Borna disease virus (BDV) is an enveloped virus. Its non-segmented, negative-stranded RNA genome ... more Borna disease virus (BDV) is an enveloped virus. Its non-segmented, negative-stranded RNA genome has the coding capability for six main polypeptides and has an organization characteristic of members of the order Mononegavirales. However, based on its unique genetics and biological features, BDV is considered to be the prototypic member of a new virus family, Bornaviridae.
Background—It is unclear whether atrial fibrillation (AF) drivers in humans are focal or reentran... more Background—It is unclear whether atrial fibrillation (AF) drivers in humans are focal or reentrant. To test the hypothesis that functional reentry is involved in human AF maintenance, we determined the effects of adenosine infusion on local dominant frequency (DF) at different atrial sites. By increasing inward rectifier potassium channel conductance, adenosine would increase DF of reentrant drivers but decrease it
Anthrax lethal toxin is one of the fundamental components believed to be responsible for the viru... more Anthrax lethal toxin is one of the fundamental components believed to be responsible for the virulence of Bacillus anthracis. In order to find novel compounds with anti-lethal toxin properties, we used a cell-based assay to screen a collection of approximately 500 small molecules. Nineteen compounds that blocked lethal toxin-mediated killing of RAW 264.7 macrophages were identified, and we report here on the characterization of the two most potent antitoxic compounds, amiodarone and bepridil. These drugs are used to treat cardiac arrhythmia or angina in humans at doses similar to those that provide protection against lethal toxin in vitro. Our results support a model whereby the antitoxic properties of both drugs result from their ability to block endosomal acidification, thereby blocking toxin entry. Amiodarone was tested in vivo and found to significantly increase survival of lethal toxin-challenged Fischer rats.
SUMMARY.—Seasonal and interannual variability in laying date, clutch size, egg volume and hatchin... more SUMMARY.—Seasonal and interannual variability in laying date, clutch size, egg volume and hatching asynchrony of four lark species in Mediterranean Spain Aims: To describe the variation in laying date, clutch size, egg volume and hatching asynchrony of four lark species (Skylark Alauda arvensis, Short-toed Lark Calandrella brachydactyla, Thekla Lark Galerida theklae and Lesser Short-toed Lark Calandrella rufescens) and at two
Anal fissure is a split in the anoderm of the distal anal canal, characterized by severe anal pai... more Anal fissure is a split in the anoderm of the distal anal canal, characterized by severe anal pain on defecation and anal bleeding. Anal fissure is caused by a tear of the anoderm secondary to local ischemia associated to spasm of the internal anal sphincter. Treatments such as surgical or chemical sphincterotomy are effective, as overcoming spasm improves blood supply to the ischemic ulcer, leading to relief of symptoms and healing in the majority of cases.
Supplementary Material Available: Spectral data ('H NMR, 13C NMR, IR, MS), elemental analyses, an... more Supplementary Material Available: Spectral data ('H NMR, 13C NMR, IR, MS), elemental analyses, and melting points for la-e, 2a, 3b-e, 4b-e, and 6b-e and NOSEY spectra of 3d and 6d (7 pages). Ordering information is given on any current masthead page. CDC13) 6 0.51 (d, 3 H, J = 6.9 Hz), 2.05-2.15 (m, 1 H), 2.60-3.40 (br s, 2 H), 3.79 ( s , 6 H), 4.44 (d, 2 H, J = 9.8 Hz), 6.85-7.20 (m, 8 H).
... 15,16 In the presence of β-CD the azonium and amonium tautomers may be included (Scheme 3), a... more ... 15,16 In the presence of β-CD the azonium and amonium tautomers may be included (Scheme 3), and it was shown that the inclusion shifts the ... The fact that the reactions of 4−6 are not affected by cyclodextrin can be attributed to the presence of an organic cosolvent since it is ...
