Push-pull organic dyes and dye-catalyst assembly featuring a benzothiadiazole unit for photoelectrochemical hydrogen production.

In this work, we report the design and the preparation of two new dyes and a molecular dyad for the photoelectrochemical hydrogen production from water in a dye-sensitized photoelectrochemical cell (DSPEC). We designed dyes that include a benzothiadiazole (BTD) and an indacenodithiophene (IDT) units, and we obtained a new molecular dyad by covalent coupling with the cobalt diimine-dioxime catalyst. The introduction of the benzothiadiazole core in the structure improves the absorption properties and leads to an extension of the spectrum in the visible range up to 650 nm. The photoelectrochemical properties of the new dyad were evaluated on pristine and lithium-doped NiO electrodes. We demonstrate that increasing the light harvesting efficiency of the dyad by introducing a IDT-BTD chromophore is clearly beneficial for the photoelectrochemical activity. We also demonstrate that lithium doping of NiO, which improves the electronic conductivity of the mesoporous film, leads to a significant increase in performance, in terms of TON and F.E., more than doubled with our new dyad. This BTD-based molecular system outperforms the results of previously reported dyads using the same catalyst.

Self-assembly of porphyrin-DNA hybrids into large flat nanostructures.

The main aim of nanotechnology is to create functional systems by controlling the matter at the nanometer level. In this context DNA is a versatile building block for the fabrication of micrometer-scale objects with a subnanometer-scale resolution. Over the last 15 years, DNA nanotechnology has considerably developed with the invention of DNA origami, double crossover structures and molecule/oligonucleotide hybrids. Our interest is focused on the combination of short complementary DNA sequences with organic molecules with a view to create large self-assembled nanostructures. Here we report on the synthesis of porphyrin derivatives bearing up to four 21-mer oligonucleotides and we demonstrate that the combination of the molecular hybrids containing complementary DNA strands leads to the formation of large nanostructures with micrometer-scale size.

Genomic prediction models for grain yield of spring bread wheat in diverse agro-ecological zones.

Genomic and pedigree predictions for grain yield and agronomic traits were carried out using high density molecular data on a set of 803 spring wheat lines that were evaluated in 5 sites characterized by several environmental co-variables. Seven statistical models were tested using two random cross-validations schemes. Two other prediction problems were studied, namely predicting the lines' performance at one site with another (pairwise-site) and at untested sites (leave-one-site-out). Grain yield ranged from 3.7 to 9.0 t ha(-1) across sites. The best predictability was observed when genotypic and pedigree data were included in the models and their interaction with sites and the environmental co-variables. The leave-one-site-out increased average prediction accuracy over pairwise-site for all the traits, specifically from 0.27 to 0.36 for grain yield. Days to anthesis, maturity, and plant height predictions had high heritability and gave the highest accuracy for prediction models. Genomic and pedigree models coupled with environmental co-variables gave high prediction accuracy due to high genetic correlation between sites. This study provides an example of model prediction considering climate data along-with genomic and pedigree information. Such comprehensive models can be used to achieve rapid enhancement of wheat yield enhancement in current and future climate change scenario.

Carcinoma Seroso Papilar Peritoneal Primario: serie de casos Hospital Clínico Universidad de Chile 2010-2015 / Primary Serous Papillary Carcinoma: Case Report, Hospital Clinico Universidad de Chile 2010-2015

