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Papers by jose manuel Hernandez
![Research paper thumbnail of Search for the Standard Model Higgs Boson Decaying to a bb[over ¯] Pair in Events with One Charged Lepton and Large Missing Transverse Energy Using the Full CDF Data Set](https://attachments.academia-assets.com/120242575/thumbnails/1.jpg)
](Physical Review Letters, 2012
Journal of Clinical Medicine, 2021
Background: Recent guidelines recommend establishing a local reference interval (RI) for thyroid ... more Background: Recent guidelines recommend establishing a local reference interval (RI) for thyroid function. We aimed to establish trimester-specific RIs for thyrotropin (TSH) and free thyroxine (FT4) in a cohort of healthy pregnant women in Catalonia (Spain). Methods: A prospective observational study was conducted with 332 healthy pregnant women, from the first trimester (1T) to delivery. TSH was measured using an Architect® immunoassay (Abbott) and FT4 by two immunoassays, Architect® (Abbott) and Cobas® (Roche), in the three trimesters. FT4 was also measured by liquid chromatography mass spectrometry (LC/MS/MS) in the 1T. Results: TSH (µUI/mL) increased throughout pregnancy (1T: 0.03–3.78; 2T: 0.51–3.53; 3T: 0.50–4.32; p < 0.0001) and FT4 (pmol/L) progressively decreased (Architect® 1T: 10.42–15.96; 2T: 8.37–12.74; 3T: 8.24–12.49; p < 0.0001; and Cobas®: 1T: 11.46–19.05; 2T: 9.65–14.67; 3T: 8.88–14.54; p < 0.0067). The FT4 RI during 1T determined LC/MS/MS was 8.75–18.27. D...
Objectives To describe the use and findings of cardiopulmonary imaging - chest X-ray (cX-ray), ec... more Objectives To describe the use and findings of cardiopulmonary imaging - chest X-ray (cX-ray), echocardiography (cEcho), chest CT (cCT), lung ultrasound (LUS)) and/or cardiac magnetic resonance imaging (cMRI) - in COVID-19-associated hospitalizations in Latin America (LATAM) Background The SARS-Cov-2 is one of the largest and most active threats to healthcare in living memory. There is an information gap on imaging services resources (ISR) used and their findings during the pandemic in LATAM. Methods This was a multicenter, prospective, observational study of COVID-19 inpatients conducted from March to December 2020 from 12 high-complexity centers in nine LATAM countries. Adults (> 18 yrs) with at least one imaging modality performed, followed from admission until discharge and/or in-hospital death, were included. Results We studied 1435 hospitalized patients (64% males) with a median age of 58 years classified into three regions: 262 from Mexico (Mx), 428 from Central America an...
Memórias do Instituto Oswaldo Cruz, 2020
BACKGROUND It was previously demonstrated that CMC-20, a nitazoxanide and N-methyl-1H-benzimidazo... more BACKGROUND It was previously demonstrated that CMC-20, a nitazoxanide and N-methyl-1H-benzimidazole hybrid molecule, had higher in vitro activity against Giardia intestinalis WB strain than metronidazole and albendazole and similar to nitazoxanide. OBJETIVES To evaluate the in vitro activity of CMC-20 against G. intestinalis strains with different susceptibility/resistance to albendazole and nitazoxanide and evaluate its effect on the distribution of parasite cytoskeletal proteins and its in vivo giardicidal activity. METHODS CMC-20 activity was tested against two isolates from patients with chronic and acute giardiasis, an experimentally induced albendazole resistant strain and a nitazoxanide resistant clinical isolate. CMC-20 effect on the distribution of parasite cytoskeletal proteins was analysed by indirect immunofluorescence and its activity was evaluated in a murine model of giardiasis. FINDINGS CMC-20 showed broad activity against susceptible and resistant strains to albendazole and nitaxozanide. It affected the parasite microtubule reservoir and triggered the parasite encystation. In this process, alpha-7.2 giardin co-localised with CWP-1 protein. CMC-20 reduced the infection time and cyst load in feces of G. muris infected mice similar to albendazole. MAIN CONCLUSIONS The in vitro and in vivo giardicidal activity of CMC-20 suggests its potential use in the treatment of giardiasis.
BMJ Open, 2019
IntroductionThis study aims to obtain data on the prevalence and incidence of structural heart di... more IntroductionThis study aims to obtain data on the prevalence and incidence of structural heart disease in a population setting and, to analyse and present those data on the application of spatial and machine learning methods that, although known to geography and statistics, need to become used for healthcare research and for political commitment to obtain resources and support effective public health programme implementation.Methods and analysisWe will perform a cross-sectional survey of randomly selected residents of Salamanca (Spain). 2400 individuals stratified by age and sex and by place of residence (rural and urban) will be studied. The variables to analyse will be obtained from the clinical history, different surveys including social status, Mediterranean diet, functional capacity, ECG, echocardiogram, VASERA and biochemical as well as genetic analysis.Ethics and disseminationThe study has been approved by the ethical committee of the healthcare community. All study participa...
