Shared mechanism of teratogenicity of anti-angiogenic drugs identified in the chicken embryo model

This study was supported by a Wellcome Trust-NIH PhD Studentship to SB, WDF and NV. Grant number 098252/Z/12/Z. SB, CHC and WDF are supported by the Intramural Research Program, NCI, NIH. NHG and WL are supported by the Intramural Research Program, NIA, NIH.

Tissue specific regulation of sirtuin and nicotinamide adenine dinucleotide biosynthetic pathways identified in C57Bl/6 mice in response to high-fat feeding

Funding: The Scottish Government's Rural and Environment Science and Analytical Services Division.

Horta escolar: temas geradores e os momentos pedagógicos no ensino de ciências

Science application has faced problems in the process of training and cognizant thinking subjects in their actions. Thus, this work is justified in order to reorganize the contents of this area of knowledge. Thus, the research entitled "Plantation School: generating themes and teaching moments in teaching of science" was developed with a group of 6th grade of elementary school, from the planting of vegetables in tires without usefulness, with purpose of building meanings and scientific concepts to students. This work was based on sociointeractionist perspective of Vygotsky (1996, 1998), education for thematic research Freire (1983, 1996) as well as in problem-solving situations identified by the methodology of Pedagogical Moments Delizoicov and Angoti (1992; 2002 ) which together corroborated for the construction of a proposed teaching and learning, curriculum reorganization and significance of scientific concepts. Thus, the project breaks in practice with the linearity of the contents, to develop and analyze themes mediated by pedagogical moments, in order to ascertain the contribution of this methodological resource for the teacher's work, with regard to the understanding of scientific concepts by students. Thus, lesson plans were built based on the study situation "Horta School" and Themes Generators "human interaction with the environment", "photosynthesis", "Ecology and Nutrition of living beings", culminating in the work proposal developed in the classroom. From these themes, the contents were worked through pedagogical moments, which are organized into three stages: questioning, organization / systematization of knowledge and application / contextualization of knowledge. Thus, within each Theme Generator activities were planned which resulted in the involvement of students in learning scientific concepts, such as the issue of sustainability, environmental pollution, nutrition of living beings and the decomposition of organic matter. This work led and motivated student participation in Themes generators, and allows greater interaction between teacher-student and student among his peers, through dialogism established in the classroom, which promoted a more meaningful learning for students.

Functional Evaluation of Causal Mutations Identified in Human Genetic Studies

Human genetics has been experiencing a wave of genetic discoveries thanks to the development of several technologies, such as genome-wide association studies (GWAS), whole-exome sequencing, and whole genome sequencing. Despite the massive genetic discoveries of new variants associated with human diseases, several key challenges emerge following the genetic discovery. GWAS is known to be good at identifying the locus associated with the patient phenotype. However, the actually causal variants responsible for the phenotype are often elusive. Another challenge in human genetics is that even the causal mutations are already known, the underlying biological effect might remain largely ambiguous. Functional evaluation plays a key role to solve these key challenges in human genetics both to identify causal variants responsible for the phenotype, and to further develop the biological insights from the disease-causing mutations.

We adopted various methods to characterize the effects of variants identified in human genetic studies, including patient genetic and phenotypic data, RNA chemistry, molecular biology, virology, and multi-electrode array and primary neuronal culture systems. Chapter 1 is a broader introduction for the motivation and challenges for functional evaluation in human genetic studies, and the background of several genetics discoveries, such as hepatitis C treatment response, in which we performed functional characterization.

Chapter 2 focuses on the characterization of causal variants following the GWAS study for hepatitis C treatment response. We characterized a non-coding SNP (rs4803217) of IL28B (IFNL3) in high linkage disequilibrium (LD) with the discovery SNP identified in the GWAS. In this chapter, we used inter-disciplinary approaches to characterize rs4803217 on RNA structure, disease association, and protein translation.

