Malignant Glioma Arising at the Site of an Excised Cerebellar Hemangioblastoma after Irradiation in a von Hippel-Lindau Disease Patient

We describe herein a malignant glioma arising at the site of the resected hemangioblastoma after irradiation in a patient with von Hippel-Lindau disease (VHL). The patient was a 25 year-old male with multiple hemangioblastomas at the cerebellum and spinal cord, multiple pancreatic cysts and a renal cell carcinoma; he was diagnosed as having VHL disease. The largest hemangioblastoma at the right cerebellar hemisphere was completely removed, and he received high-dose irradiation postoperatively. The tumor recurred at the same site 7 years later, which was a malignant glioma with no evidence of hemangioblastoma. The malignant glioma showed molecular genetic profiles of radiation-induced tumors because of its diffuse p53 immunostaining and the loss of p16 immunoreactivity. The genetic study to find the loss of heterozygosity (LOH) of VHL gene revealed that only the cerebellar hemangioblastoma showed allelic losses for the gene. To the best of our knowledge, this report is the first to show a malignant glioma that developed in a patient with VHL disease after radiation therapy at the site of an excised hemangioblastoma. This report also suggests that radiation therapy should be performed very carefully in VHL patients with hemangioblastomas

Growth Kinetics in Layer‐by‐Layer Assemblies of Organic Nanoparticles and Polyelectrolytes

The growth rates of layer‐by‐layer (LbL) assemblies of polyelectrolytes (PEs) with oppositely charged polystyrene (PS) nanoparticles (NPs) as a function of molecular weight (MW) of the PEs, ionic strength of the media, and NP size and charge are systematically investigated. To optimize LbL growth, the effects of suspension concentration, pH of the media, and deposition time on the growth rate of multilayers are assessed. Both linear and exponential growth behaviors are observed and, under optimal conditions, films of up to around 1 μm thick can readily be assembled after 10 or so bilayers have been deposited. For many of the cases studied, an intermediate MW of PE leads to the fastest film buildup, for both cationic poly(ethyleneimine) deposited alternately with anionic PS NPs and for anionic poly(acrylic acid) deposited alternately with cationic PS NPs. The existence of an optimal MW suggests that growth rate is determined by a balance of thermodynamic factors, including density of polymer bridges between particles, and kinetic factors, specifically the diffusivity of polymer in the film. The optimal MW, however, is very sensitive to the materials used. Moreover, depending on the MW of the PE, increasing salinity could increase or decrease the growth kinetics. Finally, the surface morphology of the films is characterized with AFM and SEM to reveal that the roughness increases less than linearly with film thickness.Growth factors: The growth rates of layer‐by‐layer (LbL) assemblies of polyelectrolytes (PEs) with oppositely charged polystyrene nanoparticles are systematically investigated. The molecular weight of a PE has a considerable effect on LbL film growth and its surface morphology (see figure).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135666/1/cphc201600789_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135666/2/cphc201600789-sup-0001-misc_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135666/3/cphc201600789.pd

Studying strategies and types of players:Experiments, logics and cognitive models

How do people reason about their opponent in turn-taking games? Often, people do not make the decisions that game theory would prescribe. We present a logic that can play a key role in understanding how people make their decisions, by delineating all plausible reasoning strategies in a systematic manner. This in turn makes it possible to construct a corresponding set of computational models in a cognitive architecture. These models can be run and fitted to the participants’ data in terms of decisions, response times, and answers to questions. We validate these claims on the basis of an earlier game-theoretic experiment about the turn-taking game “Marble Drop with Surprising Opponent”, in which the opponent often starts with a seemingly irrational move. We explore two ways of segregating the participants into reasonable “player types”. The first way is based on latent class analysis, which divides the players into three classes according to their first decisions in the game: Random players, Learners, and Expected players, who make decisions consistent with forward induction. The second way is based on participants’ answers to a question about their opponent, classified according to levels of theory of mind: zero-order, first-order and second-order. It turns out that increasing levels of decisions and theory of mind both correspond to increasing success as measured by monetary awards and increasing decision times. Next, we use the logical language to express different kinds of strategies that people apply when reasoning about their opponent and making decisions in turn-taking games, as well as the ‘reasoning types’ reflected in their behavior. Then, we translate the logical formulas into computational cognitive models in the PRIMs architecture. Finally, we run two of the resulting models, corresponding to the strategy of only being interested in one’s own payoff and to the myopic strategy, in which one can only look ahead to a limited number of nodes. It turns out that the participant data fit to the own-payoff strategy, not the myopic one. The article closes the circle from experiments via logic and cognitive modelling back to predictions about new experiments

Phylogenomics of Reichenowia parasitica, an Alphaproteobacterial Endosymbiont of the Freshwater Leech Placobdella parasitica