Parasites & Vectors, 2018
Background: Babesia bovis belongs to the phylum Apicomplexa and is the major causal agent of bovi... more Background: Babesia bovis belongs to the phylum Apicomplexa and is the major causal agent of bovine babesiosis, the most important veterinary disease transmitted by arthropods. In apicomplexan parasites, the interaction between AMA1 and RON2 is necessary for the invasion process, and it is a target for vaccine development. In B. bovis, the existence of AMA1 has already been reported; however, the presence of a homolog of RON2 is unknown. The aim of this study was to characterize RON2 in B. bovis. Results: The B. bovis ron2 gene has a similar synteny with the orthologous gene in the B. bigemina genome. The entire ron2 gene was sequenced from different B. bovis strains showing > 99% similarity at the amino acid and nucleotide level among all the sequences obtained, including the characteristic CLAG domain for cytoadherence in the amino acid sequence, as is described in other Apicomplexa. The in silico transcription analysis showed similar levels of transcription between attenuated and virulent B. bovis strains, and expression of RON2 was confirmed by western blot in the B. bovis T3Bo virulent strain. Four conserved peptides, containing predicted B-cell epitopes in hydrophilic regions of the protein, were designed and chemically synthesized. The humoral immune response generated by the synthetic peptides was characterized in bovines, showing that anti-RON2 antibodies against peptides recognized intraerythrocytic merozoites of B. bovis. Only peptides P2 and P3 generated partially neutralizing antibodies that had an inhibitory effect of 28.10% and 21.42%, respectively, on the invasion process of B. bovis in bovine erythrocytes. Consistently, this effect is additive since inhibition increased to 42.09% when the antibodies were evaluated together. Finally, P2 and P3 peptides were also recognized by 83.33% and 87.77%, respectively, of naturally infected cattle from endemic areas. Conclusions: The data support RON2 as a novel B. bovis vaccine candidate antigen that contains conserved B-cell epitopes that elicit partially neutralizing antibodies.
The American journal of pathology, Aug 11, 2016
IL-8 promotes cancer cell growth, survival, angiogenesis, and metastasis in several tumors. Herei... more IL-8 promotes cancer cell growth, survival, angiogenesis, and metastasis in several tumors. Herein, we investigated the sources of IL-8 production in multiple myeloma (MM) and its potential roles in MM pathogenesis. We found that bone marrow cells from patients with MM secreted higher amounts of IL-8 than healthy donors. IL-8 production was detected in cultures of CD138(+) plasma cells and CD138(-) cells isolated from bone marrows of MM patients, and in three of seven human myeloma cell lines (HMCLs) analyzed. Interactions between MM and stromal cells increased IL-8 secretion by stromal cells through cell-cell adhesion and soluble factors. Interestingly, IL8 expression also increased in HMCLs, stromal cells, and osteoclasts after treatment with the antimyeloma drugs melphalan and bortezomib. In fact, the effect of bortezomib on IL-8 production was higher than that exerted by stromal-MM cell interactions. Addition of exogenous IL-8 did not affect growth of HMCLs, although it protecte...
General physiology and biophysics, 2002
Functional properties of myofibrils from chronically ischemic canine myocardium were evaluated. I... more Functional properties of myofibrils from chronically ischemic canine myocardium were evaluated. Ischemia was produced by tight stenosis of left anterior descending artery (LAD), followed by 40 min acute ischemia with prior preconditioning. Animals of the first group were sacrificed after 8 weeks. In the second group, angioplasty of LAD was performed after 8 weeks of ischemia and animals were kept alive for other 4 weeks. Control animals were sham operated. Activity and kinetic parameters of myofibrillar Ca2+-stimulated Mg2+-ATPase were measured in myofibrils isolated from anterior and posterior parts of all hearts. We did not find any differences in maximal velocity (Vmax), half-maximal activation constant for calcium (K(Ca2+)50) and cooperativity coefficient (n(hill)) of myofibrils from different experimental groups as compared to controls, either at pH 7, pH 6.5 (acidosis) or pH 7.5 (alkalosis). K(Ca2+)50 increased in medium simulated acidosis (12.6-33.5 times) and n(hill) decreas...
Developmental Dynamics, 2014
Background: Among the complexities of skeletal muscle differentiation is a temporal distinction i... more Background: Among the complexities of skeletal muscle differentiation is a temporal distinction in the onset of expression of different lineage‐specific genes. The lineage‐determining factor MyoD is bound to myogenic genes at the onset of differentiation whether gene activation is immediate or delayed. How temporal regulation of differentiation‐specific genes is established remains unclear. Results: Using embryonic tissue, we addressed the molecular differences in the organization of the myogenin and muscle creatine kinase (MCK) gene promoters by examining regulatory factor binding as a function of both time and spatial organization during somitogenesis. At the myogenin promoter, binding of the homeodomain factor Pbx1 coincided with H3 hyperacetylation and was followed by binding of co‐activators that modulate chromatin structure. MyoD and myogenin binding occurred subsequently, demonstrating that Pbx1 facilitates chromatin remodeling and modification before myogenic regulatory fact...
![Research paper thumbnail of [Spanish Registry on Cardiac Catheterization Interventions. 11th official report of the Working Group on Cardiac Catheterization and Interventional Cardiology of the Spanish Society of Cardiology (years 1990-2001)]](https://attachments.academia-assets.com/116995032/thumbnails/1.jpg)
](Revista española de cardiología, 2002
The results of the Spanish Registry of the Working Group on cardiac catheterization and Intervent... more The results of the Spanish Registry of the Working Group on cardiac catheterization and Interventional Cardiology of the Spanish Society of Cardiology (years 1990-2001) are presented. One-hundred-and-three centers contributed data, all the cardiac catheterization laboratories in Spain; 97 centers performed mainly adult catheterization and 6 carried out only pediatric procedures. In 2001, 95,430 diagnostic catheterization procedures were performed, with 79,607 coronary angiograms, representing a total increase of 8.4% over 2000. The population-adjusted incidence was 1947 coronary angiograms per 106 inhabitants. Coronary interventions increased by 15.4% compared with 2000, with a total of 31,290 procedures and an incidence of coronary interventions of 761 per 106 inhabitants. Coronary stents were the most frequently used devices with 39,356 implanted in 2001, and increase of 33.4% over 2000. Stenting accounted for 88.2% of procedures. Direct stenting was done in 11,280 procedures (40....
