Anti-toxoplasma activity and DNA-binding of copper(II) and zinc(II) coordination compounds with 5-nitroimidazole-based ligands.

Tetrahedral copper(II) and zinc(II) coordination compounds from 5-nitroimidazole derivatives, viz. 1-(2-chloroethyl)-2-methyl-5-nitroimidazole (cenz) and ornidazole 1-(3-chloro-2-hydroxypropyl)-2-methyl-5-nitroimidazole (onz), were synthesized and spectroscopically characterized. Their molecular structures were determined by X-ray diffraction studies. The complexes [Cu(onz)2X2], [Zn(onz)2X2], [Cu(cenz)2X2] and [Zn(cenz)2X2] (X- = Cl, Br), are stable in solution and exhibit positive LogD7.4 values that are in the range for molecules capable of crossing the cell membrane via passive difussion. Their biological activity against Toxoplasma gondi was investigated, and IC50 and lethal dose (LD50) values were determined. The ornidazole copper(II) compounds showed very good antiparasitic activity in its tachyzoite morphology. The interaction of the coordination compounds with DNA was examined by circular dichroism, fluorescence (using intercalating ethidium bromide and minor groove binding Hoechst 33258) and UV-Vis spectroscopy. The copper(II) compounds interact with the minor groove of the biomolecule, whereas weaker electrostatic interactions take place with the zinc(II) compounds. The spectroscopic data achieved for the two series of complexes (namely with copper(II) and zinc(II) as metal center) agree with the respective DNA-damage features observed by gel electrophoresis.

Caveats of chimpanzee ChAdOx1 adenovirus-vectored vaccines to boost anti-SARS-CoV-2 protective immunity in mice.

Several COVID-19 vaccines use adenovirus vectors to deliver the SARS-CoV-2 spike (S) protein. Immunization with these vaccines promotes immunity against the S protein, but against also the adenovirus itself. This could interfere with the entry of the vaccine into the cell, reducing its efficacy. Herein, we evaluate the efficiency of an adenovirus-vectored vaccine (chimpanzee ChAdOx1 adenovirus, AZD1222) in boosting the specific immunity compared to that induced by a recombinant receptor-binding domain (RBD)-based vaccine without viral vector. Mice immunized with the AZD1222 human vaccine were given a booster 6 months later, with either the homologous vaccine or a recombinant vaccine based on RBD of the delta variant, which was prevalent at the start of this study. A significant increase in anti-RBD antibody levels was observed in rRBD-boosted mice (31-61%) compared to those receiving two doses of AZD1222 (0%). Significantly higher rates of PepMix™- or RBD-elicited proliferation were also observed in IFNγ-producing CD4 and CD8 cells from mice boosted with one or two doses of RBD, respectively. The lower efficiency of the ChAdOx1-S vaccine in boosting specific immunity could be the result of a pre-existing anti-vector immunity, induced by increased levels of anti-adenovirus antibodies found both in mice and humans. Taken together, these results point to the importance of avoiding the recurrent use of the same adenovirus vector in individuals with immunity and memory against them. It also illustrates the disadvantages of ChAdOx1 adenovirus-vectored vaccine with respect to recombinant protein vaccines, which can be used without restriction in vaccine-booster programs. KEY POINTS: • ChAdOx1 adenovirus vaccine (AZD1222) may not be effective in boosting anti-SARS-CoV-2 immunity • A recombinant RBD protein vaccine is effective in boosting anti-SARS-CoV-2 immunity in mice • Antibodies elicited by the rRBD-delta vaccine persisted for up to 3 months in mice.

Effects of Etomidate on Postintubation Hypotension, Inflammatory Markers, and Mortality in Critically Ill Patients with COVID-19: An International, Multicenter, Retrospective Study.