Los cánceres peritoneales primarios son una patología de baja prevalencia, dentro de los cuales el carcinoma seroso papilar primario de peritoneo es el más frecuente con una incidencia de 6,78 casos por millón de habitantes. Predomina en el sexo femenino y su principal diagnóstico diferencial es el carcinoma papilar seroso de ovario avanzado, para lo cual la inmunohistoquímica, junto a sus clasificaciones clínicas y anatomopatológicas son la forma de diferenciar en base a la clasificación de la Organización Mundial de la salud para lesiones tumorales. Objetivo: Describir los resultados inmuno-histoquímicos de una serie de casos estudiados en el Hospital Clinico de la Universidad de Chile y compararlos con la literatura médica. Material y Método: Estudio retrospectivo, descriptivo en base a análisis de 12 biopsias entre Enero 2010 y Marzo 2015 clasificándolos según edad, sexo y registro de biopsia. Se realizó técnica histológica rutinaria además de las tinciones inmunohistoquímicas para WT1, citoqueratinas y otros reactivos de acuerdo a los diagnósticos diferenciales. Resultados: La distribución etaria fue de 47 a los 75 años, media de 60 años, el 100% de los casos de sexo femenino. Los reactivos de Inmunohistoquímica predominantes fueron WT1 (53,8%), Citoqueratina-7 (38,5%). Conclusiones: Este carcinoma es una entidad poco común en la clínica, con similitudes al carcinoma seroso ovárico. Existe consenso sobre el diagnóstico de esta patología, el cual se debe orientar, según los criterios de la Gynecologic Oncology Group. Ante la sospecha clínica, el patólogo puede realizar el estudio inmunohistoquímico dirigido y así tener un diagnóstico preciso para determinar la conducta terapéutica del cirujano.

The primary peritoneal cancer is a low prevalence disease, within which primary papillary serous carcinoma of the peritoneum is the most frequent with an incidence of 6.78 cases per million inhabitants. Predominates in females and its main differential diagnosis is advanced ovarian papillary serous carcinoma, for which immunohistochemistry and clinical and pathological classifications are the way to differentiate base on the World Health Organization classification for tumor lesions. Objective: Describe the immunohistochemical results of a series of cases studied in Universidad de Chile Clinical Hospital and to compare them with the literature. Material and Methods: Descriptive retrospective study based on analysis of biopsies from 12 cases between January 2010 and March 2015 classifying them according to age, sex and biopsy register. Routine histological technique was performed in addition to the immunohistochemical staining for WT1, cytokeratin and other reagents according to the differential diagnoses. Results: The age distribution was 47 to 75 years, mean 60 years, 100% of cases female. Immunohistochemical reagents were predominant WT1 (53.8%) and cytokeratin-7 (38.5%). Conclusion: This carcinoma is a rare entity in routine clinical practice, with similarities to ovarian serous carcinoma.There is consensus on the diagnosis of this condition, which must be oriented according to the criteria of the Gynecologic Oncology Group. Clinical suspicion can lead the pathologist to perform immunohistochemical study and thus have an accurate diagnosis to determine the therapeutic approach of the surgeon.

Site-specific insertion of nitroxide-spin labels into DNA probes by click chemistry for structural analyses by ELDOR spectroscopy.

A new approach is described for the insertion of nitroxide spin-labels at specific positions within DNA oligomers. The latter bioconjugaison strategy is based on a click chemistry 1,3-dipolar cycloaddition between a spin-labeling reagent, namely the 4-azido-TEMPO, and alkyne modified uridine-containing oligonucleotides. This highly efficient labeling method was applied for site-specific incorporation of two TEMPO units within a set of double-stranded DNA constructs. Then the determination of the inter-nitroxide distances was achieved by using a four-pulses DEER technique that successfully validates the new site-directed spin labeling strategy.

Epoxide adducts at the guanine residue within single-stranded DNA chains: reactivity and stability studies.

Emphasis was placed in this work on the assessment of structural and biological features of nucleobase adducts that result from the reaction of DNA with epoxide derivatives. Thus we have prepared and characterized a set of site-specifically modified oligonucleotides at N7-position of a guanine residue, upon reaction with diepoxibutane, with the purpose of further investigating some of their biochemical features. The stability of the lesion-containing DNA fragments has also been investigated and clearly shows that the latter modified oligomers may be used as substrates for in vitro enzymatic assays, aimed at determining the biological effects within cell of these chemically induced DNA damage.

MALDI-TOF mass spectrometry as a powerful tool to study enzymatic processing of DNA lesions inserted into oligonucleotides.