During the past decades, intense attention has been focused on the anti-tumor properties of marin... more During the past decades, intense attention has been focused on the anti-tumor properties of marine compounds which some of them have been revealed as potent apoptotic inducers. In the present work, we studied the mechanism of action of a new compound, Spisulosine (ES-285), isolated from the sea mollusc Spisula polynyma, in the prostate tumor PC-3 and LNCaP cell lines. Spisulosine inhibited cell proliferation with an IC50 of 1 microM in both cell lines, although it was more effective in the androgen-independent PC-3 cells. The anti-proliferative effect induced by Spisulosine in prostate cells was independent of peroxisome proliferator activated receptor gamma (PPARgamma) and phosphatidylinositol 3-kinase/(PI3K/Akt), Jun N-terminal kinase (JNK), p38 or classical protein kinase C (PKCs) pathways, as it was inferred from the results obtained with specific inhibitors of these routes. However, Spisulosine treatment of prostate cells induced an increase in the intracellular ceramide levels...
The molecular bases of self-incompatibility have been intensively studied in a restricted number ... more The molecular bases of self-incompatibility have been intensively studied in a restricted number of model species, but for most families the expression and distribution of S-proteins is unknown. In this work, pistil cryosections from apple were used for in situ detection of S-proteins. Two specific antibodies, one against the S3-protein and another against all apple S-proteins were used. S-proteins were shown to be localised in the intercellular space of the transmitting tissue, both in the stigma and style, which agrees with the proposed mechanism of action for S-RNases in gametophytic self-incompatibility. Some intracellular labelling was also observed in all ovary sections, confined to one layer of the nucellus surrounding the embryo sac, but this labelling was found to be non-S-allele-specific. Nevertheless, the signal in the ovary was tissue-specific, which may indicate that some component not encoded by the S-locus but similar to S-proteins was detected. To the best of our knowledge this is the first report on the precise distribution of S-RNases in a rosaceous species.
It is important to assess the potential efficacy and safety of offering donation incentives as pa... more It is important to assess the potential efficacy and safety of offering donation incentives as part of recruitment and retention programs. In 1995, 7489 allogeneic donors responded to an anonymous mail survey that inquired about demographics, donation history, infectious disease risks, and the potential appeal of incentives. The projected net effect of offering blood credits and medical testing would be to motivate, respectively, 58 percent and 46 percent of donors to return, whereas offering an item of limited value would motivate 20 percent to do so. First-time and younger donors reported more frequently than repeat or older donors that incentives would appeal to them. Donors attracted by cash were 60 percent more likely to have a risk for transfusion-transmissible infections (p = 0.03). Although not statistically significant, the odds of being an at-risk donor were higher among individuals attracted by tickets to events (OR 1.5) and extra time off work (OR 1.2). These findings suggest that offering blood credits and (though to a lesser extent) items of limited value could be safe and effective strategies for retaining donors. Although medical tests were found to have broad appeal, studies are needed to identify tests in which donors would be most interested.
We document a helper-independent reverse genetics system for rescuing infectious arenaviruses fro... more We document a helper-independent reverse genetics system for rescuing infectious arenaviruses from cloned cDNAs. We constructed plasmids containing full-length cDNAs of the antigenomic (ag) L and S segments of the Armstrong (ARM) strain of the prototypic Arenavirus lymphocytic choriomeningitis virus (LCMV) flanked at their 5′-and 3′-termini by the T7 RNA polymerase (T7RP) promoter and ribozyme sequences, respectively. These plasmids directed intracellular synthesis of viral L and S ag RNA species in cells expressing plasmid-supplied T7RP. Coexpression of plasmid-supplied LCMV trans-acting factors, nucleoprotein (NP) and polymerase (L), resulted in replication and expression of L and S ag and genome RNA species, and generation of LCMV infectious progeny termed rT7/LCMV. The recombinant rT7/LCMV was unequivocally identified based on a genetic tag introduced in the recombinant S segment. In addition, rT7/LCMV exhibited growth and biological properties predicted for an ARM-like LCMV. To our knowledge, this is the first documented Arenavirus rescue, as well as of an ambisense negative strand (NS) RNA virus, entirely from cloned cDNAs. Our results extend the use of reverse genetic approaches for DNA-mediated virus rescue to all known virus families with NS RNA genome.