Although several commensal alphaproteobacteria form close relationships with plant hosts where they aid in (e.g.,) nitrogen fixation and nodulation, only a few inhabit animal hosts. Among these, Reichenowia picta, R. ornata and R. parasitica, are currently the only known mutualistic, alphaproteobacterial endosymbionts to inhabit leeches. These bacteria are harbored in the epithelial cells of the mycetomal structures of their freshwater leech hosts, Placobdella spp., and these structures have no other obvious function than housing bacterial symbionts. However, the function of the bacterial symbionts has remained unclear. Here, we focused both on exploring the genomic makeup of R. parasitica and on performing a robust phylogenetic analysis, based on more data than previous hypotheses, to test its position among related bacteria. We sequenced a combined pool of host and symbiont DNA from 36 pairs of mycetomes and performed an in silico separation of the different DNA pools through subtractive scaffolding. The bacterial contigs were compared to 50 annotated bacterial genomes and the genome of the freshwater leech Helobdella robusta using a BLASTn protocol. Further, amino acid sequences inferred from the contigs were used as queries against the 50 bacterial genomes to establish orthology. A total of 358 orthologous genes were used for the phylogenetic analyses. In part, results suggest that R. parasitica possesses genes coding for proteins related to nitrogen fixation, iron/vitamin B translocation and plasmid survival. Our results also indicate that R. parasitica interacts with its host in part by transmembrane signaling and that several of its genes show orthology across Rhizobiaceae. The phylogenetic analyses support the nesting of R. parasitica within the Rhizobiaceae, as sister to a group containing Agrobacterium and Rhizobium species

Metabolism of multiple glycosaminoglycans by <i>Bacteroides thetaiotaomicron</i> is orchestrated by a versatile core genetic locus

The human gut microbiota (HGM), which is critical to human health, utilises complex glycans as its major carbon source. Glycosaminoglycans represent an important, high priority, nutrient source for the HGM. Pathways for the metabolism of various glycosaminoglycan substrates remain ill-defined. Here we perform a biochemical, genetic and structural dissection of the genetic loci that orchestrates glycosaminoglycan metabolism in the organism Bacteroides thetaiotaomicron. Here, we report: the discovery of two previously unknown surface glycan binding proteins which facilitate glycosaminoglycan import into the periplasm; distinct kinetic and genetic specificities of various periplasmic lyases which dictate glycosaminoglycan metabolic pathways; understanding of endo sulfatase activity questioning the paradigm of how the ‘sulfation problem’ is handled by the HGM; and 3D crystal structures of the polysaccharide utilisation loci encoded sulfatases. Together with comparative genomic studies, our study fills major gaps in our knowledge of glycosaminoglycan metabolism by the HGM

Unanesthetized Auditory Cortex Exhibits Multiple Codes for Gaps in Cochlear Implant Pulse Trains

Cochlear implant listeners receive auditory stimulation through amplitude-modulated electric pulse trains. Auditory nerve studies in animals demonstrate qualitatively different patterns of firing elicited by low versus high pulse rates, suggesting that stimulus pulse rate might influence the transmission of temporal information through the auditory pathway. We tested in awake guinea pigs the temporal acuity of auditory cortical neurons for gaps in cochlear implant pulse trains. Consistent with results using anesthetized conditions, temporal acuity improved with increasing pulse rates. Unlike the anesthetized condition, however, cortical neurons responded in the awake state to multiple distinct features of the gap-containing pulse trains, with the dominant features varying with stimulus pulse rate. Responses to the onset of the trailing pulse train (Trail-ON) provided the most sensitive gap detection at 1,017 and 4,069 pulse-per-second (pps) rates, particularly for short (25 ms) leading pulse trains. In contrast, under conditions of 254 pps rate and long (200 ms) leading pulse trains, a sizeable fraction of units demonstrated greater temporal acuity in the form of robust responses to the offsets of the leading pulse train (Lead-OFF). Finally, TONIC responses exhibited decrements in firing rate during gaps, but were rarely the most sensitive feature. Unlike results from anesthetized conditions, temporal acuity of the most sensitive units was nearly as sharp for brief as for long leading bursts. The differences in stimulus coding across pulse rates likely originate from pulse rate-dependent variations in adaptation in the auditory nerve. Two marked differences from responses to acoustic stimulation were: first, Trail-ON responses to 4,069 pps trains encoded substantially shorter gaps than have been observed with acoustic stimuli; and second, the Lead-OFF gap coding seen for <15 ms gaps in 254 pps stimuli is not seen in responses to sounds. The current results may help to explain why moderate pulse rates around 1,000 pps are favored by many cochlear implant listeners

Large-Scale Assessment of the Zebrafish Embryo as a Possible Predictive Model in Toxicity Testing

Background: In the drug discovery pipeline, safety pharmacology is a major issue. The zebrafish has been proposed as a model that can bridge the gap in this field between cell assays (which are cost-effective, but low in data content) and rodent assays (which are high in data content, but less cost-efficient). However, zebrafish assays are only likely to be useful if they can be shown to have high predictive power. We examined this issue by assaying 60 water-soluble compounds representing a range of chemical classes and toxicological mechanisms. Methodology/Principal Findings: Over 20,000 wild-type zebrafish embryos (including controls) were cultured individually in defined buffer in 96-well plates. Embryos were exposed for a 96 hour period starting at 24 hours post fertilization. A logarithmic concentration series was used for range-finding, followed by a narrower geometric series for LC 50 determination. Zebrafish embryo LC50 (log mmol/L), and published data on rodent LD50 (log mmol/kg), were found to be strongly correlated (using Kendall’s rank correlation tau and Pearson’s product-moment correlation). The slope of the regression line for the full set of compounds was 0.73403. However, we found that the slope was strongly influenced by compound class. Thus, while most compounds had a similar toxicity level in both species, some compounds were markedly more toxic in zebrafish than in rodents, or vice versa. Conclusions: For the substances examined here, in aggregate, the zebrafish embryo model has good predictivity for toxicit