Assessment of fight outcome is needed to activate socially driven transcriptional changes in the zebrafish brain

Group living animals must be able to express different behavior profiles depending on their social status. Therefore, the same genotype may translate into different behavioral phenotypes through socially driven differential gene expression. However, how social information is translated into a neurogenomic response and what are the specific cues in a social interaction that signal a change in social status are questions that have remained unanswered. Here, we show for the first time, to our knowledge, that the switch between status-specific neurogenomic states relies on the assessment of fight outcome rather than just on self- or opponent-only assessment of fighting ability. For this purpose, we manipulated the perception of fight outcome in male zebrafish and measured its impact on the brain transcriptome using a zebrafish whole genome gene chip. Males fought either a real opponent, and a winner and a loser were identified, or their own image on a mirror, in which case, despite expressing aggressive behavior, males did not experience either a victory or a defeat. Massive changes in the brain transcriptome were observed in real opponent fighters, with losers displaying both a higher number of differentially expressed genes and of coexpressed gene modules than winners. In contrast, mirror fighters expressed a neurogenomic state similar to that of noninteracting fish. The genes that responded to fight outcome included immediate early genes and genes involved in neuroplasticity and epigenetic modifications. These results indicate that, even in cognitively simple organisms such as zebrafish, neurogenomic responses underlying changes in social status rely on mutual assessment of fighting ability.

Transient Activation of Meox1 Is an Early Component of the Gene Regulatory Network Downstream of Hoxa2

Hox genes encode transcription factors that regulate morphogenesis in all animals with bilateral symmetry. Although Hox genes have been extensively studied, their molecular function is not clear in vertebrates, and only a limited number of genes regulated by Hox transcription factors have been identified. Hoxa2 is required for correct development of the second branchial arch, its major domain of expression. We now show that Meox1 is genetically downstream from Hoxa2 and is a direct target. Meox1 expression is downregulated in the second arch of Hoxa2 mouse mutant embryos. In chromatin immunoprecipitation (ChIP), Hoxa2 binds to the Meox1 proximal promoter. Two highly conserved binding sites contained in this sequence are required for Hoxa2-dependent activation of the Meox1 promoter. Remarkably, in the absence of Meox1 and its close homolog Meox2, the second branchial arch develops abnormally and two of the three skeletal elements patterned by Hoxa2 are malformed. Finally, we show that Meox1 can specifically bind the DNA sequences recognized by Hoxa2 on its functional target genes. These results provide new insight into the Hoxa2 regulatory network that controls branchial arch identity.

Regulador linear de tensão em tecnologia HV-CMOS

Atualmente, assiste-se na nossa sociedade a um recurso e uso massivo de equipamentos eletrónicos portáteis. Este facto, aliado à competitividade de mercado, exigiu o desenvolvimento desses equipamentos com o intuito de melhorar a sua gestão de potência e, obter, consequentemente, maior autonomia e rendimento. Assim, na gestão de potência de um SoC são os reguladores de tensão que assumem um papel de extrema importância. O trabalho realizado ao longo da presente dissertação pressupõe o projeto de um regulador linear de tensão do tipo LDO em tecnologia HV-CMOS, capaz de suportar tensões de entrada de 12V com vista à alimentação de blocos funcionais RF-CMOS com 3,3V e uma corrente de 100mA. Foi implementado através do processo CMOS de 0.35μm de 50V da Austria Micro Systems. A corrente de quiescente do regulador linear de tensão que determina a eficiência de corrente é de 120,22μA. Possui uma eficiência de corrente de 99,88% e um rendimento de 82,46% quando a tensão mínima de entrada é utilizada. O regulador linear de tensão possui uma tensão de dropout de 707mV. A estabilidade do sistema é mantida mesmo com transições de carga de 10μA para 100mA. O regulador possui um tempo de estabelecimento inferior a 2,4μs e uma variação da tensão de saída relativamente ao seu valor nominal inferior a 18mV, ambos para o pior caso. Porém, este regulador possui um undershoot e um overshoot de +- 1,85V.

Low-cost disposable ALT electrochemical microsensors for in-vitro hepatotoxic assessment

Liver-on-chip systems are widely seen as having the potential to replace animal testing for long-term liver toxicity assessments. However, such systems necessitate solutions, such as electrochemical microsensors, to provide information about the cells exposed to chemical compounds in a confined space. This study describes the development of microsensors for the detection of alanine-aminotransferase (ALT), an intracellular enzyme found in hepatocytes, for monitoring the viability of in-vitro hepatic cell cultures. The electrochemical sensors were developed by using screen printed electrodes functionalized by drop-casting. These technologies are intended to produce disposable and low-cost sensors that can easily be exchanged once their performance is degraded. The sensors are capable of measuring ALT in a microfluidic environment through the detection of changes in glutamate concentration. The microsensors were found to be stable for more than 60 days and were successfully tested using hepatocellular lysates to assess their capability to quantify ALT activity in a hepatic cell culture. These results open the way to their integration in liver bioreactors to assess hepatocellular toxicity in-vitro.

Age control and stratigraphy of a sediment profile from the Lomonosov Ridge, Arctic Ocean

The upper 200 m of the sediments recovered during IODP Leg 302, the Arctic Coring Expedition (ACEX), to the Lomonosov Ridge in the central Arctic Ocean consist almost exclusively of detrital material. The scarcity of biostratigraphic markers severely complicates the establishment of a reliable chronostratigraphic framework for these sediments, which contain the first continuous record of the Neogene environmental and climatic evolution of the Arctic region. Here we present profiles of cosmogenic 10Be together with the seawater-derived fraction of stable 9Be obtained from the ACEX cores. The down-core decrease of 10Be/9Be provides an average sedimentation rate of 14.5 ± 1 m/Ma for the uppermost 151 m of the ACEX record and allows the establishment of a chronostratigraphy for the past 12.3 Ma. The age-corrected 10Be concentrations and 10Be/9Be ratios suggest the existence of an essentially continuous sea ice cover over the past 12.3 Ma.

1975 University of Michigan Football Team

1976 University of Michigan Football Team

1977 University of Michigan Football Team

1978 University of Michigan Football Team

1979 University of Michigan Football Team

University of Michigan Men's Tennis Team, 1986

Front Row: John Solik, Franz Geiger, Hugh Kwok, Jim Sharton, Chip McColl, Mike Pizzutello, Chris Colwell

Back Row: assistant coach Mark Mees, Ed Filer, Jed Hakken, Jon Morris, John Royer, Dan Goldberg, Brad Koontz, head coach Brian Eisner

1965 Men's Gymnastics Team,

Front Row: Cliff Chilvers, coach Newt Loken, Dr. Earl Ziegler, Gary Erwin, John Hamilton, Chip Fuller, Phil Fuller,

Back Row: Rich Blanton, Mike Henderson, Ken Williams, Dick Stone, Chris Vanden Broek, John Cashman, Gary VanderVoort, Art Bassler, Fred Sanders

Not in photo: Ned Duke