There is a declining margin between US blood collections and transfusions. Donation patterns were... more There is a declining margin between US blood collections and transfusions. Donation patterns were examined to characterize returning first-time donors and predict the impact on blood availability of decreasing the number of nonreturning donors. First-time donors giving between 1991 and 1994 were followed for 3 to 6 years. The impact of decreasing the number of nonreturning donors in a 12-month period was projected using the Poisson distribution to model the donation patterns of 539,063 donors who gave in 1995. Repeat donors were classified as "returning first-time" (gave a first-time donation within 12 months of their index donation), "established" (gave a repeat donation), and…
Chemotherapy has been associated with premature ovarian failure and infertility in women with can... more Chemotherapy has been associated with premature ovarian failure and infertility in women with cancer. It is well known that anticancer drugs reduce the primordial follicle pool and harm the ovarian blood vascularization leading to ovarian atrophy. However, their mechanism of injury still remains unclear.
The successful establishment of angiosperms on land is in part determined by their floral design.... more The successful establishment of angiosperms on land is in part determined by their floral design. Because plants cannot move to find the ideal mate, they have developed a great variety of flowers to provide different mechanisms of pollen release, pollen transfer, and ...
The human cell line U937 differentiates to monocyte macrophage-like cells in response to tumour-p... more The human cell line U937 differentiates to monocyte macrophage-like cells in response to tumour-promoting phorbol esters. This effect is attributed to activation of protein kinase C. We show here that U937 cell differentiation induced by 12-0-tetradecanoylphorbol 13-acetate (TPA) is associated with cytoplasmic alkalinization. Ethyl-isopropyl-amiloride (EIPA), a potent inhibitor of N a + / H + exchange, blocked both cytoplasmic alkalinization and cell differentiation. Cell acidification by addition of 2 -4 mM sodium propionate also blocked TPAinduced U937 cell differentiation. These results suggest that a sustained cell alkalinization mediated by activation of N a + / H t exchange is essential for TPA-induced differentiation in U937 cells. The increase of cytoplasmic free calcium concentration ([Ca' 'Ii) by addition of the calcium ionophore ionomycin enhanced TPA-induced alkalinization by increasing the apparent affinity of the Na+/H+ antiporter for intracellular H + . Treatment with ionornycin also potentiated differentiation of U937 cells induced by TPA. This synergism suggests that [Ca2+Ii either potentiates the activation of protein kinase C or triggers additional transducing mechanisms. The key events of this interaction occur during the first 30 min of treatment, even though cell differentiation manifests much later.
Borna disease virus (BDV) is an enveloped virus. Its non-segmented, negative-stranded RNA genome ... more Borna disease virus (BDV) is an enveloped virus. Its non-segmented, negative-stranded RNA genome has the coding capability for six main polypeptides and has an organization characteristic of members of the order Mononegavirales. However, based on its unique genetics and biological features, BDV is considered to be the prototypic member of a new virus family, Bornaviridae.
Background—It is unclear whether atrial fibrillation (AF) drivers in humans are focal or reentran... more Background—It is unclear whether atrial fibrillation (AF) drivers in humans are focal or reentrant. To test the hypothesis that functional reentry is involved in human AF maintenance, we determined the effects of adenosine infusion on local dominant frequency (DF) at different atrial sites. By increasing inward rectifier potassium channel conductance, adenosine would increase DF of reentrant drivers but decrease it
Anthrax lethal toxin is one of the fundamental components believed to be responsible for the viru... more Anthrax lethal toxin is one of the fundamental components believed to be responsible for the virulence of Bacillus anthracis. In order to find novel compounds with anti-lethal toxin properties, we used a cell-based assay to screen a collection of approximately 500 small molecules. Nineteen compounds that blocked lethal toxin-mediated killing of RAW 264.7 macrophages were identified, and we report here on the characterization of the two most potent antitoxic compounds, amiodarone and bepridil. These drugs are used to treat cardiac arrhythmia or angina in humans at doses similar to those that provide protection against lethal toxin in vitro. Our results support a model whereby the antitoxic properties of both drugs result from their ability to block endosomal acidification, thereby blocking toxin entry. Amiodarone was tested in vivo and found to significantly increase survival of lethal toxin-challenged Fischer rats.
