1888 University of Michigan Football Team

1891 University of Michigan Football Team

Lipid-modified azurin of Neisseria meningitidis is a copper protein localized on the outer membrane surface and not regulated by FNR

The laz gene of Neisseria meningitidis is predicted to encode a lipid-modified azurin (Laz). Laz is very similar to azurin, a periplasmic protein, which belongs to the copper-containing proteins in the cupredoxin superfamily. In other bacteria, azurin is an electron donor to nitrite reductase, an important enzyme in the denitrifying process. It is not known whether Laz could function as an electron transfer protein in this important pathogen. Laz protein was heterologously expressed in Escherichia coli and purified. Electrospray mass spectrometry indicated that the Laz protein contains one copper ion. Laz was shown to be redox-active in the presence of its redox center copper ion. When oxidized, Laz exhibits an intense blue colour and absorbs visible light around 626 nm. The absorption is lost when exposed to diethyldithiocarbamate, a copper chelating agent. Polyclonal antibodies were raised against purified Laz for detecting expression of Laz under different growth conditions and to determine the orientation of Laz on the outer membrane. The expression of Laz under microaerobic and microaerobic denitrifying conditions was slightly higher than that under aerobic conditions. However, the expression of Laz was similar between the wild type strain and an fnr mutant, suggesting that Fumarate/Nitrate reduction regulator (FNR) does not regulate the expression of Laz despite the presence of a partial FNR box upstream of the laz gene. We propose that some Laz protein is exposed on the outer membrane surface of N. meningitidis as the αLaz antibodies can increase killing by complement in a capsule deficient N. meningitidis strain, in a dose-dependent fashion.

The Ectocarpus genome and the independent evolution of multicellularity in brown algae

Brown algae (Phaeophyceae) are complex photosynthetic organisms with a very different evolutionary history to green plants, to which they are only distantly related(1). These seaweeds are the dominant species in rocky coastal ecosystems and they exhibit many interesting adaptations to these, often harsh, environments. Brown algae are also one of only a small number of eukaryotic lineages that have evolved complex multicellularity (Fig. 1). We report the 214 million base pair (Mbp) genome sequence of the filamentous seaweed Ectocarpus siliculosus (Dillwyn) Lyngbye, a model organism for brown algae(2-5), closely related to the kelps(6,7) (Fig. 1). Genome features such as the presence of an extended set of light-harvesting and pigment biosynthesis genes and new metabolic processes such as halide metabolism help explain the ability of this organism to cope with the highly variable tidal environment. The evolution of multicellularity in this lineage is correlated with the presence of a rich array of signal transduction genes. Of particular interest is the presence of a family of receptor kinases, as the independent evolution of related molecules has been linked with the emergence of multicellularity in both the animal and green plant lineages. The Ectocarpus genome sequence represents an important step towards developing this organism as a model species, providing the possibility to combine genomic and genetic(2) approaches to explore these and other(4,5) aspects of brown algal biology further.

Genome-wide linkage analysis for human longevity: Genetics of healthy aging study

Clear evidence exists for heritability of humanlongevity, and much interest is focused on identifying genes associated with longer lives. To identify such longevity alleles, we performed the largest genome-wide linkage scan thus far reported. Linkage analyses included 2118nonagenarian Caucasian sibling pairs that have been enrolled in 15 study centers of 11 European countries as part of the Genetics of Healthy Aging (GEHA) project. In the joint linkage analyses, we observed four regions that show linkage with longevity; chromosome 14q11.2 (LOD = 3.47), chromosome 17q12-q22 (LOD = 2.95), chromosome 19p13.3-p13.11 (LOD = 3.76), and chromosome 19q13.11-q13.32 (LOD = 3.57). To fine map these regions linked to longevity, we performed association analysis using GWAS data in a subgroup of 1228 unrelated nonagenarian and 1907 geographically matched controls. Using a fixed-effect meta-analysis approach, rs4420638 at the TOMM40/ APOE/APOC1 gene locus showed significant association with longevity (P-value = 9.6 × 10). By combined modeling of linkage and association, we showed that association of longevity with APOEe4 and APOEe2 alleles explain the linkage at 19q13.11-q13.32 with P-value = 0.02 and P-value = 1.0 × 10, respectively. In the largest linkage scan thus far performed for human familial longevity, we confirm that the APOE locus is a longevity gene and that additional longevity loci may be identified at 14q11.2, 17q12-q22, and 19p13.3-p13.11. As the latter linkage results are not explained by common variants, we suggest that rare variants play an important role in human familial longevity.

