 to January 1982, 97 patients with greater than or equal to 50% of the liver invol... more From April 1975 to January 1982, 97 patients with greater than or equal to 50% of the liver involved with metastasis from colorectal carcinoma underwent hepatic artery ligation. The purpose was to evaluate median survival times in relation to performance status, synchronous intraabdominal metastasis, pulmonary metastasis, liver function tests (alkaline phosphatase, serum glutamic oxaloacetic transaminase (SGOT), lactate dehydrogenase (LDH), total bilirubin, and Dukes' staging. Results reveal that for performance status 0 to 1 (normal or symptoms, but ambulatory), median survival time was 12.3 months; status 2 to 3 (in bed less than or greater than 50% of time), 8.3 months; status 4 (100% bedridden), 2.6 months, (P less than 0.01). Median survival time in patients with only intrahepatic metastasis was 10 months versus 7 months for synchronous intraabdominal metastasis (P less than 0.01). For 20 patients with pulmonary metastasis undergoing hepatic artery ligation, the median survival time was 8.8 months (P less than 0.05). The median survival time in patients whose alkaline phosphatase was 2 times normal was 12.4 months, whereas, if alkaline phosphatase was 2 times to 4 times or greater than 4 times normal, median survival times were 7.1 and 6.9 months, respectively (P less than 0.01). Factors that adversely affect survival for hepatic artery ligation are extrahepatic metastasis, poor performance status, and elevated liver function tests (alkaline phosphatase 2 times normal). The overall median survival time in this study is 9.5 months with certain subgroups achieving 12.4 months' survival.

Quaternary International

Cleaning works in the cave of Las Palomas in Teba (Málaga, Spain), developed by the Guadalteba Co... more Cleaning works in the cave of Las Palomas in Teba (Málaga, Spain), developed by the Guadalteba Consortium, have provided a number of lithic tools and knapping products that may be ascribed to the Mode III technotypological tradition as well as remains of a number of large mammal species typical of MiddleeLate Pleistocene times. Topographic measurements help to place this ancient cave within a karst landform. This discovery opens up new perspectives in the research on the Neanderthal groups that inhabited the valleys of Guadalteba and Turón rivers in the middle basin of the Guadalhorce River, and thus in the southern region of the Iberian Peninsula.

The understanding of the embryogenesis in living systems requires reliable quantitative analysis ... more The understanding of the embryogenesis in living systems requires reliable quantitative analysis of the cell migration throughout all the stages of development. This is a major challenge of the ”in-toto” reconstruction based on different modalities of ”in-vivo” imaging techniques-spatio-temporal resolution and image artifacts and noise. Several methods for cell tracking are available, but expensive manual interaction-time and human resources - is always required to enforce coherence. Because of this limitation it is necessary to restrict the experiments or assume an uncontrolled error rate. Is it possible to obtain automated reliable measurements of migration? can we provide a seed for biologists to complete cell lineages efficiently? We propose a filtering technique that considers trajectories as spatio-temporal connected structures that prunes out those that might introduce noise and false positives by using multi-dimensional morphological operators.

Antimicrobial Agents and Chemotherapy, 2008

Journal of Economic Studies, 2007

Purpose–The paper aims to re-examine the stationarity properties of unemployment rates in 12 Euro... more Purpose–The paper aims to re-examine the stationarity properties of unemployment rates in 12 European Union (EU) countries over the period 1988: I-1999: IV. Design/methodology/approach–This paper applies a battery of second-generation panel unit root tests that allow for cross-sectional correlation. Findings–The study shows that, contrary to previous empirical literature, hysteresis does not characterise EU unemployment. Originality/value–This paper uses recent advances in the econometrics of panel unit root tests. The new tests have ...

Abnormal protein processing and modification is associated with Alzheimer's disease (AD) patholog... more Abnormal protein processing and modification is associated with Alzheimer's disease (AD) pathology. The role of phosphorylation in AD has been studied extensively because the presumed abnormal phosphorylation of tau protein is believed to play a role in the formation of paired helical filaments. Glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) to serine and threonine residues is a dynamic protein modification of intracellular proteins, and it shares similar features with protein phosphorylation. In this study, O-GlcNAc glycosylation of proteins from autopsied human brains with confirmed AD and non-AD age-matched controls was examined.

The rapidly increasing data usage and overload in mobile broadband networks has driven mobile net... more The rapidly increasing data usage and overload in mobile broadband networks has driven mobile network providers to actively detect and bill customers who tether tablets and laptops to their mobile phone for mobile Internet access. However, users may not be willing to pay additional fees only because they use their bandwidth differently, and may consider tethering detection as violation of their privacy. Furthermore, accurate tethering detection is becoming harder for providers as many modern smartphones are under full control of the user, running customized, complex software and applications similar to desktop systems.

PLOS One, 2009

Consensus exists that lipids must play key functions in synaptic activity but precise mechanistic... more Consensus exists that lipids must play key functions in synaptic activity but precise mechanistic information is limited. Acid sphingomyelinase knockout mice (ASMko) are a suitable model to address the role of sphingolipids in synaptic regulation as they recapitulate a mental retardation syndrome, Niemann Pick disease type A (NPA), and their neurons have altered levels of sphingomyelin (SM) and its derivatives. Electrophysiological recordings showed that ASMko hippocampi have increased paired-pulse facilitation and post-tetanic potentiation. Consistently, electron microscopy revealed reduced number of docked vesicles. Biochemical analysis of ASMko synaptic membranes unveiled higher amounts of SM and sphingosine (Se) and enhanced interaction of the docking molecules Munc18 and syntaxin1. In vitro reconstitution assays demonstrated that Se changes syntaxin1 conformation enhancing its interaction with Munc18. Moreover, Se reduces vesicle docking in primary neurons and increases paired-pulse facilitation when added to wt hippocampal slices. These data provide with a novel mechanism for synaptic vesicle control by sphingolipids and could explain cognitive deficits of NPA patients.

