Negative regulation of transcription factors by Srb10 cyclin-dependent kinase

The ubiquitin-dependent proteolytic pathway plays an important role in a broad array of cellular processes, inducting cell cycle control and transcription. Biochemical analysis of the ubiquitination of Sic1, the B-type cyclin-dependent kinase (CDK) inhibitor in budding yeast helped to define a ubiquitin ligase complex named SCF^cdc4 (for Skp1, Cdc53/cullin, F-box protein). We found that besides Sic1, the CDK inhibitor Far1 and the replication initiation protein Cdc6 are also substrates of SCF^cdc4 in vitro. A common feature in the ubiquitination of the cell cycle SCF^cdc4 substrates is that they must be phosphorylated by the major cell cycle CDK, Cdc28. Gcn4, a transcription activator involved in the general control of amino acid biosynthesis, is rapidly degraded in an SCF^cdc4-dependent manner in vivo. We have focused on this substrate to investigate the generality of the SCF^cdc4 pathway. Through biochemical fractionations, we found that the Srb10 CDK phosphorylates Gcn4 and thereby marks it for recognition by SCF^cdc4 ubiquitin ligase. Srb10 is a physiological regulator of Gcn4 stability because both phosphorylation and turnover of Gcn4 are diminished in srb10 mutants. Furthermore, we found that at least two different CDKs, Pho85 and Srb10, conspire to promote the rapid degradation of Gcn4 in vivo. The multistress response transcriptional regulator Msn2 is also a substrate for Srb10 and is hyperphosphorylated in an Srb10-dependent manner upon heat stress-induced translocation into the nucleus. Whereas Msn2 is cytoplasmic in resting wild type cells, its nuclear exclusion is partially compromised in srb10 mutant cells. Srb10 has been shown to repress a subset of genes in vivo, and has been proposed to inhibit transcription via phosphorylation of the C-terminal domain of RNA polymerase II. Our results suggest a general theme that Srb10 represses the transcription of specific genes by directly antagonizing the transcriptional activators.

Dissecting neural circuits for vision in nonhuman primates using fMRI-guided electrophysiology and optogenetics

The visual system is a remarkable platform that evolved to solve difficult computational problems such as detection, recognition, and classification of objects. Of great interest is the face-processing network, a sub-system buried deep in the temporal lobe, dedicated for analyzing specific type of objects (faces). In this thesis, I focus on the problem of face detection by the face-processing network. Insights obtained from years of developing computer-vision algorithms to solve this task have suggested that it may be efficiently and effectively solved by detection and integration of local contrast features. Does the brain use a similar strategy? To answer this question, I embark on a journey that takes me through the development and optimization of dedicated tools for targeting and perturbing deep brain structures. Data collected using MR-guided electrophysiology in early face-processing regions was found to have strong selectivity for contrast features, similar to ones used by artificial systems. While individual cells were tuned for only a small subset of features, the population as a whole encoded the full spectrum of features that are predictive to the presence of a face in an image. Together with additional evidence, my results suggest a possible computational mechanism for face detection in early face processing regions. To move from correlation to causation, I focus on adopting an emergent technology for perturbing brain activity using light: optogenetics. While this technique has the potential to overcome problems associated with the de-facto way of brain stimulation (electrical microstimulation), many open questions remain about its applicability and effectiveness for perturbing the non-human primate (NHP) brain. In a set of experiments, I use viral vectors to deliver genetically encoded optogenetic constructs to the frontal eye field and faceselective regions in NHP and examine their effects side-by-side with electrical microstimulation to assess their effectiveness in perturbing neural activity as well as behavior. Results suggest that cells are robustly and strongly modulated upon light delivery and that such perturbation can modulate and even initiate motor behavior, thus, paving the way for future explorations that may apply these tools to study connectivity and information flow in the face processing network.

