Increased Noradrenergic Metabolism in the Cerebellum of the Mouse Mutant Dystonia Musculorum

Abstract: The neurological mouse mutant dystonia musculorum exhibits bizarre appendicular and truncal dystonia without known cerebellar histopathology. We evaluated striatal dopamine and cerebellar norepinephrine metabolism in this mutant and compared the results with those obtained in wild-type BALB/c and B6C3 controls. Tyrosine hydroxylase activity and dopamine metabolite levels (homovanillic acid and 3,4-dihydroxyphenylacetic acid) in the striatum of the mutant were similar to controls. Tyrosine hydroxylase activity and the steady-state level of 3-methoxy-4-hydroxyphenethyleneglycol, a metabolite of norepinephrine, in the cerebellum were 38% and 42-66%, respectively, greater in the mutant. However, the level of norepinephrine was similar (∼350 ng/g). Further, a Purkinje cell-specific marker, cGMP-dependent protein kinase, was unchanged in the mutant and no Purkinje cell pathology was observed with light microscopy. The lack of Purkinje cell derangement and similar levels of cerebellar norepinephrine and cGMP-dependent protein kinase activity suggest that increased norepinephrine metabolism in the cerebellum of this mutant is not a morphological response to gross target cell loss during morphogenesis. The observed changes may be a reaction to abnormal impulse traffic or altered input/output pathways to the mutant cerebellum during its development.     

Analysis of development and growth in a mutant of Physarum polycephalum with defective cytokinesis

Cultures of amoebae of the mutant strain ATS23 isolated from strain CLd of Physarum polycephalum contain multinucleate cells and cells with increased nuclear DNA content. Plasmodia derived from ATS23 clones show abnormal morphology and defective sporulation. All abnormalities are enhanced by high incubation temperature (31 °C). Genetic analysis suggested that all the abnormalities were caused by a single mutation, denoted hts-23. The kinetics of plasmodium formation were followed in cultures of apogamic amoebae carrying hts-23 and hts⁺ (wild type) respectively. Results indicated that, relative to wild type, hts-23 did not increase the rate of plasmodium formation. There was evidence that, in both mutant and wild-type strains, commitment to plasmodium development occurred in uninucleate cells. Analysis of cell pedigrees by time-lapse cinematography indicated that the primary abnormal event in cultures of hts-23 amoebae was failure of cytokinesis; an apparently complete cleavage furrow was formed but cell separation failed, resulting in a binucleate cell. This event occurred randomly in pedigrees in which the majority of divisions were completed normally; its frequency increased during incubation at 31 °C. All other abnormalities in hts-23 amoebal cultures could be attributed to this primary event, assuming that DNA synthesis continued in the absence of cytokinesis and that the binucleate cells underwent the amoebal type of “open” mitosis, allowing the possibility of spindle fusion. This implies that the acquisition of “closed” mitosis is an essential early step in plasmodium development.     

Auditory sensitivity of the saccule in the American toad (Bufo americanus)

Summary Single unit recordings in the posterior nerve branchlet from the saccule have shown that, in the American toad (Bufo americanus), approximately 30% of the fibers respond to airborne sounds in a way similar to fibers from the two known auditory organs, the amphibian and basilar papillae. In response to tones, saccule fibers have best excitatory frequencies which fall into two disjoint populations: units in the low-frequency-sensitive group (below 300 Hz) show tone-on-tone suppression while those in the high-frequency-sensitive group (700–1,200 Hz) show no evidence of peripheral inhibition. Saccule units have somewhat higher thresholds than those from the other auditory organs. It is suggested that the high-frequency-sensitive fibers might be useful for discriminating mating calls in an intense chorus while the low-frequency-sensitive units likely respond to other high intensity sounds in the environment.Research supported by the U.S. Public Health Service (NIH grant NS-09244).     

Étude des variations du nombre et de la répartition des muscles longitudinaux chez Phoronis psammophila Cori

In 21 samples, staggered over 18 months, 1725 composite muscle formulae have been established for Phoronis psammophila Cori. The study of variations of the number and distribution of longitudinal muscle bundles demonstrates the increase of the muscle number (3 or 4) with the age of the animals. This increase is displayed with difficulty because of the interactions of many phenomena, especially reproduction and so statistical tests have not indicated significance. The general and especially mean formulae of different samples do not indicate the increase of the number of muscle bundles with time, as proposed by Emig.     

CBEA: Competitive balances for taxonomic enrichment analysis

Research in human-associated microbiomes often involves the analysis of taxonomic count tables generated via high-throughput sequencing. It is difficult to apply statistical tools as the data is high-dimensional, sparse, and compositional. An approachable way to alleviate high-dimensionality and sparsity is to aggregate variables into pre-defined sets. Set-based analysis is ubiquitous in the genomics literature and has demonstrable impact on improving interpretability and power of downstream analysis. Unfortunately, there is a lack of sophisticated set-based analysis methods specific to microbiome taxonomic data, where current practice often employs abundance summation as a technique for aggregation. This approach prevents comparison across sets of different sizes, does not preserve inter-sample distances, and amplifies protocol bias. Here, we attempt to fill this gap with a new single-sample taxon enrichment method that uses a novel log-ratio formulation based on the competitive null hypothesis commonly used in the enrichment analysis literature. Our approach, titled competitive balances for taxonomic enrichment analysis (CBEA), generates sample-specific enrichment scores as the scaled log-ratio of the subcomposition defined by taxa within a set and the subcomposition defined by its complement. We provide sample-level significance testing by estimating an empirical null distribution of our test statistic with valid p-values. Herein, we demonstrate, using both real data applications and simulations, that CBEA controls for type I error, even under high sparsity and high inter-taxa correlation scenarios. Additionally, CBEA provides informative scores that can be inputs to downstream analyses such as prediction tasks.     

Enzyme activation for organic solvents made easy

Enzymes are highly selective catalysts that perform intricate chemistries at ambient temperatures and pressures. Although water is the solvent of life, it is a poor solvent for most synthetic organic reactions and, therefore, most chemists avoid aqueous solutions for synthetic applications. However, when removed from the aqueous environment and placed in an organic solvent, enzyme activity is reduced greatly. Here, we present a general overview of recent efforts to activate enzymes for use in nonaqueous media, giving particular focus to the use of simple salts as additives that result in significant biocatalytic improvements.     

Syndecan-4 associates with alpha-actinin

Cell adhesion to the extracellular matrix influences many cellular functions. The integrin family of matrix receptors plays major roles in the formation of adhesions, but other proteins modulate integrin signaling. Syndecan-4, a transmembrane proteoglycan, cooperatively signals with integrins during the formation of focal adhesions. To date, a direct link between syndecan-4 and the cytoskeleton has remained elusive. We now demonstrate by Triton X-100 extraction immunoprecipitation and in vitro binding assays that the focal adhesion component alpha-actinin interacts with syndecan-4 in a beta-integrin-independent manner.