OBJECTIVE: To evaluate the association of etomidate with postintubation hypotension, inflammation, and mortality in critically ill patients with COVID-19. DESIGN: International, multicenter, retrospective study. PARTICIPANTS: Critically ill patients hospitalized specifically for COVID-19 from three major academic institutions in the US and Europe. MAIN OUTCOME AND MEASURES: Patients were allocated into the etomidate (ET) group or another induction agent (OA) group. The primary outcome was postintubation hypotension. Secondary outcomes included postintubation inflammatory status, in-hospital mortality, and mortality at 30 days. RESULTS: 171 patients with a median age of 68 (IQR 58-73) years were included (ET, n = 98; OA, n = 73). Etomidate was associated with lower postintubation mean arterial pressure [74.33 (64-85) mm Hg versus 81.84 (69.75-94.25) mm Hg, p = 0.005] compared to other agents. No statistically significant differences were generally observed in inflammatory markers between the two groups at 7- and 14-days after admission to the intensive care unit. In-hospital mortality [77 (79%) versus 41 (56%), p = 0.003] and mortality at 30-days [78 (80%) versus 43 (59%), p = 0.006] were higher in the ET group. In multivariate logistic regression analysis, only etomidate (p = 0.009) and postintubation mean arterial pressure (p < 0.001) had a statistically significant effect on mortality, in contrast to stress-dose steroids (p = 0.301), after adjusting for creatinine (p = 0.695), blood urea nitrogen (p = 0.153), age (p = 0.055), oxygen saturation of hemoglobin (SpO2) (p = 0.941), and fraction of inspired oxygen (FiO2) (p = 0.712). CONCLUSIONS: Administration of a single-bolus dose of etomidate in critically ill patients with COVID-19 is associated with lower postintubation mean arterial pressure and higher in-hospital and 30-day mortality compared to other induction agents.

AS1411 Nucleolin-Specific Binding Aptamers Reduce Pathological Angiogenesis through Inhibition of Nucleolin Phosphorylation.

Proliferative retinopathies produces an irreversible type of blindness affecting working age and pediatric population of industrialized countries. Despite the good results of anti-VEGF therapy, intraocular and systemic complications are often associated after its intravitreal use, hence novel therapeutic approaches are needed. The aim of the present study is to test the effect of the AS1411, an antiangiogenic nucleolin-binding aptamer, using in vivo, ex vivo and in vitro models of angiogenesis and propose a mechanistic insight. Our results showed that AS1411 significantly inhibited retinal neovascularization in the oxygen induced retinopathy (OIR) in vivo model, as well as inhibited branch formation in the rat aortic ex vivo assay, and, significantly reduced proliferation, cell migration and tube formation in the HUVEC in vitro model. Importantly, phosphorylated NCL protein was significantly abolished in HUVEC in the presence of AS1411 without affecting NFκB phosphorylation and -21 and 221-angiomiRs, suggesting that the antiangiogenic properties of this molecule are partially mediated by a down regulation in NCL phosphorylation. In sum, this new research further supports the NCL role in the molecular etiology of pathological angiogenesis and identifies AS1411 as a novel anti-angiogenic treatment.

Differential Susceptibility of Xylella fastidiosa Strains to Synthetic Bactericidal Peptides.

The kinetics of cell inactivation and the susceptibility of Xylella fastidiosa subspecies fastidiosa, multiplex, and pauca to synthetic antimicrobial peptides from two libraries (CECMEL11 and CYCLO10) were studied. The bactericidal effect was dependent on the relative concentrations of peptide and bacterial cells, and was influenced by the diluent, either buffer or sap. The most bactericidal and lytic peptide was BP178, an enlarged derivative of the amphipathic cationic linear undecapeptide BP100. The maximum reduction in survivors after BP178 treatment occurred within the first 10 to 20 min of contact and at micromolar concentrations (<10 µM), resulting in pore formation in cell membranes, abundant production of outer membrane vesicles, and lysis. A threshold ratio of 109 molecules of peptide per bacterial cell was estimated to be necessary to initiate cell inactivation. There was a differential susceptibility to BP178 among strains, with DD1 being the most resistant and CFBP 8173 the most susceptible. Moreover, strains showed a proportion of cells under the viable but nonculturable state, which was highly variable among strains. These findings may have implications for managing the diseases caused by X. fastidiosa.

Exposure to bisphenol A: current levels from food intake are toxic to human cells.

In the present work, cell lines of different origin were exposed to BPA levels from food intake reported elsewhere. Specifically, we used an in vitro assay to determine cytotoxicity of BPA in three cell lines: MCF7 (breast cancer), PC3 (prostate cancer) and 3T3-L1 (mouse fibroblast). Cytotoxic effects were observed at concentrations higher than 50 µg/mL which is above the involuntary exposure level of BPA described before in fresh, canned and frozen foods and beverages. Furthermore, medial inhibitory concentrations (IC50) of 85.17 µg/mL and 88.48 µg/mL were observed for PC3 and 3T3-L1, respectively, and a slightly lower IC50 of 64.67 µg/mL for MCF7. These results highlight BPA's toxicity potential at current levels from food intake. The cell line-dependent divergent response to BPA reported herein is discussed.