Clinical cancer research : an official journal of the American Association for Cancer Research, 2003
We investigated the ability of the fusion protein granulocyte-macrophage colony-stimulating facto... more We investigated the ability of the fusion protein granulocyte-macrophage colony-stimulating factor and carbonic anhydrase IX (GMCA-9)(1) to induce an immune response in vitro and in vivo for the development of a GMCA-9-based kidney cancer vaccine. Human dendritic cells (DCs) were transduced with a recombinant adenovirus containing the GMCA-9 gene and tested for their capacity to induce CA9-specific cytotoxic T lymphocytes in vitro. Tumor growth was studied in severe compromised immunodeficiency disease (SCID) mice s.c. injected with R11-GMCA-9, a human renal cell carcinoma cell line stably transfected with the GMCA-9 gene. Involvement of natural killer (NK) cells in the antitumor activity of GMCA-9 was determined in SCID mice treated with the NK-blocking agent anti-asialoGM-1. DC and R11 cells transduced with GMCA-9 produced a GMCA-9 protein that is targeted to the cell membrane and partially processed to granulocyte macrophage colony-stimulating factor- and CA9-like products. Furth...
Nature Communications, 2014
Magneto-fluorescent particles have been recognized as an emerging class of materials that exhibit... more Magneto-fluorescent particles have been recognized as an emerging class of materials that exhibit great potential in advanced applications. However, synthesizing such magnetofluorescent nanomaterials that simultaneously exhibit uniform and tunable sizes, high magnetic content loading, maximized fluorophore coverage at the surface and a versatile surface functionality has proven challenging. Here we report a simple approach for co-assembling magnetic nanoparticles with fluorescent quantum dots to form colloidal magneto-fluorescent supernanoparticles. Importantly, these supernanoparticles exhibit a superstructure consisting of a close-packed magnetic nanoparticle 'core', which is fully surrounded by a 'shell' of fluorescent quantum dots. A thin layer of silica coating provides high colloidal stability and biocompatibility, and a versatile surface functionality. We demonstrate that after surface pegylation, these silica-coated magneto-fluorescent supernanoparticles can be magnetically manipulated inside living cells while being optically tracked. Moreover, our silica-coated magneto-fluorescent supernanoparticles can also serve as an in vivo multi-photon and magnetic resonance dual-modal imaging probe.
Archivos de bronconeumologia, Jan 11, 2014
The effect of hereditary alpha-1 antitrypsin (AAT) deficiency can manifest clinically in the form... more The effect of hereditary alpha-1 antitrypsin (AAT) deficiency can manifest clinically in the form of chronic obstructive pulmonary disease (COPD). AAT deficiency (AATD) is defined as a serum concentration lower than 35% of the expected mean value or 50mg/dl (determined by nephelometry). It is associated in over 95% of cases with Pi*ZZ genotypes, and much less frequently with other genotypes resulting from combinations of Z, S, rare and null alleles. A systematic qualitative review was made of 107 articles, focusing mainly on an active search for AATD in COPD patients and intravenous (iv) treatment with AAT. On the basis of this review, the consultant committee of the Spanish Registry of Patients with AATD recommends that all COPD patients be screened for AATD with the determination of AAT serum concentrations, and when these are low, the evaluation must be completed with phenotyping and, on occasions, genotyping. Patients with severe AATD COPD should receive the pharmacological and ...
Case Reports in Urology, 2012
The incidence of malignant tumors in recipients of renal allografts is higher than in the general... more The incidence of malignant tumors in recipients of renal allografts is higher than in the general population. Renal cell carcinoma (RCC) accounts for 4.6% of the tumors in transplanted patients; of them, only 10% are found in transplanted kidneys. Transplantectomy has always been the usual treatment. However, during the last years, nephron-sparing surgery of the allograft is more frequently done in well-selected cases, and therefore dialysis can be avoided. We report the case of a 37-year-old female patient with renal transplant, diagnosed with a 4.5 cm tumor in the lower pole of the renal allograft. The patient underwent partial nephrectomy successfully. Six years after surgery, there is no evidence of recurrence of the disease and the patient maintains an adequate renal function.
Journal of High Energy Physics, 2012
A search for the standard model Higgs boson in the H → ZZ → 2ℓ2ν decay channel, where ℓ = e or μ,... more A search for the standard model Higgs boson in the H → ZZ → 2ℓ2ν decay channel, where ℓ = e or μ, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 fb−1. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.
Journal of High Energy Physics, 2012
A search for the standard model Higgs boson decaying into two Z bosons with subsequent decay into... more A search for the standard model Higgs boson decaying into two Z bosons with subsequent decay into a final state containing two quark jets and two leptons, H → ZZ(*) → q $ \overline {\text{q}} $ ℓ − ℓ + is presented. Results are based on data corresponding to an integrated luminosity of 4.6 fb−1 of proton-proton collisions at $ \sqrt {s} = 7 $ TeV, collected with the CMS detector at the LHC. In order to discriminate between signal and background events, kinematic and topological quantities, including the angular spin correlations of the decay products, are employed. Events are further classified according to the probability of the jets to originate from quarks of light or heavy flavor or from gluons. No evidence for the Higgs boson is found, and upper limits on its production cross section are determined for a Higgs boson of mass between 130 and 600 GeV.