MALDI-TOF mass spectrometry measurements, coupled with either exonuclease or DNA N-glycosylases digestions of lesion-containing oligonucleotides, were used to assess biochemical features of several oxidative DNA damage. The latter analytical approach was shown to be an informative and efficient alternative technique to conventional electrophoresis and chromatographic analyses.

Conformational changes of the ferric uptake regulation protein upon metal activation and DNA binding; first evidence of structural homologies with the diphtheria toxin repressor.

Fur (ferric uptake regulation protein) is a bacterial global regulator that uses iron as a cofactor to bind to specific DNA sequences. It has been suggested that metal binding induces a conformational change in the protein, which is subsequently able to recognize DNA. This mechanism of activation has been investigated here using selective chemical modification monitored by mass spectrometry. The reactivity of each lysine residue of the Fur protein was studied, first in the apo form of the protein, then after metal activation and finally after DNA binding. Of particular interest is Lys76, which was shown to be highly protected from modification in the presence of target DNA. Hydrogen-deuterium exchange experiments were performed to map with higher resolution the conformational changes induced by metal binding. On the basis of these results, together with a secondary structure prediction, the presence in Fur of a non-classical helix-turn-helix motif is proposed. Experimental results show that activation upon metal binding induces conformational modification of this specific motif. The recognition helix, interacting directly with the major groove of the DNA, would include the domain [Y55-F61]. This helix would be followed by a small "wing" formed between two beta strands, containing Lys76, which might interact directly with DNA. These results suggest that Fur and DtxR (diphtheria toxin repressor), another bacterial repressor, share not only the function of being iron concentration regulators, and the structure of their DNA-binding domain.

Characterization of an anti-Borrelia burgdorferi OspA conformational epitope by limited proteolysis of monoclonal antibody-bound antigen and mass spectrometric peptide mapping.

Lyme borreliosis is a multisystem disorder caused by the spirochete Borrelia burgdorferi that is transmitted to humans by the tick Ixodes dammini. The immune response against the 31 kDa OspA, which is one of the most abundant B. burgdorferi proteins, appears to be critical in preventing infection and tissue inflammation. Detailed knowledge of the immunological and molecular characteristics of the OspA protein is important for the development of reliable diagnostic assays. In this study, we characterized a new conformational epitope present within the middle part of B. burgdorferi OspA. Our approach used enzymatic proteolyses of the immune complex followed by mass spectrometric identification of the peptides bound to the antibody. It appears to be one of the first reports on the characterization of a discontinuous epitope using mass spectrometry.

Identification of the two zinc-bound cysteines in the ferric uptake regulation protein from Escherichia coli: chemical modification and mass spectrometry analysis.

Selective chemical modification of thiol groups combined with mass spectrometry analysis was used to characterize cysteine ligands in the zinc-binding site of the Fur protein. Fur is a metalloregulatory protein involved in the regulation of almost all bacterial genes related to iron uptake in Gram-negative bacteria such as Escherichia coli. In addition to the iron site, Fur also possesses a tight-binding zinc site that likely comprises two cysteines. Using a new procedure, we confirm the involvement of two cysteines in zinc binding and identify them within the two pairs of cysteines present in the protein. The protein was treated under nondenaturing conditions with iodoacetamide, and the progressive alkylation of the thiol groups monitored by quenching the reaction at different times and measuring the extent of alkylation by mass spectrometry. Complementary experiments were carried out in the absence or presence of EDTA, a strong zinc chelator, to determine which of the cysteines were protected from alkylation by the zinc atom. Enzymatic digestion of the modified protein and analysis of the peptide mixture by mass spectrometry enabled fast identification of reactive and protected thiol groups. Two cysteines, Cys92 and Cys95, were thus assigned as zinc ligands. Examination of the sequence comprising the zinc site indicates that it may belong to a new type of structural zinc site. Furthermore, Cys132 was shown to be the fastest reacting cysteine, implying it is a surface-exposed residue.

Efficacy and safety of oral levofloxacin compared with clarithromycin in the treatment of acute sinusitis in adults: a multicentre, double-blind, randomized study. The Canadian Sinusitis Study Group.