Preclinical evidences of safety of a new synthetic adjuvant to formulate with the influenza human vaccine: absence of subchronic toxicity and mutagenicity.

Context: Influenza is a severe, life-threatening viral disease that can be prevented by vaccination. However, the anti-influenza human vaccine failed to show the required efficacy both in infants under 5 years old and in the elder population, who are among those with the highest risk of developing severe complications after influenza infection. Therefore, it is of high importance to improve the vaccine efficacy and ensure its safety in these susceptible populations. GK-1, a novel 18-aa peptide adjuvant, has been proved to increase the immunogenicity of the human influenza vaccine in both young and aged mice. Objective: A preclinical study of the toxicity profile of GK-1 following the World Health Organization guidelines to support its use was herein conducted. Material and methods: GK-1 was synthetically produced following Good Manufacturing Practices. The toxicological evaluation of GK-1 peptide was performed in rats after repeated dose-ranging trials by the subcutaneous route. The mutagenic potential of GK-1 was assessed by the micronucleus, chromosomal aberration, and Ames tests, in accordance with OECD Guidelines. Results: GK-1 did not show toxic effects at doses up to 12.5mg/kg, corresponding to 25 times the dose intended for human use. No indications of mutagenic potential were observed. GK-1 after dermal administration was well tolerated locally. Conclusion: The efficacy of GK-1 to improve influenza vaccine protection, along with the absence of toxicity and mutagenicity, as reported herein, support the evaluation of this peptide in a clinical trial as a novel adjuvant for human use.

[Development of a tool to conduct family studies in primary health care]. / Estudio de familia en Atención Primaria: construcción y validación de una herramienta para la valoración familiar.

BACKGROUND: The Family and Community Health Model (MAIS) establishes the continuity of care as an essential principle. The Family Study, as a clinical strategy, allows to have sufficient and timely information and knowledge about users of health care services, facilitates their accompaniment and is a source of information to improve the quality of care and the management of health centers. AIM: To develop a tool to conduct family studies, devised by experts in Primary Health Care. MATERIAL AND METHODS: Using a qualitative method, an electronic Delphi was conducted on 24 experts on primary health care. Afterwards, the content validation was carried out with the participation of judges. RESULTS: The resulting tool considers two levels of family assessment. It allows to distinguish those families that would benefit from interventions of greater complexity than those derived from the usual care of health centers. CONCLUSIONS: The tool to perform family studies responds to the informational and continuity component of Continuity of Patient Care principle. It may be a proposal for the continuous improvement of Chilean primary care.

[User Participation in Clinical Decision-making in Primary Health Care in ChileParticipação dos usuários nas decisões clínicas na atenção primária à saúde no Chile]. / Participación de los usuarios en las decisiones clínicas en la atención primaria de salud en Chile.

OBJECTIVE: Describe users' experience with participation in clinical decision-making at Family Health Centers (CESFAM) in the Primary Health Care (PHC) system. METHODS: Qualitative descriptive study. Focus groups made up of CESFAM users were held in southeastern Santiago, Chile, and the information was thematically analyzed using Atlas.ti version 6® software. RESULTS: Five focus groups were held (n = 41). The main themes that emerged from the discussions were the passive role of users in decisions and delegated decision-making, based on their trust in the health professional. Users' passive role limits their opportunities for participation in clinical decision-making, ceding power to the health professional. However, establishing a therapeutic partnership allows users to feel that they are being treated as unique individuals whom the professional listens to and respects, ensuring that the decisions of the health team can be trusted, since they look out for the users' real interests. CONCLUSION: Users' participation in clinical encounters is still limited in Chile. However, bolstering that participation is essential for increasing user satisfaction and promoting people-centered care.