REPRODUCTION, 2009
Glycolytic enzymes have, in addition to their role in energy production, other functions in the r... more Glycolytic enzymes have, in addition to their role in energy production, other functions in the regulation of cellular processes. Aldolase A has been reported to be present in sperm, playing a key role in glycolysis; however, despite its reported interactions with actin and WAS, little is known about a non-glycolytic role of aldolase A in sperm. Here, we show that in guinea pig spermatozoa, aldolase A is tightly associated to cytoskeletal structures where it interacts with actin, WAS, and Arp2/3. We show that aldolase A spermatozoa treatment increases their polymerized actin levels. In addition, we show that there is a direct correlation between the levels of polymerized actin and the levels of aldolase A–actin interaction. Our results suggest that aldolase A functions as a bridge between filaments of actin and the actin-polymerizing machinery.
Proceedings of the National Academy of Sciences, 2008
The molybdenum nitrogenase, present in a diverse group of bacteria and archea, is the major contr... more The molybdenum nitrogenase, present in a diverse group of bacteria and archea, is the major contributor to biological nitrogen fixation. The nitrogenase active site contains an iron–molybdenum cofactor (FeMo-co) composed of 7Fe, 9S, 1Mo, one unidentified light atom, and homocitrate. The nifQ gene was known to be involved in the incorporation of molybdenum into nitrogenase. Here we show direct biochemical evidence for the role of NifQ in FeMo-co biosynthesis. As-isolated NifQ was found to carry a molybdenum–iron–sulfur cluster that serves as a specific molybdenum donor for FeMo-co biosynthesis. Purified NifQ supported in vitro FeMo-co synthesis in the absence of an additional molybdenum source. The mobilization of molybdenum from NifQ required the simultaneous participation of NifH and NifEN in the in vitro FeMo-co synthesis assay, suggesting that NifQ would be the physiological molybdenum donor to a hypothetical NifEN/NifH complex.
Memórias do Instituto Oswaldo Cruz, 2013
Giardia lamblia is the causative agent of giardiasis in humans and several animal species, coloni... more Giardia lamblia is the causative agent of giardiasis in humans and several animal species, colonising the small intestinal lumen (Adam 2001). This parasite is widely distributed worldwide (Lengerich et al. 1994). The signs and symptoms of giardiasis include diarrhoea, abdominal pain, flatulence, weight loss and malabsorption of nutrients. In most cases, the infection remains asymptomatic (Adam 2001, Eckmann & Gillin 2001). The immunological mechanisms involved in clearance of Giardia infections are not fully elucidated. In immunocompetent patients, the infection is self-limiting, which indicates the presence of effective host defence mechanisms against this intestinal parasite (Faubert 2000, Eckmann 2003). The humoral and cellular immune responses play an important role in the control of Giardia infections (Faubert 2000, Singer & Nash 2000, Roxstrom-Lindquist et al. 2006). However, our knowledge about the immunogenic antigens of G. lamblia is limited. Several antigenic proteins of G. lamblia have been described, including variable surface proteins (VSPs), cyst wall proteins (CWPs), giardins, tubulins, arginine deaminase, ornithine carbamoyl transferase and enolase, among others (Luján et al. 1995, Langford et al. 2002, Abdul-Wahid & Faubert 2004, Davids et al. 2006). Several of these molecules are recognised by the systemic and secretory antibody responses of infected humans and mice (Palm et al. 2003, Abdul-Wahid & Faubert 2004, Téllez et al. 2005, Davids et al. 2006). The proteins α-1 giardin and CWP-2 provide marked protection against G. lamblia infection (Larocque et al. 2003, Jenikova et al. 2011). The purpose of this study was to identify and characterise the immunogenic proteins of G. lamblia in a mouse model by generating monoclonal antibodies (moAbs) specific to G. lamblia by using splenocytes derived from infected mice. Those moAbs will help to further characterise the Giardia antigens that are recognised during infection. MATERIALS AND METHODS Mice-C3H/HeJ mice were purchased from The Jackson Laboratory (Bar Harbor, ME, USA). This strain of mouse is susceptible to infection with the G. lamblia clone GS/M-83-H7 (Byrd et al. 1994). G. lamblia culture-G. lamblia trophozoites [clone GS/M-83-H7 (ATCC 50581)] were obtained from the American Type Culture Collection. Axenic G. lamblia cultures were maintained in the TYI-S-33 medium, which was supplemented with newborn calf serum (NBCS) and antibiotics at 37ºC. G. lamblia protein extract-G. lamblia soluble extract proteins were obtained using the method described by Gottstein et al. (1990), with slight modifications.