Adult patients with acute sinusitis (n = 236) were randomized in a double-blind study to levofloxacin 500 mg orally once daily (n = 119) or clarithromycin 500 mg orally twice daily (n = 117) for 10-14 days. Between 2 and 5 days after therapy participants were evaluated as cured (no symptoms), improved (symptoms improved, no further therapy required), or failed (further therapy required). Clinical response rates (cured plus improved) for clinically evaluable patients were 93.9% for levofloxacin (n = 98) and 93.5% for clarithromycin (n = 93). The proportion of patients evaluated as cured was higher in the levofloxacin (40.8%) than in the clarithromycin arm (29.0%) and individual symptoms showed higher rates of resolution. Of patients receiving levofloxacin and clarithromycin, 22.5% and 39.3%, respectively, experienced adverse events related or possibly related to the study therapy. This study showed that, in the treatment of acute sinusitis, daily levofloxacin therapy is as effective as twice-daily clarithromycin therapy with more complete clearing of symptoms and a more tolerable side-effect profile.

Efficacy of clarithromycin vs. amoxicillin/clavulanate in the treatment of acute maxillary sinusitis.

A new macrolide drug, clarithromycin (Biaxin) was compared with amoxicillin/clavulanate (Augmentin) in a single-blind (investigator-blind), randomized, multicenter study of 497 outpatients with acute maxillary sinusitis; treatment was 500 mg clarithromycin bid (n = 246) or 500 mg amoxicillin/clavulanate tid (n = 251). Pathogens included Streptococcus pneumoniae in 22% of patients, Staphylococcus aureus in 16%, Haemophilus influenzae in 10%, and Moraxella catarrhalis in 7%. For evaluable patients, clinical success (cure or improvement) was noted for 97% (128/132) of clarithromycin recipients and 93% (119/128) amoxicillin/clavulanate recipients. Clinically significant improvement in signs and symptoms was comparable between groups. Bacteriologic cure rates were 87% (115/132) and 90% (115/128), respectively. Respective pathogen eradication rates were 87% (125/143) and 90% (125/139). Adverse events not due to concurrent conditions occurred in 41% of the former and 46% of the latter group; most were mild to moderate gastrointestinal upsets (21% and 38%, respectively; P < 0.001). We conclude that clarithromycin appears to be as effective as amoxicillin/clavulanate in acute maxillary sinusitis and may cause fewer gastrointestinal upsets.

[Multiple primary lung cancers. The importance of early diagnosis and survival after a new surgical excision]. / Le cancer broncho-pulmonaire successif. Importance du diagnostic précoce et survie après nouvelle exérèse chirurgicale.

In a series of 1.025 consecutive resections for bronchogenic carcinoma, 68 patients developed a second primary lung cancer identified as the first site of recurrence (median interval of 38 months). Thirty-nine patients (57%) were asymptomatic (detection by chest-X-Ray (N: 28] or sputum cytology (N: 11) and 22 had one or more symptoms. A reoperation was possible in 50% (N: 34) of all patients with an operative (30 day) mortality of 14.7% (5/34) as compared to 3.5% (26/1.025) for the first procedure. Cumulative survival following the second resection was 33% at 5 years while no inoperable patient survived longer than three years. Clinical presentation of the second carcinoma is a significant prognostic variable since no symptomatic patient survived more than two years while 30% of the asymptomatic group survived 5 years (p less than 0.021).

Dietary enhancement of intestinal radioresistance during fractionated irradiation.

Rats fed laboratory chow or elemental diet 3 were given fractions of 240 rads of 60Co gamma-radiation abdominally (1200 rads/week) until all animals had died. Changes in appetite, body weight, and mortality were monitored as a function of the cumulative dose received. More radiation was needed in the diet-fed group to achieve both 0 and 100% mortality, a difference of 37% at the mean lethal dose level. Both groups developed similar progressive anorexia but the diet-fed animals lost weight more slowly. Data indicate that basic intestinal radio-resistance is enhanced by feeding the elemental diet.