OBJETIVO: Descrever a experiência de participação nas decisões clínicas dos usuários dos Centros de Saúde Familiar (CESFAM) de atenção primária à saúde. MÉTODOS: Estudo qualitativo descritivo conduzido em grupos de discussão formados por usuários dos CESFAM da região sudeste da cidade de Santiago, no Chile. Foi realizada uma análise temática das informações com o uso do programa de software ATLAS.ti® versão 6. RESULTADOS: Foram formados cinco grupos de discussão (n = 41). Os principais tópicos abordados foram o papel passivo dos usuários nas decisões e a tomada de decisão delegada aos profissionais na base da confiança. O papel passivo restringe as oportunidades de participação dos usuários nas decisões clínicas e mantém o poder nas mãos dos profissionais da saúde. Apesar disso, ao ser criada uma aliança terapêutica, os usuários se sentem tratados como indivíduos únicos que são ouvidos e respeitados pelos profissionais, o que assegura que as decisões tomadas pela equipe de saúde sejam confiáveis porque protegem os reais interesses dos usuários. CONCLUSÃO: Os usuários ainda têm pouca participação nas interações clínicas no Chile. Porém, é fundamental reforçar esta participação para melhorar a satisfação do usuário e promover uma atenção mais centrada na pessoa.

[Training and competencies for primary care teams from the perspective of Chilean expertsTreinamento e competências para equipes de atenção primária na perspectiva de especialistas chilenos]. / Formación y competencias para los equipos de atención primaria desde la mirada de expertos chilenos.

OBJECTIVE: To describe the competencies for primary health care teams (PHC) in different topics related to the direct care of the user and the management of primary health centers, according to the perception of Chilean experts in PHC. METHODS: Mixed design studio. An electronic Delphi method was conducted with 29 national experts in APS. RESULTS: A matrix of specific competences related to direct work with families and to the management of the health center prioritized in three levels is proposed. Experts agreed that a critical mass of professionals with competencies in PHC is required. CONCLUSIONS: The challenge of reorganizing health systems around a strong and quality PHC can only be achieved with the participation of professionals who understand and practice the attributes and fundamental principles of PHC. The results of this study show a competency profile for PHC professionals aligned with international recommendations achievable through continuous education strategies.

OBJETIVO: Descrever as habilidades para equipes de atenção primária à saúde (APS) sobre vários tópicos vinculados com a atenção direta do usuário e gestão de centros de saúde, de acordo com a percepção de especialistas chilenos na APS. MÉTODOS: Estudo de desenho misto. Foi realizado um Delphi eletrônico com 29 especialistas nacionais em APS. RESULTADOS: É proposta uma matriz de competências específicas vinculada ao trabalho direto com famílias e à gestão do centro de saúde priorizados em três níveis. Os especialistas concordam que se requer uma massa crítica de profissionais que contem com competências em APS. CONCLUSÕES: O desafio de reorganizar os sistemas de saúde em torno de uma APS forte e de qualidade só se pode conseguir com a participação de profissionais que entendem e pratiquem os atributos e os princípios fundamentais da APS. Os resultados deste estudo mostram um perfil de competências para profissionais de APS alinhados com recomendações internacionais que podem ser alcançadas através de estratégias de educação contínua.

[Perception of users about an Integral Model of Family and Community Health care in Santiago, Chile]. / Principios orientadores del Modelo Integral de Salud Familiar y Comunitario desde la perspectiva de los usuarios.

BACKGROUND: The integral Model of Family and Community Health care is based on three essential principles: patient centered care, comprehensive care and continuity of care. AIM: To know the perception of primary care clinic users about the elements that should be considered in a patient centered integrated health care. MATERIAL AND METHODS: Ten males and 31 females aged 18 to 78 years, users of two public family primary care centers participated in focus groups, which were recorded. A qualitative descriptive research design based on content analysis according to Krippendorf was done. RESULTS: Seven issues emerged from the description of patients’ experiences: professional-patient relationship, fragmentation of care, continued care with the same professional, promotion and prevention, availability of services and patient records. CONCLUSIONS: There are difficulties to install an integral model of family and community health care. The concerns raised by participants should be considered in order to modify the design of these models.

[Access to cholecystectomy among patients attended at primary family health centers]. / Acceso a colecistectomía en un programa de tamizaje ecográfico de colelitiasis en centros de medicina familiar.