Chapter 3 describes another avenue of functional characterization following GWAS focusing on the novel transcripts and proteins identified near the IL28B (IFNL3) locus. It has been recently speculated that this novel protein, which was named IFNL4, may affect the HCV treatment response and clearance. In this chapter, we used molecular biology, virology, and patient genetic and phenotypic data to further characterize and understand the biology of IFNL4. The efforts in chapter 2 and 3 provided new insights to the candidate causal variant(s) responsible for the GWAS for HCV treatment response, however, more evidence is still required to make claims for the exact causal roles of these variants for the GWAS association.

Chapter 4 aims to characterize a mutation already known to cause a disease (seizure) in a mouse model. We demonstrate the potential use of multi-electrode array (MEA) system for the functional characterization and drug testing on mutations found in neurological diseases, such as seizure. Functional characterization in neurological diseases is relatively challenging and available systematic tools are relatively limited. This chapter shows an exploratory research and example to establish a system for the broader use for functional characterization and translational opportunities for mutations found in neurological diseases.

Overall, this dissertation spans a range of challenges of functional evaluations in human genetics. It is expected that the functional characterization to understand human mutations will become more central in human genetics, because there are still many biological questions remaining to be answered after the explosion of human genetic discoveries. The recent advance in several technologies, including genome editing and pluripotent stem cells, is also expected to make new tools available for functional studies in human diseases.

(Table 1) Geographical location and nutrient composition of saline lake sediments (SLS) and nearby adjacent biological soil crusts (BSC) identified as potential dust sources

While microbial communities of aerosols have been examined, little is known about their sources. Nutrient composition and microbial communities of potential dust sources, saline lake sediments (SLS) and adjacent biological soil crusts (BSC), from Southern Australia were determined and compared with a previously analyzed dust sample. Multivariate analyses of fingerprinting profiles indicated that the bacterial communities of SLS and BSC were different, and these differences were mainly explained by salinity. Nutrient concentrations varied among the sites but could not explain the differences in microbial diversity patterns. Comparison of microbial communities with dust samples showed that deflation selects against filamentous cyanobacteria, such as the Nostocales group. This could be attributed to the firm attachment of cyanobacterial filaments to soil particles and/or because deflation occurs mainly in disturbed BSC, where cyanobacterial diversity is often low. Other bacterial groups, such as Actinobacteria and the spore-forming Firmicutes, were found in both dust and its sources. While Firmicutes-related sequences were mostly detected in the SLS bacterial communities (10% of total sequences), the actinobacterial sequences were retrieved from both (11-13%). In conclusion, the potential dust sources examined here show highly diverse bacterial communities and contain nutrients that can be transported with aerosols. The obtained fingerprinting and sequencing data may enable back tracking of dust plumes and their microorganisms.

Oceans Deep: Lesson B (Shark Attack)

Teacher resources for Lesson B in the Discover Oceanography 'Scheme of Work' for use in schools.

Oceans Deep: Lesson D (Mysteries of the Deep)

Teacher resources for Lesson D in the Discover Oceanography 'Scheme of Work' for use in schools.

Oceans Deep: Lesson F (Blooming algae)

Teacher resources for Lesson F in the Discover Oceanography 'Scheme of Work' for use in schools.

Oceans Deep: Lesson H (Oil Spill)

Teacher resources for Lesson H in the Discover Oceanography 'Scheme of Work' for use in schools.

Oceans Deep: Lesson E (Plankton Police)

Teacher resources for Lesson E in the Discover Oceanography 'Scheme of Work' for use in schools.

Oceans Deep: Lesson C (Floating and sinking)

Teacher resources for Lesson C in the Discover Oceanography 'Scheme of Work' for use in schools. Contains materials sourced under a CC BY SA license from the TES website.

Novel Anti-Campylobacter Compounds Identified Using High Throughput Screening of a Pre-selected Enriched Small Molecules Library