Medical Mycology, 2012
The severity of histoplasmosis varies greatly depending on the intensity of exposure to the fungu... more The severity of histoplasmosis varies greatly depending on the intensity of exposure to the fungus and on the immune status of the infected individual [1,5]. In patients with immunodefi ciency disorders, especially those infected with the human immunodefi ciency virus (HIV), histoplasmosis is considered an opportunistic infection [6-8]. In addition, in a high proportion of the cases this fungal infection manifests as a severe disseminated process that often leads to death if not treated promptly [6-8]. Diagnosis of histoplasmosis is usually accomplished by recovery of the etiologic agent in culture and microscopic examination of respiratory tract specimens, biopsies, and body fl uid specimens. However, these techniques yield positive results in only approximately 50% of proven cases [1,3,9]. In addition, isolation of the fungus usually takes 2-6 weeks, delaying diagnosis and initiation of therapy. Immunological tests that detect antibodies and/or antigens
Physical Review Letters, 2012
Journal of Clinical Medicine, 2021
Background: Recent guidelines recommend establishing a local reference interval (RI) for thyroid ... more Background: Recent guidelines recommend establishing a local reference interval (RI) for thyroid function. We aimed to establish trimester-specific RIs for thyrotropin (TSH) and free thyroxine (FT4) in a cohort of healthy pregnant women in Catalonia (Spain). Methods: A prospective observational study was conducted with 332 healthy pregnant women, from the first trimester (1T) to delivery. TSH was measured using an Architect® immunoassay (Abbott) and FT4 by two immunoassays, Architect® (Abbott) and Cobas® (Roche), in the three trimesters. FT4 was also measured by liquid chromatography mass spectrometry (LC/MS/MS) in the 1T. Results: TSH (µUI/mL) increased throughout pregnancy (1T: 0.03–3.78; 2T: 0.51–3.53; 3T: 0.50–4.32; p < 0.0001) and FT4 (pmol/L) progressively decreased (Architect® 1T: 10.42–15.96; 2T: 8.37–12.74; 3T: 8.24–12.49; p < 0.0001; and Cobas®: 1T: 11.46–19.05; 2T: 9.65–14.67; 3T: 8.88–14.54; p < 0.0067). The FT4 RI during 1T determined LC/MS/MS was 8.75–18.27. D...
Objectives To describe the use and findings of cardiopulmonary imaging - chest X-ray (cX-ray), ec... more Objectives To describe the use and findings of cardiopulmonary imaging - chest X-ray (cX-ray), echocardiography (cEcho), chest CT (cCT), lung ultrasound (LUS)) and/or cardiac magnetic resonance imaging (cMRI) - in COVID-19-associated hospitalizations in Latin America (LATAM) Background The SARS-Cov-2 is one of the largest and most active threats to healthcare in living memory. There is an information gap on imaging services resources (ISR) used and their findings during the pandemic in LATAM. Methods This was a multicenter, prospective, observational study of COVID-19 inpatients conducted from March to December 2020 from 12 high-complexity centers in nine LATAM countries. Adults (> 18 yrs) with at least one imaging modality performed, followed from admission until discharge and/or in-hospital death, were included. Results We studied 1435 hospitalized patients (64% males) with a median age of 58 years classified into three regions: 262 from Mexico (Mx), 428 from Central America an...
Memórias do Instituto Oswaldo Cruz, 2020
BACKGROUND It was previously demonstrated that CMC-20, a nitazoxanide and N-methyl-1H-benzimidazo... more BACKGROUND It was previously demonstrated that CMC-20, a nitazoxanide and N-methyl-1H-benzimidazole hybrid molecule, had higher in vitro activity against Giardia intestinalis WB strain than metronidazole and albendazole and similar to nitazoxanide. OBJETIVES To evaluate the in vitro activity of CMC-20 against G. intestinalis strains with different susceptibility/resistance to albendazole and nitazoxanide and evaluate its effect on the distribution of parasite cytoskeletal proteins and its in vivo giardicidal activity. METHODS CMC-20 activity was tested against two isolates from patients with chronic and acute giardiasis, an experimentally induced albendazole resistant strain and a nitazoxanide resistant clinical isolate. CMC-20 effect on the distribution of parasite cytoskeletal proteins was analysed by indirect immunofluorescence and its activity was evaluated in a murine model of giardiasis. FINDINGS CMC-20 showed broad activity against susceptible and resistant strains to albendazole and nitaxozanide. It affected the parasite microtubule reservoir and triggered the parasite encystation. In this process, alpha-7.2 giardin co-localised with CWP-1 protein. CMC-20 reduced the infection time and cyst load in feces of G. muris infected mice similar to albendazole. MAIN CONCLUSIONS The in vitro and in vivo giardicidal activity of CMC-20 suggests its potential use in the treatment of giardiasis.
BMJ Open, 2019
IntroductionThis study aims to obtain data on the prevalence and incidence of structural heart di... more IntroductionThis study aims to obtain data on the prevalence and incidence of structural heart disease in a population setting and, to analyse and present those data on the application of spatial and machine learning methods that, although known to geography and statistics, need to become used for healthcare research and for political commitment to obtain resources and support effective public health programme implementation.Methods and analysisWe will perform a cross-sectional survey of randomly selected residents of Salamanca (Spain). 2400 individuals stratified by age and sex and by place of residence (rural and urban) will be studied. The variables to analyse will be obtained from the clinical history, different surveys including social status, Mediterranean diet, functional capacity, ECG, echocardiogram, VASERA and biochemical as well as genetic analysis.Ethics and disseminationThe study has been approved by the ethical committee of the healthcare community. All study participa...