BACKGROUND: Cholelithiasis (CL) represents a major health burden in Chile, with rates of cholecystectomy (CCT) of ~40.000 per year. The explicit health care guaranties (GES) program includes prioritized CCT for CL carriers between 35 and 49 years of age. AIM: To assess the access and opportunity of CCT in a screening program of CL in Family Medicine Centers, according to the age of the patients. MATERIAL AND METHODS: A systematic ultrasound screening program of CL was developed in Family Medicine Centers ANCORA-UC between March 2009 and March 2013 during which 1.450 individuals were assessed, (80% women) and 281 were identified as having CL (19.4%). After a minimum follow up interval of six months, patients with CL were contacted and surveyed by phone. They were categorized as being beneficiaries of the GES program (those aged between 35 to 49 years) or not (those aged < 35 o > 49 years). RESULTS: Two hundred thirteen patients were contacted (76%), 81 beneficiaries of the program and 132 non-beneficiaries. The attending physician indicated CCT to 191 patients (89.6%). During a mean follow-up time of 641 days/person, 100 patients had CCT, 11% of which were emergency interventions due to complications. A greater proportion of program beneficiaries than non-beneficiaries had an elective CCT (74 and 21% respectively). The waiting interval for elective CCT was longer in non-beneficiaries compared with beneficiaries (340 ± 247 and 229 ± 201 days respectively). Only 46% of the elective CCT in GES patients were done within deadlines determined by the program (≤ 150 days). CONCLUSIONS: The age of patients at the moment of CL diagnosis conditions the access and opportunity to CCT. Beneficiaries of the explicit health care guaranties program have higher rates of cholecystectomy with less waiting time.

In situ building of a nanoprobe based on fluorescent carbon dots for methylmercury detection.

A new fluorescent assay based on in situ ultrasound-assisted synthesis of carbon dots (CDs) as optical nanoprobes for the detection of methylmercury has been developed. Application of high-intensity sonication allows simultaneous performance of the synthesis of fluorescent CDs within the analytical time scale and the selective recognition of the target analyte. Microvolume fluorospectrometry is applied for measurement of the fluorescence quenching caused by methylmercury. The assay uses low amounts of organic precursors (fructose, poly(ethylene glycol), and ethanol) and can be accomplished within 1 min. A detection limit of 5.9 nM methylmercury and a repeatability expressed as a relative standard deviation of 2.2% (N = 7) were obtained. CDs displayed a narrow size distribution with an average size of 2.5 nm as determined by electron transmission microscopy. To study the quenching mechanism, fluorescence, atomic absorption spectrometry, and Fourier transform infrared spectrometry were applied. Hydrophobicity of methylmercury and its ability to facilitate a nonradiative electron/hole recombination are suggested as the basis of the recognition event. A simple and green assay is achieved for quick detection of methylmercury without the use of tedious sample preparation procedures or complex and expensive instrumentation.

A Novel Pathogenic Variant in the MN1 Gene in a Patient Presenting with Rhombencephalosynapsis and Craniofacial Anomalies, Expanding MN1 C-terminal Truncation Syndrome.

Meningioma-1 is a transcription activator that regulates mammalian palate development and is required for appropriate osteoblast proliferation, motility, differentiation, and function. Microdeletions involving the MN1 gene have been linked to syndromes including craniofacial anomalies, such as Toriello-Carey syndrome. Recently, truncating variants in the C-terminal portion of the MN1 transcriptional factor have been linked to a characteristic and distinct phenotype presenting with craniofacial anomalies and partial rhombencephalosynapsis, a rare brain malformation characterized by midline fusion of the cerebellar hemispheres with partial or complete loss of the cerebellar vermis. It has been called MN1 C-terminal truncation (MCTT) syndrome or CEBALID (Craniofacial defects, dysmorphic Ears, Brain Abnormalities, Language delay, and Intellectual Disability) and suggested to be caused by dominantly acting truncated protein MN1 instead of haploinsufficiency. As a proto-oncogene, MN1 is also involved in familial meningioma. In this study, we present a novel case of MCTT syndrome in a female patient presenting with craniofacial anomalies and rhombencephalosynapsis, harboring a de novo pathogenic variant in the MN1 gene: c.3686_3698del, p.(Met1229Argfs*87).

Quantum dots confined in an organic drop as luminescent probes for detection of selenium by microfluorospectrometry after hydridation: study of the quenching mechanism and analytical performance.