SUMMARY.—Seasonal and interannual variability in laying date, clutch size, egg volume and hatchin... more SUMMARY.—Seasonal and interannual variability in laying date, clutch size, egg volume and hatching asynchrony of four lark species in Mediterranean Spain Aims: To describe the variation in laying date, clutch size, egg volume and hatching asynchrony of four lark species (Skylark Alauda arvensis, Short-toed Lark Calandrella brachydactyla, Thekla Lark Galerida theklae and Lesser Short-toed Lark Calandrella rufescens) and at two
Anal fissure is a split in the anoderm of the distal anal canal, characterized by severe anal pai... more Anal fissure is a split in the anoderm of the distal anal canal, characterized by severe anal pain on defecation and anal bleeding. Anal fissure is caused by a tear of the anoderm secondary to local ischemia associated to spasm of the internal anal sphincter. Treatments such as surgical or chemical sphincterotomy are effective, as overcoming spasm improves blood supply to the ischemic ulcer, leading to relief of symptoms and healing in the majority of cases.
Supplementary Material Available: Spectral data ('H NMR, 13C NMR, IR, MS), elemental analyses, an... more Supplementary Material Available: Spectral data ('H NMR, 13C NMR, IR, MS), elemental analyses, and melting points for la-e, 2a, 3b-e, 4b-e, and 6b-e and NOSEY spectra of 3d and 6d (7 pages). Ordering information is given on any current masthead page. CDC13) 6 0.51 (d, 3 H, J = 6.9 Hz), 2.05-2.15 (m, 1 H), 2.60-3.40 (br s, 2 H), 3.79 ( s , 6 H), 4.44 (d, 2 H, J = 9.8 Hz), 6.85-7.20 (m, 8 H).
... 15,16 In the presence of β-CD the azonium and amonium tautomers may be included (Scheme 3), a... more ... 15,16 In the presence of β-CD the azonium and amonium tautomers may be included (Scheme 3), and it was shown that the inclusion shifts the ... The fact that the reactions of 4−6 are not affected by cyclodextrin can be attributed to the presence of an organic cosolvent since it is ...
During the past decades, intense attention has been focused on the anti-tumor properties of marin... more During the past decades, intense attention has been focused on the anti-tumor properties of marine compounds which some of them have been revealed as potent apoptotic inducers. In the present work, we studied the mechanism of action of a new compound, Spisulosine (ES-285), isolated from the sea mollusc Spisula polynyma, in the prostate tumor PC-3 and LNCaP cell lines. Spisulosine inhibited cell proliferation with an IC50 of 1 microM in both cell lines, although it was more effective in the androgen-independent PC-3 cells. The anti-proliferative effect induced by Spisulosine in prostate cells was independent of peroxisome proliferator activated receptor gamma (PPARgamma) and phosphatidylinositol 3-kinase/(PI3K/Akt), Jun N-terminal kinase (JNK), p38 or classical protein kinase C (PKCs) pathways, as it was inferred from the results obtained with specific inhibitors of these routes. However, Spisulosine treatment of prostate cells induced an increase in the intracellular ceramide levels...
The molecular bases of self-incompatibility have been intensively studied in a restricted number ... more The molecular bases of self-incompatibility have been intensively studied in a restricted number of model species, but for most families the expression and distribution of S-proteins is unknown. In this work, pistil cryosections from apple were used for in situ detection of S-proteins. Two specific antibodies, one against the S3-protein and another against all apple S-proteins were used. S-proteins were shown to be localised in the intercellular space of the transmitting tissue, both in the stigma and style, which agrees with the proposed mechanism of action for S-RNases in gametophytic self-incompatibility. Some intracellular labelling was also observed in all ovary sections, confined to one layer of the nucellus surrounding the embryo sac, but this labelling was found to be non-S-allele-specific. Nevertheless, the signal in the ovary was tissue-specific, which may indicate that some component not encoded by the S-locus but similar to S-proteins was detected. To the best of our knowledge this is the first report on the precise distribution of S-RNases in a rosaceous species.
It is important to assess the potential efficacy and safety of offering donation incentives as pa... more It is important to assess the potential efficacy and safety of offering donation incentives as part of recruitment and retention programs. In 1995, 7489 allogeneic donors responded to an anonymous mail survey that inquired about demographics, donation history, infectious disease risks, and the potential appeal of incentives. The projected net effect of offering blood credits and medical testing would be to motivate, respectively, 58 percent and 46 percent of donors to return, whereas offering an item of limited value would motivate 20 percent to do so. First-time and younger donors reported more frequently than repeat or older donors that incentives would appeal to them. Donors attracted by cash were 60 percent more likely to have a risk for transfusion-transmissible infections (p = 0.03). Although not statistically significant, the odds of being an at-risk donor were higher among individuals attracted by tickets to events (OR 1.5) and extra time off work (OR 1.2). These findings suggest that offering blood credits and (though to a lesser extent) items of limited value could be safe and effective strategies for retaining donors. Although medical tests were found to have broad appeal, studies are needed to identify tests in which donors would be most interested.
