Bioeffects Considerations for Diagnostic Ultrasound Contrast Agents

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135236/1/jum2008274611.pd

Presynaptic partner selection during retinal circuit reassembly varies with timing of neuronal regeneration in vivo

Whether neurons can restore their original connectivity patterns during circuit repair is unclear. Taking advantage of the regenerative capacity of zebrafish retina, we show here the remarkable specificity by which surviving neurons reassemble their connectivity upon regeneration of their major input. H3 horizontal cells (HCs) normally avoid red and green cones, and prefer ultraviolet over blue cones. Upon ablation of the major (ultraviolet) input, H3 HCs do not immediately increase connectivity with other cone types. Instead, H3 dendrites retract and re-extend to contact new ultraviolet cones. But, if regeneration is delayed or absent, blue-cone synaptogenesis increases and ectopic synapses are made with red and green cones. Thus, cues directing synapse specificity can be maintained following input loss, but only within a limited time period. Further, we postulate that signals from the major input that shape the H3 HC's wiring pattern during development persist to restrict miswiring after damage

Fitness Ranking of Individual Mutants Drives Patterns of Epistatic Interactions in HIV-1

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

An experimental investigation into the dimensional error of powder-binder three-dimensional printing

This paper is an experimental investigation into the dimensional error of the rapid prototyping additive process of powder-binder three-dimensional printing. Ten replicates of a purpose-designed part were produced using a three-dimensional printer, and measurements of the internal and external features of all surfaces were made using a general purpose coordinate measuring machine. The results reveal that the bases of all replicates (nominally flat) have a concave curvature, producing a flatness error of the primary datum. This is in contrast to findings regarding other three-dimensional printing processes, widely reported in the literature, where a convex curvature was observed. All external surfaces investigated in this study showed positive deviation from nominal values, especially in the z-axis. The z-axis error consisted of a consistent positive cumulative error and a different constant error in different replicates. By compensating for datum surface error, the average total height error of the test parts can be reduced by 25.52 %. All the dimensional errors are hypothesised to be explained by expansion and the subsequent distortion caused by layer interaction during and after the printing process

Genetic signs of multiple colonization events in Baltic ciscoes with radiation into sympatric spring- and autumn-spawners confined to early postglacial arrival

Presence of sympatric populations may reflect local diversification or secondary contact of already distinct forms. The Baltic cisco (Coregonus albula) normally spawns in late autumn, but in a few lakes in Northern Europe sympatric autumn and spring- or winter-spawners have been described. So far, the evolutionary relationships and taxonomic status of these main life history forms have remained largely unclear. With microsatellites and mtDNA sequences, we analyzed extant and extinct spring- and autumn-spawners from a total of 23 Swedish localities, including sympatric populations. Published sequences from Baltic ciscoes in Germany and Finland, and Coregonus sardinella from North America were also included together with novel mtDNA sequences from Siberian C.sardinella. A clear genetic structure within Sweden was found that included two population assemblages markedly differentiated at microsatellites and apparently fixed for mtDNA haplotypes from two distinct clades. All sympatric Swedish populations belonged to the same assemblage, suggesting parallel evolution of spring-spawning rather than secondary contact. The pattern observed further suggests that postglacial immigration to Northern Europe occurred from at least two different refugia. Previous results showing that mtDNA in Baltic cisco is paraphyletic with respect to North American C.sardinella were confirmed. However, the inclusion of Siberian C.sardinella revealed a more complicated pattern, as these novel haplotypes were found within one of the two main C.albula clades and were clearly distinct from those in North American C.sardinella. The evolutionary history of Northern Hemisphere ciscoes thus seems to be more complex than previously recognized

Redirected nuclear glutamate dehydrogenase supplies Tet3 with alpha-ketoglutarate in neurons