Parasites & Vectors, 2018
Background: Babesia bovis belongs to the phylum Apicomplexa and is the major causal agent of bovi... more Background: Babesia bovis belongs to the phylum Apicomplexa and is the major causal agent of bovine babesiosis, the most important veterinary disease transmitted by arthropods. In apicomplexan parasites, the interaction between AMA1 and RON2 is necessary for the invasion process, and it is a target for vaccine development. In B. bovis, the existence of AMA1 has already been reported; however, the presence of a homolog of RON2 is unknown. The aim of this study was to characterize RON2 in B. bovis. Results: The B. bovis ron2 gene has a similar synteny with the orthologous gene in the B. bigemina genome. The entire ron2 gene was sequenced from different B. bovis strains showing > 99% similarity at the amino acid and nucleotide level among all the sequences obtained, including the characteristic CLAG domain for cytoadherence in the amino acid sequence, as is described in other Apicomplexa. The in silico transcription analysis showed similar levels of transcription between attenuated and virulent B. bovis strains, and expression of RON2 was confirmed by western blot in the B. bovis T3Bo virulent strain. Four conserved peptides, containing predicted B-cell epitopes in hydrophilic regions of the protein, were designed and chemically synthesized. The humoral immune response generated by the synthetic peptides was characterized in bovines, showing that anti-RON2 antibodies against peptides recognized intraerythrocytic merozoites of B. bovis. Only peptides P2 and P3 generated partially neutralizing antibodies that had an inhibitory effect of 28.10% and 21.42%, respectively, on the invasion process of B. bovis in bovine erythrocytes. Consistently, this effect is additive since inhibition increased to 42.09% when the antibodies were evaluated together. Finally, P2 and P3 peptides were also recognized by 83.33% and 87.77%, respectively, of naturally infected cattle from endemic areas. Conclusions: The data support RON2 as a novel B. bovis vaccine candidate antigen that contains conserved B-cell epitopes that elicit partially neutralizing antibodies.
The American journal of pathology, Aug 11, 2016
IL-8 promotes cancer cell growth, survival, angiogenesis, and metastasis in several tumors. Herei... more IL-8 promotes cancer cell growth, survival, angiogenesis, and metastasis in several tumors. Herein, we investigated the sources of IL-8 production in multiple myeloma (MM) and its potential roles in MM pathogenesis. We found that bone marrow cells from patients with MM secreted higher amounts of IL-8 than healthy donors. IL-8 production was detected in cultures of CD138(+) plasma cells and CD138(-) cells isolated from bone marrows of MM patients, and in three of seven human myeloma cell lines (HMCLs) analyzed. Interactions between MM and stromal cells increased IL-8 secretion by stromal cells through cell-cell adhesion and soluble factors. Interestingly, IL8 expression also increased in HMCLs, stromal cells, and osteoclasts after treatment with the antimyeloma drugs melphalan and bortezomib. In fact, the effect of bortezomib on IL-8 production was higher than that exerted by stromal-MM cell interactions. Addition of exogenous IL-8 did not affect growth of HMCLs, although it protecte...
General physiology and biophysics, 2002
Functional properties of myofibrils from chronically ischemic canine myocardium were evaluated. I... more Functional properties of myofibrils from chronically ischemic canine myocardium were evaluated. Ischemia was produced by tight stenosis of left anterior descending artery (LAD), followed by 40 min acute ischemia with prior preconditioning. Animals of the first group were sacrificed after 8 weeks. In the second group, angioplasty of LAD was performed after 8 weeks of ischemia and animals were kept alive for other 4 weeks. Control animals were sham operated. Activity and kinetic parameters of myofibrillar Ca2+-stimulated Mg2+-ATPase were measured in myofibrils isolated from anterior and posterior parts of all hearts. We did not find any differences in maximal velocity (Vmax), half-maximal activation constant for calcium (K(Ca2+)50) and cooperativity coefficient (n(hill)) of myofibrils from different experimental groups as compared to controls, either at pH 7, pH 6.5 (acidosis) or pH 7.5 (alkalosis). K(Ca2+)50 increased in medium simulated acidosis (12.6-33.5 times) and n(hill) decreas...
Developmental Dynamics, 2014
Background: Among the complexities of skeletal muscle differentiation is a temporal distinction i... more Background: Among the complexities of skeletal muscle differentiation is a temporal distinction in the onset of expression of different lineage‐specific genes. The lineage‐determining factor MyoD is bound to myogenic genes at the onset of differentiation whether gene activation is immediate or delayed. How temporal regulation of differentiation‐specific genes is established remains unclear. Results: Using embryonic tissue, we addressed the molecular differences in the organization of the myogenin and muscle creatine kinase (MCK) gene promoters by examining regulatory factor binding as a function of both time and spatial organization during somitogenesis. At the myogenin promoter, binding of the homeodomain factor Pbx1 coincided with H3 hyperacetylation and was followed by binding of co‐activators that modulate chromatin structure. MyoD and myogenin binding occurred subsequently, demonstrating that Pbx1 facilitates chromatin remodeling and modification before myogenic regulatory fact...
Revista española de cardiología, 2002
The results of the Spanish Registry of the Working Group on cardiac catheterization and Intervent... more The results of the Spanish Registry of the Working Group on cardiac catheterization and Interventional Cardiology of the Spanish Society of Cardiology (years 1990-2001) are presented. One-hundred-and-three centers contributed data, all the cardiac catheterization laboratories in Spain; 97 centers performed mainly adult catheterization and 6 carried out only pediatric procedures. In 2001, 95,430 diagnostic catheterization procedures were performed, with 79,607 coronary angiograms, representing a total increase of 8.4% over 2000. The population-adjusted incidence was 1947 coronary angiograms per 106 inhabitants. Coronary interventions increased by 15.4% compared with 2000, with a total of 31,290 procedures and an incidence of coronary interventions of 761 per 106 inhabitants. Coronary stents were the most frequently used devices with 39,356 implanted in 2001, and increase of 33.4% over 2000. Stenting accounted for 88.2% of procedures. Direct stenting was done in 11,280 procedures (40....