We document a helper-independent reverse genetics system for rescuing infectious arenaviruses fro... more We document a helper-independent reverse genetics system for rescuing infectious arenaviruses from cloned cDNAs. We constructed plasmids containing full-length cDNAs of the antigenomic (ag) L and S segments of the Armstrong (ARM) strain of the prototypic Arenavirus lymphocytic choriomeningitis virus (LCMV) flanked at their 5′-and 3′-termini by the T7 RNA polymerase (T7RP) promoter and ribozyme sequences, respectively. These plasmids directed intracellular synthesis of viral L and S ag RNA species in cells expressing plasmid-supplied T7RP. Coexpression of plasmid-supplied LCMV trans-acting factors, nucleoprotein (NP) and polymerase (L), resulted in replication and expression of L and S ag and genome RNA species, and generation of LCMV infectious progeny termed rT7/LCMV. The recombinant rT7/LCMV was unequivocally identified based on a genetic tag introduced in the recombinant S segment. In addition, rT7/LCMV exhibited growth and biological properties predicted for an ARM-like LCMV. To our knowledge, this is the first documented Arenavirus rescue, as well as of an ambisense negative strand (NS) RNA virus, entirely from cloned cDNAs. Our results extend the use of reverse genetic approaches for DNA-mediated virus rescue to all known virus families with NS RNA genome.
There is a declining margin between US blood collections and transfusions. Donation patterns were... more There is a declining margin between US blood collections and transfusions. Donation patterns were examined to characterize returning first-time donors and predict the impact on blood availability of decreasing the number of nonreturning donors. First-time donors giving between 1991 and 1994 were followed for 3 to 6 years. The impact of decreasing the number of nonreturning donors in a 12-month period was projected using the Poisson distribution to model the donation patterns of 539,063 donors who gave in 1995. Repeat donors were classified as "returning first-time" (gave a first-time donation within 12 months of their index donation), "established" (gave a repeat donation), and…
Chemotherapy has been associated with premature ovarian failure and infertility in women with can... more Chemotherapy has been associated with premature ovarian failure and infertility in women with cancer. It is well known that anticancer drugs reduce the primordial follicle pool and harm the ovarian blood vascularization leading to ovarian atrophy. However, their mechanism of injury still remains unclear.
The successful establishment of angiosperms on land is in part determined by their floral design.... more The successful establishment of angiosperms on land is in part determined by their floral design. Because plants cannot move to find the ideal mate, they have developed a great variety of flowers to provide different mechanisms of pollen release, pollen transfer, and ...
The human cell line U937 differentiates to monocyte macrophage-like cells in response to tumour-p... more The human cell line U937 differentiates to monocyte macrophage-like cells in response to tumour-promoting phorbol esters. This effect is attributed to activation of protein kinase C. We show here that U937 cell differentiation induced by 12-0-tetradecanoylphorbol 13-acetate (TPA) is associated with cytoplasmic alkalinization. Ethyl-isopropyl-amiloride (EIPA), a potent inhibitor of N a + / H + exchange, blocked both cytoplasmic alkalinization and cell differentiation. Cell acidification by addition of 2 -4 mM sodium propionate also blocked TPAinduced U937 cell differentiation. These results suggest that a sustained cell alkalinization mediated by activation of N a + / H t exchange is essential for TPA-induced differentiation in U937 cells. The increase of cytoplasmic free calcium concentration ([Ca' 'Ii) by addition of the calcium ionophore ionomycin enhanced TPA-induced alkalinization by increasing the apparent affinity of the Na+/H+ antiporter for intracellular H + . Treatment with ionornycin also potentiated differentiation of U937 cells induced by TPA. This synergism suggests that [Ca2+Ii either potentiates the activation of protein kinase C or triggers additional transducing mechanisms. The key events of this interaction occur during the first 30 min of treatment, even though cell differentiation manifests much later.
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Papers by ana sanchez