International Journal of Antimicrobial Agents, 2007

Cancer, 1984

From April 1975 to January 1982, 97 patients with greater than or equal to 50% of the liver invol... more From April 1975 to January 1982, 97 patients with greater than or equal to 50% of the liver involved with metastasis from colorectal carcinoma underwent hepatic artery ligation. The purpose was to evaluate median survival times in relation to performance status, synchronous intraabdominal metastasis, pulmonary metastasis, liver function tests (alkaline phosphatase, serum glutamic oxaloacetic transaminase (SGOT), lactate dehydrogenase (LDH), total bilirubin, and Dukes' staging. Results reveal that for performance status 0 to 1 (normal or symptoms, but ambulatory), median survival time was 12.3 months; status 2 to 3 (in bed less than or greater than 50% of time), 8.3 months; status 4 (100% bedridden), 2.6 months, (P less than 0.01). Median survival time in patients with only intrahepatic metastasis was 10 months versus 7 months for synchronous intraabdominal metastasis (P less than 0.01). For 20 patients with pulmonary metastasis undergoing hepatic artery ligation, the median survival time was 8.8 months (P less than 0.05). The median survival time in patients whose alkaline phosphatase was 2 times normal was 12.4 months, whereas, if alkaline phosphatase was 2 times to 4 times or greater than 4 times normal, median survival times were 7.1 and 6.9 months, respectively (P less than 0.01). Factors that adversely affect survival for hepatic artery ligation are extrahepatic metastasis, poor performance status, and elevated liver function tests (alkaline phosphatase 2 times normal). The overall median survival time in this study is 9.5 months with certain subgroups achieving 12.4 months' survival.

Quaternary International

Cleaning works in the cave of Las Palomas in Teba (Málaga, Spain), developed by the Guadalteba Co... more Cleaning works in the cave of Las Palomas in Teba (Málaga, Spain), developed by the Guadalteba Consortium, have provided a number of lithic tools and knapping products that may be ascribed to the Mode III technotypological tradition as well as remains of a number of large mammal species typical of MiddleeLate Pleistocene times. Topographic measurements help to place this ancient cave within a karst landform. This discovery opens up new perspectives in the research on the Neanderthal groups that inhabited the valleys of Guadalteba and Turón rivers in the middle basin of the Guadalhorce River, and thus in the southern region of the Iberian Peninsula.

The understanding of the embryogenesis in living systems requires reliable quantitative analysis ... more The understanding of the embryogenesis in living systems requires reliable quantitative analysis of the cell migration throughout all the stages of development. This is a major challenge of the ”in-toto” reconstruction based on different modalities of ”in-vivo” imaging techniques-spatio-temporal resolution and image artifacts and noise. Several methods for cell tracking are available, but expensive manual interaction-time and human resources - is always required to enforce coherence. Because of this limitation it is necessary to restrict the experiments or assume an uncontrolled error rate. Is it possible to obtain automated reliable measurements of migration? can we provide a seed for biologists to complete cell lineages efficiently? We propose a filtering technique that considers trajectories as spatio-temporal connected structures that prunes out those that might introduce noise and false positives by using multi-dimensional morphological operators.

Antimicrobial Agents and Chemotherapy, 2008

Journal of Economic Studies, 2007

Purpose–The paper aims to re-examine the stationarity properties of unemployment rates in 12 Euro... more Purpose–The paper aims to re-examine the stationarity properties of unemployment rates in 12 European Union (EU) countries over the period 1988: I-1999: IV. Design/methodology/approach–This paper applies a battery of second-generation panel unit root tests that allow for cross-sectional correlation. Findings–The study shows that, contrary to previous empirical literature, hysteresis does not characterise EU unemployment. Originality/value–This paper uses recent advances in the econometrics of panel unit root tests. The new tests have ...

Abnormal protein processing and modification is associated with Alzheimer's disease (AD) patholog... more Abnormal protein processing and modification is associated with Alzheimer's disease (AD) pathology. The role of phosphorylation in AD has been studied extensively because the presumed abnormal phosphorylation of tau protein is believed to play a role in the formation of paired helical filaments. Glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) to serine and threonine residues is a dynamic protein modification of intracellular proteins, and it shares similar features with protein phosphorylation. In this study, O-GlcNAc glycosylation of proteins from autopsied human brains with confirmed AD and non-AD age-matched controls was examined.

The rapidly increasing data usage and overload in mobile broadband networks has driven mobile net... more The rapidly increasing data usage and overload in mobile broadband networks has driven mobile network providers to actively detect and bill customers who tether tablets and laptops to their mobile phone for mobile Internet access. However, users may not be willing to pay additional fees only because they use their bandwidth differently, and may consider tethering detection as violation of their privacy. Furthermore, accurate tethering detection is becoming harder for providers as many modern smartphones are under full control of the user, running customized, complex software and applications similar to desktop systems.