An Evening of Opera Excerpts November 22, 23, 1971

Concert program for An Evening of Opera Excerpts, Nov 22, 23, 1971

Transformaciones discursivas en el proceso de securitización del narcotráfico. Un análisis de los actos discursivos oficiales de Colombia y Estados Unidos en la Guerra contra las drogas 1986 - 1990

El tema de las drogas suscita un debate entre quienes defienden la prohibición y la represión, y aquellos que defienden alternativas como la legalización y/o regulación y otras más moderadas como la descriminalización y la despenalización. Aunque ambas posturas muestran datos empíricos que las soportan, desde el ámbito discursivo la visión represiva se ha posicionado como la más aceptada en el continente americano, más específicamente, en Latinoamérica. El presente trabajo, hace un estudio de caso del proceso de securitización del narcotráfico entre los presidentes de Estados Unidos y Colombia durante el período 1986-1990. A lo largo del texto, se analizan discursos oficiales de los presidentes de ambos Estados, resaltando las estrategias retóricas y sus transformaciones que legitimaron acciones represivas de tipo político-militar contra las drogas. Al final se apunta a reivindicar el discurso como un instrumento para reproducir creencias sobre fenómenos, en este caso, la creencia de que las drogas son una amenaza existencial a la seguridad política y militar para los Estados.

The Phycodnaviridae: The Story of How Tiny Giants Rule the World

The family Phycodnaviridae encompasses a diverse and rapidly expanding collection of large icosahedral, dsDNA viruses that infect algae. These lytic and lysogenic viruses have genomes ranging from 160 to 560 kb. The family consists of six genera based initially on host range and supported by sequence comparisons. The family is monophyletic with branches for each genus, but the phycodnaviruses have evolutionary roots that connect them with several other families of large DNA viruses, referred to as the nucleocytoplasmic large DNA viruses (NCLDV).The phycodnaviruses have diverse genome structures, some with large regions of noncoding sequence and others with regions of ssDNA. The genomes of members in three genera in the Phycodnaviridae have been sequenced. The genome analyses have revealed more than 1000 unique genes, with only 14 homologous genes in common among the three genera of phycodnaviruses sequenced to date. Thus, their gene diversity far exceeds the number of so-called core genes. Not much is known about the replication of these viruses, but the consequences of these infections on phytoplankton have global affects, including influencing geochemical cycling and weather patterns.

Continental-scale temperature variability during the past two millennia

Past global climate changes had strong regional expression. To elucidate their spatio-temporal pattern, we reconstructed past temperatures for seven continental-scale regions during the past one to two millennia. The most coherent feature in nearly all of the regional temperature reconstructions is a long-term cooling trend, which ended late in the nineteenth century. At multi-decadal to centennial scales, temperature variability shows distinctly different regional patterns, with more similarity within each hemisphere than between them. There were no globally synchronous multi-decadal warm or cold intervals that define a worldwide Medieval Warm Period or Little Ice Age, but all reconstructions show generally cold conditions between ad 1580 and 1880, punctuated in some regions by warm decades during the eighteenth century. The transition to these colder conditions occurred earlier in the Arctic, Europe and Asia than in North America or the Southern Hemisphere regions. Recent warming reversed the long-term cooling; during the period ad 1971–2000, the area-weighted average reconstructed temperature was higher than any other time in nearly 1,400 years.