Fish diversity of the wild and aquaculture water bodies in Singida Region

Tanzania Fisheries Research Institute being currently the only fisheries research institute in Tanzania has sole responsibility of marking the presence and distribution of fish species in the country. This work is expected to be completed by the year 2005. In order that this work can be accomplished, both published works and field observations (including geographical location using GPS) have to be compiled. Since the institute has centers in all the Great Lakes and one along the Indian Ocean coast, it is expected that field observations and identifications will be obtained and incorporated into the document to be produced by 2005. (PDF contains 15 pages)

The meaning of some common terms used in sampling toxic phytoplankton

The author explains some aspects of sampling phytoplankton blooms and the evaluation of results obtained from different methods. Qualitative and quantitative sampling is covered as well as filtration, freeze-drying and toxin separation.

Densidade, genética e saúde populacional como ferramentas para propor um plano de controle e erradicação de invasão biológica: o caso de Callithrix aurita (Primates) no Parque Nacional da Serra dos Órgãos, RJ, Brasil

A introdução de espécies em locais fora de sua distribuição natural é uma preocupação importante na conservação da biodiversidade. A espécie Callithrix aurita é endêmica das regiões de floresta de altitude da Mata Atlântica do Sudeste do Brasil. Os critérios mais relevantes que a enquadram como espécie ameaçada de extinção são: destruição do habitat, incapacidade de adaptação a florestas secundárias degradadas, declínio populacional, distribuição restrita e introdução de espécies exóticas invasoras. Estes critérios, aliados à evidente raridade, explicam a sua inclusão na Lista Oficial de Espécies da Fauna Brasileira Ameaçadas de Extinção. Os objetivos do trabalho são: estimar o tamanho populacional de C. aurita, C. penicillata e seus híbridos no Parque Nacional da Serra dos Órgãos, avaliar a hibridação entre as espécies por caracteres morfológicos e laboratoriais, verificar o estado de saúde e confirmar a participação de C. aurita na paternidade dos animais capturados, propor um plano de erradicação e de controle de invasão de C. penicillata no Parque. Os tamanhos populacionais das duas espécies de primatas foram estimados através do método Distance Sampling. Um total de sete sagüis foi capturado com armadilhas de captura viva para a contenção física e química e posterior realização dos procedimentos. Para o hemograma, as dosagens bioquímicas e as análises genéticas, o sangue foi recolhido em um tubo de ensaio contendo anticoagulante e mantido em temperatura de refrigeração até o momento da manipulação / processamento das amostras. Callithrix aurita parece estar bem preservada apenas na área do Parque correspondente ao trecho situado no município de Petrópolis. As análises citogenéticas e moleculares dos híbridos são uma ferramenta útil para confirmar se há ou não hibridação, identificando as espécies envolvidas e verificando se há tendência nos retrocruzamentos. Pode-se sugerir que existe uma tendência à diferenciação das espécies e identificação de indivíduos híbridos pelo padrão hematológico e bioquímico, a ser confirmada com uma amostragem maior de animais da espécie C. aurita, preferencialmente da mesma localidade e nas mesmas condições. No caso de C. aurita, as principais recomendações para sua conservação incluem pesquisas para o registro de outras populações em áreas de distribuição livres de invasão, para que se possa avaliar as chances de recuperação populacional e sobrevivência da espécie. A criação de novas Unidades de Conservação deve ser estimulada, assim como estudos mais aprofundados sobre a espécie nos locais já conhecidos de ocorrência, além de um programa seguro de criação em cativeiro.

Use of Artificial Eelgrass Mats by Saltmarsh-Nesting Common Terns (Sterna hirundo)

Terns and skimmers nesting on saltmarsh islands often suffer large nest losses due to tidal and storm flooding. Nests located near the center of an island and on wrack (mats of dead vegetation, mostly eelgrass Zostera) are less susceptible to flooding than those near the edge of an island and those on bare soil or in saltmarsh cordgrass (Spartina alterniflora). In the 1980’s Burger and Gochfeld constructed artificial eelgrass mats on saltmarsh islands in Ocean County, New Jersey. These mats were used as nesting substrate by common terns (Sterna hirundo) and black skimmers (Rynchops niger). Every year since 2002 I have transported eelgrass to one of their original sites to make artificial mats. This site, Pettit Island, typically supports between 125 and 200 pairs of common terns. There has often been very little natural wrack present on the island at the start of the breeding season, and in most years natural wrack has been most common along the edges of the island. The terns readily used the artificial mats for nesting substrate. Because I placed artificial mats in the center of the island, the terns have often avoided the large nest losses incurred by terns nesting in peripheral locations. However, during particularly severe flooding events even centrally located nests on mats are vulnerable. Construction of eelgrass mats represents an easy habitat manipulation that can improve the nesting success of marsh-nesting seabirds.