Campylobacter is a leading cause of foodborne bacterial gastroenteritis worldwide and infections can be fatal. The emergence of antibiotic-resistant Campylobacter spp. necessitates the development of new antimicrobials. We identified novel anti-Campylobacter small molecule inhibitors using a high throughput growth inhibition assay. To expedite screening, we made use of a “bioactive” library of 4,182 compounds that we have previously shown to be active against diverse microbes. Screening for growth inhibition of Campylobacter jejuni, identified 781 compounds that were either bactericidal or bacteriostatic at a concentration of 200 µM. Seventy nine of the bactericidal compounds were prioritized for secondary screening based on their physico-chemical properties. Based on the minimum inhibitory concentration against a diverse range of C. jejuni and a lack of effect on gut microbes, we selected 12 compounds. No resistance was observed to any of these 12 lead compounds when C. jejuni was cultured with lethal or sub-lethal concentrations suggesting that C. jejuni is less likely to develop resistance to these compounds. Top 12 compounds also possessed low cytotoxicity to human intestinal epithelial cells (Caco-2 cells) and no hemolytic activity against sheep red blood cells. Next, these 12 compounds were evaluated for ability to clear C. jejuni in vitro. A total of 10 compounds had an anti-C. jejuni effect in Caco-2 cells with some effective even at 25 µM concentrations. These novel 12 compounds belong to five established antimicrobial chemical classes; piperazines, aryl amines, piperidines, sulfonamide and pyridazinone. Exploitation of analogues of these chemical classes may provide Campylobacter specific drugs that can be applied in both human and animal medicine.

Options for poverty reduction through community empowerment towards sustainable fisheries resource production and equity

The current situation is that, by any measure, most fisheries worldwide are fully over exploited. This is also true of the Uganda's fisheries where the effort needed to catch fish has increased, and the average size of fish and of stocks have both declined. A productive fisheries offers many benefits: food for local consumption; raw materials for industry; employment that generates income, which in turn encourages other industrial, commercial and service activities; export markets that can be identified and met to generate hard currency, The national economy also benefits from import substitution and·opportunities for increased taxation. But for fisheries to be productive it is not enough to produce, products must be marketed. Fishers have to learn the lesson that it is no longer enough to expect production to drive the market; success will come from producing what the market demands. It is hoped that co-management can play a big role in harnessing the various energies for sustainable development and management of the fisheries resources.

Dimensão intercultural da linguagem não-verbal em contexto de sala de aula: um estudo com uma turma de espanhol

O presente relatório tem como principal objetivo desenvolver a competência da interculturalidade no âmbito da linguagem não-verbal de alunos portugueses, do 3º ciclo do ensino básico, com frequência à disciplina de Espanhol. A Linguagem não-verbal tem um contributo preponderante na comunicação e, quando há a pretensão de se conhecer outra cultura, é forçoso que se interpretem os diferentes sistemas onde cada indivíduo se integra e interage, porque comunicar eficazmente com o outro implica um conhecimento das estruturas simbólicas e dos códigos culturais intrínsecos, não só à cultura de um outro específico, mas também ao seu próprio contexto sociocultural, histórico-cultural e económico-cultural. Este trabalho faz apologia de um ensino intercultural que promova o diálogo entre culturas, sabendo-se de antemão que há representações que devem ser desconstruídas, bem como uma linguagem não-verbal específica que pode interferir na pragmática da interculturalidade. Trata-se de uma investigação-ação demarcada por dois momentos distintos: um primeiro estudo vocacionado para a consciencialização dos alunos de que a comunicação não-verbal é uma competência que se ensina e se aprende e um segundo estudo dedicado a aspetos culturais diferenciadores, entre Espanha e Portugal, na linguagem não-verbal , com enfoque nos gestos culturais e no tratamento do tempo. Os dados a analisar são: a transcrição de uma aula gravada, onde foram aplicados vários recursos audiovisuais e escritos consentâneos com as unidades programáticas, e as respostas a um questionário dirigido à turma de intervenção e a uma turma de nacionalidade espanhola que com ela colaborou. A implementação destas atividades/estratégias didáticas permitiu concluir que, por um lado, os alunos interpretam os diferentes códigos não -verbais à luz de uma perspetiva universal, por outro, há uma forte influência de estereótipos herdados e filtrados, a partir de diferentes marcos histórico-temporais. Este estudo sobre o não- verbal também se traduziu num alicerce bastante hábil para motivar à aprendizagem em geral e para enriquecer o conhecimento sobre a cultura do outro e a sua própria cultura, através da aquisição de códigos não- verbais comunicativo-funcionais.