Clinical cancer research : an official journal of the American Association for Cancer Research, 2003
We investigated the ability of the fusion protein granulocyte-macrophage colony-stimulating facto... more We investigated the ability of the fusion protein granulocyte-macrophage colony-stimulating factor and carbonic anhydrase IX (GMCA-9)(1) to induce an immune response in vitro and in vivo for the development of a GMCA-9-based kidney cancer vaccine. Human dendritic cells (DCs) were transduced with a recombinant adenovirus containing the GMCA-9 gene and tested for their capacity to induce CA9-specific cytotoxic T lymphocytes in vitro. Tumor growth was studied in severe compromised immunodeficiency disease (SCID) mice s.c. injected with R11-GMCA-9, a human renal cell carcinoma cell line stably transfected with the GMCA-9 gene. Involvement of natural killer (NK) cells in the antitumor activity of GMCA-9 was determined in SCID mice treated with the NK-blocking agent anti-asialoGM-1. DC and R11 cells transduced with GMCA-9 produced a GMCA-9 protein that is targeted to the cell membrane and partially processed to granulocyte macrophage colony-stimulating factor- and CA9-like products. Furth...
Nature Communications, 2014
Magneto-fluorescent particles have been recognized as an emerging class of materials that exhibit... more Magneto-fluorescent particles have been recognized as an emerging class of materials that exhibit great potential in advanced applications. However, synthesizing such magnetofluorescent nanomaterials that simultaneously exhibit uniform and tunable sizes, high magnetic content loading, maximized fluorophore coverage at the surface and a versatile surface functionality has proven challenging. Here we report a simple approach for co-assembling magnetic nanoparticles with fluorescent quantum dots to form colloidal magneto-fluorescent supernanoparticles. Importantly, these supernanoparticles exhibit a superstructure consisting of a close-packed magnetic nanoparticle 'core', which is fully surrounded by a 'shell' of fluorescent quantum dots. A thin layer of silica coating provides high colloidal stability and biocompatibility, and a versatile surface functionality. We demonstrate that after surface pegylation, these silica-coated magneto-fluorescent supernanoparticles can be magnetically manipulated inside living cells while being optically tracked. Moreover, our silica-coated magneto-fluorescent supernanoparticles can also serve as an in vivo multi-photon and magnetic resonance dual-modal imaging probe.
Archivos de bronconeumologia, Jan 11, 2014
The effect of hereditary alpha-1 antitrypsin (AAT) deficiency can manifest clinically in the form... more The effect of hereditary alpha-1 antitrypsin (AAT) deficiency can manifest clinically in the form of chronic obstructive pulmonary disease (COPD). AAT deficiency (AATD) is defined as a serum concentration lower than 35% of the expected mean value or 50mg/dl (determined by nephelometry). It is associated in over 95% of cases with Pi*ZZ genotypes, and much less frequently with other genotypes resulting from combinations of Z, S, rare and null alleles. A systematic qualitative review was made of 107 articles, focusing mainly on an active search for AATD in COPD patients and intravenous (iv) treatment with AAT. On the basis of this review, the consultant committee of the Spanish Registry of Patients with AATD recommends that all COPD patients be screened for AATD with the determination of AAT serum concentrations, and when these are low, the evaluation must be completed with phenotyping and, on occasions, genotyping. Patients with severe AATD COPD should receive the pharmacological and ...
Case Reports in Urology, 2012
The incidence of malignant tumors in recipients of renal allografts is higher than in the general... more The incidence of malignant tumors in recipients of renal allografts is higher than in the general population. Renal cell carcinoma (RCC) accounts for 4.6% of the tumors in transplanted patients; of them, only 10% are found in transplanted kidneys. Transplantectomy has always been the usual treatment. However, during the last years, nephron-sparing surgery of the allograft is more frequently done in well-selected cases, and therefore dialysis can be avoided. We report the case of a 37-year-old female patient with renal transplant, diagnosed with a 4.5 cm tumor in the lower pole of the renal allograft. The patient underwent partial nephrectomy successfully. Six years after surgery, there is no evidence of recurrence of the disease and the patient maintains an adequate renal function.
Journal of High Energy Physics, 2012
A search for the standard model Higgs boson in the H → ZZ → 2ℓ2ν decay channel, where ℓ = e or μ,... more A search for the standard model Higgs boson in the H → ZZ → 2ℓ2ν decay channel, where ℓ = e or μ, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 fb−1. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.
Journal of High Energy Physics, 2012
A search for the standard model Higgs boson decaying into two Z bosons with subsequent decay into... more A search for the standard model Higgs boson decaying into two Z bosons with subsequent decay into a final state containing two quark jets and two leptons, H → ZZ(*) → q $ \overline {\text{q}} $ ℓ − ℓ + is presented. Results are based on data corresponding to an integrated luminosity of 4.6 fb−1 of proton-proton collisions at $ \sqrt {s} = 7 $ TeV, collected with the CMS detector at the LHC. In order to discriminate between signal and background events, kinematic and topological quantities, including the angular spin correlations of the decay products, are employed. Events are further classified according to the probability of the jets to originate from quarks of light or heavy flavor or from gluons. No evidence for the Higgs boson is found, and upper limits on its production cross section are determined for a Higgs boson of mass between 130 and 600 GeV.