Following a preliminary work (Costas-Mora, I.; Romero, V.; Pena-Pereira, F.; Lavilla, I.; Bendicho, C. Anal. Chem.2011, 83, 2388-2393), a quenching mechanism has been established for the selective detection of Se (as selenium hydride) by microfluorospectrometry using CdSe quantum dots (QDs) as luminescent probes stabilized with hexadecylamine and confined in an organic droplet. For this purpose, luminescence, luminescence lifetime, UV-vis absorption, total reflection X-ray fluorescence, transmission electron microscopy, and atomic force microscopy measurements were performed. The presence of stabilizing agents of QDs in the droplet was found to cause a critical effect on both extraction efficiency of selenium hydride in the drop and luminescence quenching. A self-quenching mechanism due to the aggregation of QDs is suggested. Aggregation is thought to occur as a result of the binding between selenide trapped into the organic drop as selenium hydride and Cd(2+) present in the surface of QDs, which in turn, may cause the loss of stabilizing hexadecylamine groups. After full optimization of main variables influencing the luminescent response, the analytical performance was established. A detection limit as low as 0.08 µg L(-1) Se(IV) and a repeatability expressed as relative standard deviation of 4.6% were obtained. The method was validated against CRM NWTM-27.2 lake water, and a recovery study was performed with synthetic seawater. The use of CdSe as luminescent probes in an organic drop may constitute an extremely selective, sensitive, and miniaturized assay for in situ detection of Se(IV) in water.

Casiopeina II-gly and bromo-pyruvate inhibition of tumor hexokinase, glycolysis, and oxidative phosphorylation.

The copper-based drug Casiopeina II-gly (CasII-gly) shows potent antineoplastic effect and diminishes mitochondrial metabolism on several human and rodent malignant tumors. To elucidate whether CasII-gly also affects glycolysis, (a) the flux through the complete pathway and the initial segment and (b) the activities of several glycolytic enzymes of AS-30D hepatocarcinoma cells were determined. CasII-gly (IC50 = 0.74-6.7 µM) was more effective to inhibit 24-72 h growth of several human carcinomas than 3-bromopyruvate (3BrPyr) (IC50 = 45-100 µM) with no apparent effect on normal human-proliferating lymphocytes and HUVECs. In short-term 60-min experiments, CasII-gly increased tumor cell lactate production and glycogen breakdown. CasII-gly was 1.3-21 times more potent than 3BrPyr and cisplatin to inhibit tumor HK. As CasII-gly inhibited the soluble and mitochondrial HK activities and the flux through the HK-TPI glycolytic segment, whereas PFK-1, GAPDH, PGK, PYK activities and HPI-TPI segment flux were not affected, the data suggested glycogenolysis activation induced by HK inhibition. Accordingly, glycogen-depleted as well as oligomycin-treated cancer cells became more sensitive to CasII-gly. The inhibition time-course of HK by CasII-gly was slower than that of OxPhos in AS-30D cells, indicating that glycolytic toxicity was secondary to mitochondria, the primary CasII-gly target. In long-term 24-h experiments with HeLa cells, 5 µM CasII-gly inhibited OxPhos (80%), glycolysis (40%), and HK (42%). The present data indicated that CasII-gly is an effective multisite anticancer drug simultaneously targeting mitochondria and glycolysis.

Naturally occurring deamidated triosephosphate isomerase is a promising target for cell-selective therapy in cancer.

Human triosephosphate isomerase (HsTIM) is a central glycolytic enzyme and is overexpressed in cancer cells with accelerated glycolysis. Triple-negative breast cancer is highly dependent on glycolysis and is typically treated with a combination of surgery, radiation therapy, and chemotherapy. Deamidated HsTIM was recently proposed as a druggable target. Although thiol-reactive drugs affect cell growth in deamidated HsTIM-complemented cells, the role of this protein as a selective target has not been demonstrated. To delve into the usefulness of deamidated HsTIM as a selective target, we assessed its natural accumulation in breast cancer cells. We found that deamidated HsTIM accumulates in breast cancer cells but not in noncancerous cells. The cancer cells are selectively programmed to undergo cell death with thiol-reactive drugs that induced the production of methylglyoxal (MGO) and advanced glycation-end products (AGEs). In vivo, a thiol-reactive drug effectively inhibits the growth of xenograft tumors with an underlying mechanism involving deamidated HsTIM. Our findings demonstrate the usefulness of deamidated HsTIM as target to develop new therapeutic strategies for the treatment of cancers and other pathologies in which this post translationally modified protein accumulates.

Quantum dot-based headspace single-drop microextraction technique for optical sensing of volatile species.