Tet3 is the main alpha -ketoglutarate (alpha KG)-dependent dioxygenase in neurons that converts 5-methyl-dC into 5-hydroxymethyl-dC and further on to 5-formyl- and 5-carboxy-dC. Neurons possess high levels of 5-hydroxymethyl-dC that further increase during neural activity to establish transcriptional plasticity required for learning and memory functions. How alpha KG, which is mainly generated in mitochondria as an intermediate of the tricarboxylic acid cycle, is made available in the nucleus has remained an unresolved question in the connection between metabolism and epigenetics. We show that in neurons the mitochondrial enzyme glutamate dehydrogenase, which converts glutamate into alpha KG in an NAD(+)-dependent manner, is redirected to the nucleus by the alpha KG-consumer protein Tet3, suggesting on-site production of alpha KG. Further, glutamate dehydrogenase has a stimulatory effect on Tet3 demethylation activity in neurons, and neuronal activation increases the levels of alpha KG. Overall, the glutamate dehydrogenase-Tet3 interaction might have a role in epigenetic changes during neural plasticity. alpha -ketoglutarate (alpha KG) is an intermediate in the tricarboxylic acid cycle that is required in the nucleus for genomic DNA demethylation by Tet3. Here, the authors show that the enzyme glutamate dehydrogenase, which converts glutamate to alpha KG, is redirected from the mitochondria to the nucleus.Proteomic

Behavioural evidence for self-medication in bumblebees?

The presence of antimicrobial secondary metabolites in nectar suggests that pollinators, which are threatened globally by emergent disease, may benefit from the consumption of nectars rich in these metabolites. We tested whether nicotine, a nectar secondary metabolite common in Solanaceae and Tilia species, is used by parasitized bumblebees as a source of self-medication , using a series of toxicological, microbiological and behavioural experiments. Caged bees infected with Crithidia bombi had a slight preference for sucrose solution laced with the alkaloid and behavioural tests showed that the parasite infection induced an increased consumption of nicotine during foraging activity, though nicotine had an appetite-reducing effect overall. When ingested, nicotine delayed the progression of a gut infection in bumblebees by a few days, but dietary nicotine did not clear the infection, and after 10 days the parasite load approached that of control bees. Moreover, when pathogens were exposed to the alkaloid prior to host ingestion, the protozoan's viability was not directly affected, suggesting that anti-parasite effects were relatively weak. Nicotine consumption in a single dose did not impose any cost even in starved bees but the alkaloid had detrimental effects on healthy bees if consistently consumed for weeks. These toxic effects disappeared in infected bees, suggesting that detoxification costs might have been counterbalanced by the advantages in slowing the progression of the infection. Nicotine consumption did not affect bee lifespan but the reduction in the parasite load may have other likely unexplored subtle benefits both for individual bees and their colony.  Potential evidence for self-medication is discussed. The contention that secondary metabolites in nectar may be under selection from pollinators, or used by plants to enhance their own reproductive success, remains to be confirmed.D.B. was supported by a Marie Curie Intra European Fellowship within the 7th European Community Framework Programm

Leptin and Adiponectin: new players in the field of tumor cell and leukocyte migration

Adipose tissue is no longer considered to be solely an energy storage, but exerts important endocrine functions, which are primarily mediated by a network of various soluble factors derived from fat cells, called adipocytokines. In addition to their responsibility to influence energy homeostasis, new studies have identified important pathways linking metabolism with the immune system, and demonstrating a modulatory role of adipocytokines in immune function. Additionally, epidemiological studies underline that obesity represents a significant risk factor for the development of cancer, although the exact mechanism of this relationship remains to be determined. Whereas a possible influence of adipocytokines on the proliferation of tumor cells is already known, new evidence has come to light elucidating a modulatory role of this signaling substances in the regulation of migration of leukocytes and tumor cells. The migration of leukocytes is a key feature to fight cancer cells, whereas the locomotion of tumor cells is a prerequisite for tumor formation and metastasis. We herein review the latest tumor biological findings on the role of the most prominent adipocytokines leptin and adiponectin, which are secreted by fat cells, and which are involved in leukocyte migration, tumor growth, invasion and metastasis. This review thus accentuates the complex, interactive involvement of adipocytokines in the regulation of migration of both leukocytes and tumor cells, and gives an insight in the underlying molecular mechanisms