Biosynthesis of antibiotic chuangxinmycin from

Chuangxinmycin is an antibiotic isolated from CPCC 200056 in the 1970s with a novel indole-dihydrothiopyran heterocyclic skeleton. Chuangxinmycin showed antibacterial activity and efficacy in mouse infection models as well as preliminary clinical trials. But the biosynthetic pathway of chuangxinmycin has been obscure since its discovery. Herein, we report the identification of a stretch of DNA from the genome of CPCC 200056 that encodes genes for biosynthesis of chuangxinmycin by bioinformatics analysis. The designated cluster was then confirmed to be responsible for chuangxinmycin biosynthesis by direct cloning and heterologous expressing in M1146. The cytochrome P450 CxnD was verified to be involved in the dihydrothiopyran ring closure reaction by the identification of seco-chuangxinmycin in M1146 harboring the gene cluster with an inactivated . Based on these results, a plausible biosynthetic pathway for chuangxinmycin biosynthesis was proposed, by hijacking the primary sulfur transfer system for sulfur incorporation. The identification of the biosynthetic gene cluster of chuangxinmycin paves the way for elucidating the detail biochemical machinery for chuangxinmycin biosynthesis, and provides the basis for the generation of novel chuangxinmycin derivatives by means of combinatorial biosynthesis and synthetic biology.

Effect of hydrogen bond formation/replacement on solubility characteristics, gastric permeation and pharmacokinetics of curcumin by application of powder solution technology

The present research aimed to improve the dissolution rate and bioavailability of curcumin using the potential of liquisolid technology. Twelve drug-loaded liquisolid systems (LS-1 to LS-12) were prepared using different vehicles (PEG 200, PEG 400 and Tween 80) and curcumin concentrations in vehicle (40%, 50%, 60% and 70%,/). The carrier [microcrystalline cellulose (MCC) PH102] to coat (Aerosil) ratio was 20 in all formulations. The systems were screened for pre-compression properties before being compressed to liquisolid tablets (LT-1 to LT-12). Post compression tests anddissolution of LTs were conducted and the results compared with those obtained for a directly compressed tablet (DCT) made of curcumin, MCC PH102 and Aerosil. LTs exhibited higher cumulative drug release (CDR) than the DCT and the optimum formulation, LT-9 (made using Tween 80), was studied by powder XRD, DSC, SEM and FTIR.permeation of curcumin from LT-9 through goat gastrointestinal mucosa was significantly (<0.05) enhanced and its oral bioavailability was increased 18.6-fold in New Zealand rabbits.cytotoxicity (IC) of LT-9 towards NCL 87 cancer cells was 40.2 µmol/L substantiating its anticancer efficacy. Accelerated stability studies revealed insignificant effects of temperature and humidity on LT-9. In summary, solubility enhancement of curcumin in LTs produced significant improvements in its permeation and bioavailability.

Entrenamiento en configuraciones vinculares de familia y pareja bajo la modalidad terapeuta-coterapeuta / Training in family and couple bonding configurations under the therapist-co-therapist modality

Objetivo. El estudio es del tipo investigación-intervención bajo la modalidad terapeuta-coterapeuta,orientado a entrenar a los/as estudiantes, en atención a familias y parejas. Método. Se utilizó la metodología cualitativa acción participante, en la vertiente llamada experiencial. Participaron en el estudio dos profesionales, psicólogas clínicas y 6 estudiantes de pregrado de Psicología de últimos semestres. Resultados. Se recogieron las experiencias vividas mediante la fundamentación e implementación de un modelo piloto de entrenamiento a estudiantes de Psicología en atención a familias y parejas para que pudiera ser sistematizado por la Universidad. Conclusión. La implementación del modelo de atención terapeuta-coterapeuta permitió ampliar la mirada y pasar de una atención individual (intrapsíquica) a una atención familiar, grupal o de parejas (interpersonal). Se demostró cómo la co-construcción del conocimiento deriva del trabajo en grupo y cómo emerge la necesidad de implementar otros modelos de entrenamiento terapéutico a estudiantes de pregrado en Psicología para afrontar eficazmente su práctica clínica profesional.

Objective. The purpose of this study was to design a therapist - co-therapist training model, and to introduce undergraduate Psychology students to the practice of family and couples therapy and to broaden their perspective and reasoning from an individual to a relational reading of psychosocial processes. The study followed a research/intervention model. Method. The methodology was clinical and action-oriented, following an experiential approach. Two therapists coordinated the training workshops with 6 senior Psychology students. Initially a collaborative seminar was formed to study and discuss the theoretical concepts of family and couples therapy and to explore and analyze the participants' own genealogy and family tree structure. Gradually, the group became a clinical team and therapist - co-therapist pairs started diagnostic and intervention procedures. Results. Experiences through the implementation of a pilot model for introducing and training Psychology students to work with families and couples were gathered, so that these could be systematized by the program. Data from therapy sessions and staff meetings were recorded and analyzed through qualitative procedures. Conclusion. As a product of the implementation of this pilot model, the perspective of the undergraduate Psychology students was broadened from an individual (intrapsychic) focus to a group (interpersonal), family, or couples focus. The findings demonstrate how the co-construction of knowledge is derived from group work, and the need to implement other training models for the training of students in psychological reasoning for professional practice.

Escopo. O estudo foi feito usando o desenho de pesquisa- intervenção, com o que procura-se treinar estudantes de Psicologia em atenção a famílias e casais com o modelo terapeuta- coterapeuta. Metodologia. Dois profissionais, psicólogas clínicas e seis estudantes de licenciatura de Psicologia de últimos semestres participaram no estudo. Os dados foram coletados com a metodologia qualitativa ação participante, na vertente chamada experiencial. Resultados. Foram coletadas as experiências vividas mediante a fundamentação e implementação de um modelo piloto de treinamento a estudantes de Psicologia em atenção a famílias e casais para puder ser sistematizado pela universidade. Conclusão. A implementação do modelo de atenção terapeuta-coterapeuta permitiu ampliar a mirada e passar de uma atenção individual (intrapsíquica) a uma atenção familiar, grupal, o de casais (interpessoal). Foi demostrado como a co- construção do conhecimento deriva do trabalho em grupo e da qual emerge a necessidade de implementar outros modelos de treinamento terapêutico a estudantes de licenciatura em Psicologia, para afrontar eficazmente sua prática clínica profissional.

Ribosome evolution: Emergence of peptide synthesis machinery.

Proteins, the main players in current biological systems, are produced on ribosomes by sequential amide bond (peptide bond) formations between amino-acid-bearing tRNAs. The ribosome is an exquisite super-complex of RNA-proteins, containing more than 50 proteins and at least 3 kinds of RNAs. The combination of a variety of side chains of amino acids (typically 20 kinds with some exceptions) confers proteins with extraordinary structure and functions. The origin of peptide bond formation and the ribosome is crucial to the understanding of life itself. In this article, a possible evolutionary pathway to peptide bond formation machinery (proto-ribosome) will be discussed, with a special focus on the RNA minihelix (primordial form of modern tRNA) as a starting molecule. Combining the present data with recent experimental data, we can infer that the peptidyl transferase center (PTC) evolved from a primitive system in the RNA world comprising tRNA-like molecules formed by duplication of minihelix-like small RNA.