A common axiom for classical division rules for claims problems

In this paper we introduce a new axiom, denoted claims separability, that is satisfied by several classical division rules defined for claims problems. We characterize axiomatically the entire family of division rules that satisfy this new axiom. In addition, employing claims separability, we characterize the minimal overlap rule, given by O'Neill (1982), Piniles rule and the rules in the TAL-family, introduced by Moreno-Ternero and Villar (2006), which includes the uniform gains rule, the uniform losses rule and the Talmud rule.

Do sertão à zona rural. Que sertão?

Sertão se apresenta no imaginário comum do brasileiro como sendo uma região agreste, marcada pelo clima semi-árido e pela caatinga; além de ser descrito como uma área longe do litoral e distante das grandes povoações. Entretanto, ao estudar a história da cidade do Rio de Janeiro percebemos modificações substanciais neste conceito. Sendo assim, o objetivo desta tese foi polemizar sobre o conceito de sertão e analisar seu processo de transformação/modernização até a criação da zona oeste. Assim, ao mesmo tempo em que analisou esse processo, avaliou a relação cidade-campo e como foi compreendida em diferentes momentos no processo de formação da cidade do Rio de Janeiro e arredores.

Common Fixed Points of Generalized Rational Type Cocyclic Mappings in Multiplicative Metric Spaces

The aim of this paper is to present fixed point result of mappings satisfying a generalized rational contractive condition in the setup of multiplicative metric spaces. As an application, we obtain a common fixed point of a pair of weakly compatible mappings. Some common fixed point results of pair of rational contractive types mappings involved in cocyclic representation of a nonempty subset of a multiplicative metric space are also obtained. Some examples are presented to support the results proved herein. Our results generalize and extend various results in the existing literature.

Coincidence and common fixed point theorems for Suzuki type hybrid contractions and applications

Coincidence and common fixed point theorems for a class of Suzuki hybrid contractions involving two pairs of single-valued and multivalued maps in a metric space are obtained. In addition, the existence of a common solution for a certain class of functional equations arising in a dynamic programming is also discussed.

Avoidance of common problems on ponds and lakes.

This report looks at the events that results in fish deaths on ponds and lakes, and how to control and avoid them. Problems include de-oxygenation of the water, algal growth, water temperature, excessive fish stocks, excessive weed growth and excessive zooplankton

Current Approaches for Predicting a Lack of Response to Anti-EGFR Therapy in KRAS Wild-Type Patients

Targeting epidermal growth factor receptor (EGFR) has been one of the most effective colorectal cancer strategies. Anti-EGFR antibodies function by binding to the extracellular domain of EGFR, preventing its activation, and ultimately providing clinical benefit. KRAS mutations in codons 12 and 13 are recognized prognostic and predictive biomarkers that should be analyzed at the clinic prior to the administration of anti-EGFR therapy. However, still an important fraction of KRAS wild-type patients do not respond to the treatment. The identification of additional genetic determinants of primary or secondary resistance to EGFR targeted therapy for further improving the selection of patients is urgent. Herein, we review the latest published literature highlighting the most important genes that may predict resistance to anti-EGFR monoclonal antibodies in colorectal cancer patients. According to the available findings, the evaluation of BRAF, NRAS, PIK3CA, and PTEN status could be the right strategy to select patients who are likely to respond to anti-EGFR therapies. In the future, the combination of those biomarkers will help establish consensus that can be introduced into clinical practice.