REPRODUCTION, 2009
Glycolytic enzymes have, in addition to their role in energy production, other functions in the r... more Glycolytic enzymes have, in addition to their role in energy production, other functions in the regulation of cellular processes. Aldolase A has been reported to be present in sperm, playing a key role in glycolysis; however, despite its reported interactions with actin and WAS, little is known about a non-glycolytic role of aldolase A in sperm. Here, we show that in guinea pig spermatozoa, aldolase A is tightly associated to cytoskeletal structures where it interacts with actin, WAS, and Arp2/3. We show that aldolase A spermatozoa treatment increases their polymerized actin levels. In addition, we show that there is a direct correlation between the levels of polymerized actin and the levels of aldolase A–actin interaction. Our results suggest that aldolase A functions as a bridge between filaments of actin and the actin-polymerizing machinery.
Proceedings of the National Academy of Sciences, 2008
The molybdenum nitrogenase, present in a diverse group of bacteria and archea, is the major contr... more The molybdenum nitrogenase, present in a diverse group of bacteria and archea, is the major contributor to biological nitrogen fixation. The nitrogenase active site contains an iron–molybdenum cofactor (FeMo-co) composed of 7Fe, 9S, 1Mo, one unidentified light atom, and homocitrate. The nifQ gene was known to be involved in the incorporation of molybdenum into nitrogenase. Here we show direct biochemical evidence for the role of NifQ in FeMo-co biosynthesis. As-isolated NifQ was found to carry a molybdenum–iron–sulfur cluster that serves as a specific molybdenum donor for FeMo-co biosynthesis. Purified NifQ supported in vitro FeMo-co synthesis in the absence of an additional molybdenum source. The mobilization of molybdenum from NifQ required the simultaneous participation of NifH and NifEN in the in vitro FeMo-co synthesis assay, suggesting that NifQ would be the physiological molybdenum donor to a hypothetical NifEN/NifH complex.
Memórias do Instituto Oswaldo Cruz, 2013
Giardia lamblia is the causative agent of giardiasis in humans and several animal species, coloni... more Giardia lamblia is the causative agent of giardiasis in humans and several animal species, colonising the small intestinal lumen (Adam 2001). This parasite is widely distributed worldwide (Lengerich et al. 1994). The signs and symptoms of giardiasis include diarrhoea, abdominal pain, flatulence, weight loss and malabsorption of nutrients. In most cases, the infection remains asymptomatic (Adam 2001, Eckmann & Gillin 2001). The immunological mechanisms involved in clearance of Giardia infections are not fully elucidated. In immunocompetent patients, the infection is self-limiting, which indicates the presence of effective host defence mechanisms against this intestinal parasite (Faubert 2000, Eckmann 2003). The humoral and cellular immune responses play an important role in the control of Giardia infections (Faubert 2000, Singer & Nash 2000, Roxstrom-Lindquist et al. 2006). However, our knowledge about the immunogenic antigens of G. lamblia is limited. Several antigenic proteins of G. lamblia have been described, including variable surface proteins (VSPs), cyst wall proteins (CWPs), giardins, tubulins, arginine deaminase, ornithine carbamoyl transferase and enolase, among others (Luján et al. 1995, Langford et al. 2002, Abdul-Wahid & Faubert 2004, Davids et al. 2006). Several of these molecules are recognised by the systemic and secretory antibody responses of infected humans and mice (Palm et al. 2003, Abdul-Wahid & Faubert 2004, Téllez et al. 2005, Davids et al. 2006). The proteins α-1 giardin and CWP-2 provide marked protection against G. lamblia infection (Larocque et al. 2003, Jenikova et al. 2011). The purpose of this study was to identify and characterise the immunogenic proteins of G. lamblia in a mouse model by generating monoclonal antibodies (moAbs) specific to G. lamblia by using splenocytes derived from infected mice. Those moAbs will help to further characterise the Giardia antigens that are recognised during infection. MATERIALS AND METHODS Mice-C3H/HeJ mice were purchased from The Jackson Laboratory (Bar Harbor, ME, USA). This strain of mouse is susceptible to infection with the G. lamblia clone GS/M-83-H7 (Byrd et al. 1994). G. lamblia culture-G. lamblia trophozoites [clone GS/M-83-H7 (ATCC 50581)] were obtained from the American Type Culture Collection. Axenic G. lamblia cultures were maintained in the TYI-S-33 medium, which was supplemented with newborn calf serum (NBCS) and antibiotics at 37ºC. G. lamblia protein extract-G. lamblia soluble extract proteins were obtained using the method described by Gottstein et al. (1990), with slight modifications.
Medical Mycology, 2012
The severity of histoplasmosis varies greatly depending on the intensity of exposure to the fungu... more The severity of histoplasmosis varies greatly depending on the intensity of exposure to the fungus and on the immune status of the infected individual [1,5]. In patients with immunodefi ciency disorders, especially those infected with the human immunodefi ciency virus (HIV), histoplasmosis is considered an opportunistic infection [6-8]. In addition, in a high proportion of the cases this fungal infection manifests as a severe disseminated process that often leads to death if not treated promptly [6-8]. Diagnosis of histoplasmosis is usually accomplished by recovery of the etiologic agent in culture and microscopic examination of respiratory tract specimens, biopsies, and body fl uid specimens. However, these techniques yield positive results in only approximately 50% of proven cases [1,3,9]. In addition, isolation of the fungus usually takes 2-6 weeks, delaying diagnosis and initiation of therapy. Immunological tests that detect antibodies and/or antigens