Molecular markers for urothelial bladder cancer prognosis: toward implementation in clinical practice

OBJECTIVES To summarize the current status of clinicopathological and molecular markers for the prediction of recurrence or progression or both in non-muscle-invasive and survival in muscle-invasive urothelial bladder cancer, to address the reproducibility of pathology and molecular markers, and to provide directions toward implementation of molecular markers in future clinical decision making. METHODS AND MATERIALS Immunohistochemistry, gene signatures, and FGFR3-based molecular grading were used as molecular examples focussing on prognostics and issues related to robustness of pathological and molecular assays. RESULTS The role of molecular markers to predict recurrence is limited, as clinical variables are currently more important. The prediction of progression and survival using molecular markers holds considerable promise. Despite a plethora of prognostic (clinical and molecular) marker studies, reproducibility of pathology and molecular assays has been understudied, and lack of reproducibility is probably the main reason that individual prediction of disease outcome is currently not reliable. CONCLUSIONS Molecular markers are promising to predict progression and survival, but not recurrence. However, none of these are used in the daily clinical routine because of reproducibility issues. Future studies should focus on reproducibility of marker assessment and consistency of study results by incorporating scoring systems to reduce heterogeneity of reporting. This may ultimately lead to incorporation of molecular markers in clinical practice.

Molecular and Translational Classifications of DAMPs in Immunogenic Cell Death.

The immunogenicity of malignant cells has recently been acknowledged as a critical determinant of efficacy in cancer therapy. Thus, besides developing direct immunostimulatory regimens, including dendritic cell-based vaccines, checkpoint-blocking therapies, and adoptive T-cell transfer, researchers have started to focus on the overall immunobiology of neoplastic cells. It is now clear that cancer cells can succumb to some anticancer therapies by undergoing a peculiar form of cell death that is characterized by an increased immunogenic potential, owing to the emission of the so-called "damage-associated molecular patterns" (DAMPs). The emission of DAMPs and other immunostimulatory factors by cells succumbing to immunogenic cell death (ICD) favors the establishment of a productive interface with the immune system. This results in the elicitation of tumor-targeting immune responses associated with the elimination of residual, treatment-resistant cancer cells, as well as with the establishment of immunological memory. Although ICD has been characterized with increased precision since its discovery, several questions remain to be addressed. Here, we summarize and tabulate the main molecular, immunological, preclinical, and clinical aspects of ICD, in an attempt to capture the essence of this phenomenon, and identify future challenges for this rapidly expanding field of investigation.

Debris flow magnitudes: a global catalog

The episodic occurrence of debris flow events in response to stochastic precipitation and wildfire events makes hazard prediction challenging. Previous work has shown that frequency-magnitude distributions of non-fire-related debris flows follow a power law, but less is known about the distribution of post-fire debris flows. As a first step in parameterizing hazard models, we use frequency-magnitude distributions and cumulative distribution functions to compare volumes of post-fire debris flows to non-fire-related debris flows. Due to the large number of events required to parameterize frequency-magnitude distributions, and the relatively small number of post-fire event magnitudes recorded in the literature, we collected data on 73 recent post-fire events in the field. The resulting catalog of 988 debris flow events is presented as an appendix to this article. We found that the empirical cumulative distribution function of post-fire debris flow volumes is composed of smaller events than that of non-fire-related debris flows. In addition, the slope of the frequency-magnitude distribution of post-fire debris flows is steeper than that of non-fire-related debris flows, evidence that differences in the post-fire environment tend to produce a higher proportion of small events. We propose two possible explanations: 1) post-fire events occur on shorter return intervals than debris flows in similar basins that do not experience fire, causing their distribution to shift toward smaller events due to limitations in sediment supply, or 2) fire causes changes in resisting and driving forces on a package of sediment, such that a smaller perturbation of the system is required in order for a debris flow to occur, resulting in smaller event volumes.