Core-shell CdSe/ZnS quantum dots (QDs) dispersed in a droplet of organic solvent have been applied for the first time as luminescent probes for the selective detection of volatile species. Luminescence quenching caused by volatile species was examined after their trapping onto a drop using the headspace single-drop microextraction (HS-SDME) approach along with microvolume fluorospectrometry. The novel method is characterized by low reagent and sample consumption, especially regarding QDs, a reduction about 500-fold for each analysis being attained in comparison with luminescent probing in aqueous phase using conventional luminescence spectrometers with 1 cm quartz cells for measurement. To assess QDs as luminescent probes along with HS-SDME, 14 volatile species were tried. Strong luminescence quenching (i.e., I(0)/I > 2.5) was observed for species such as CH(3)Hg(+) and Se(IV) after hydridation with NaBH(4). Moderate luminescent quenching (I(0)/I ≈ 2) was observed for species such as Hg(II) after its conversion into Hg(0), H(2)S, and methylcyclopentadienyl-manganese tricarbonyl (MMT). Small luminescence quenching effects (i.e., 1< I(0)/I <2) were caused by other hydride forming species such as As(III), Sb(III), Te(IV), and Bi(III), as well as SnBu(4), volatile amines, and endosulfan. Detection limits of 6.3 × 10(-9) and 1.6 × 10(-7) M were obtained for Se(IV) and CH(3)Hg(+), respectively. Repeatability expressed as relative standard deviation (N = 7) was about 5%. QD-HS-SDME-µvolume-fluorospectrometry allows one to carry out matrix separation, preconcentration, and confinement of QDs, hence achieving a selective, sensitive, fast, environmentally friendly, and miniaturized luminescence assay.

Antimicrobial peptide genes in Bacillus strains from plant environments.

The presence of the antimicrobial peptide (AMP) biosynthetic genes srfAA (surfactin), bacA (bacylisin), fenD (fengycin), bmyB (bacyllomicin), spaS (subtilin), and ituC (iturin) was examined in 184 isolates of Bacillus spp. obtained from plant environments (aerial, rhizosphere, soil) in the Mediterranean land area of Spain. Most strains had between two and four AMP genes whereas strains with five genes were seldom detected and none of the strains had six genes. The most frequent AMP gene markers were srfAA, bacA, bmyB, and fenD, and the most frequent genotypes srfAA-bacA-bmyB and srfAAbacA- bmyB-fenD. The dominance of these particular genes in Bacillus strains associated with plants reinforces the competitive role of surfactin, bacyllomicin, fengycin, and bacilysin in the fitness of strains in natural environments. The use of these AMP gene markers may assist in the selection of putative biological control agents of plant pathogens.

Coordination compounds with heterocyclic ester derivatives. Structural characterization and anti-proliferative activity.

A series of new coordination compounds of cobalt(II), copper(II) and zinc(II) with heterocyclic ester derivatives (ethyl 4-methyl-5-imidazole-carboxylate (emizco), 1-(2-(phenylsulphonyl)ethyl)-4-imidazole carboxylate (semizco)) and methyl 5-(propylthio)-2-benzimidazolecarbamate (albendazole, abz) were synthesized. They were fully characterized by different techniques such as IR, UV-Vis-NIR, elemental analysis, molar conductivity and magnetic susceptibility. Additionally, X-ray crystal structures of semizco and its [Co(semizco)2Cl2]·2CH3CN 10, [Co(smmizco)2Br2]·2CH3CN 11 and [Cu(semizco)2Br2] 15 coordination compounds are analyzed. These compounds present lone pair SO⋯π interactions between the sulfone and the imidazolic ring. These ligands showed three coordination modes: monodentate, through an imidazolic nitrogen atom, or a bidentate chelating mode by a nitrogen and an oxygen atom from the ester group. The different coordination modes and the number of coordinated ligands gave rise to tetrahedral and octahedral compounds, or for [Cu(semizco)(µ-Br)Br]n·0.5H2O 7 a square base pyramidal geometry. A cytotoxic study was carried out with the free ligands and their copper(II) and zinc(II) halide coordination compounds on HeLa (cervix-uterine), MCF-7 (breast), HCT-15 (colon), PC3 (prostate) human carcinoma cell lines and L929 mouse fibroblast (healthy cells). A TUNEL assay (terminal deoxynucleotidyl transferase dUTP nick end labeling) was performed with the most active copper(II) compounds to determine if cell death was by apoptosis.