Inducing Mild Traumatic Brain Injury in C. elegans via Cavitation-Free Surface Acoustic Wave-Driven Ultrasonic Irradiation.

Mild traumatic brain injury is an all-too-common outcome from modern warfare and sport, and lacks a reproducible model for assessment of potential treatments and protection against it. Here we consider the use of surface acoustic wave (SAW) irradiation of C. elegans worms-without cavitation-as a potential, ethically reasonable animal-on-a-chip model for inducing traumatic brain injury in an animal, producing significant effects on memory and learning that could prove useful in a model that progress from youth to old age in but a few weeks. We show a significant effect by SAW on the ability of worms to learn post-exposure through associative learning chemotaxis. At higher SAW intensity, we find immediate, thorough, but temporary paralysis of the worms. We further explore the importance of homogeneous exposure of the worms to the SAW-driven ultrasound, an aspect poorly controlled in past efforts, if at all, and demonstrate the absence of cavitation through a change in fluids from a standard media for the worms to the exceedingly viscous polyvinyl alcohol. Likewise, we demonstrate that acoustic streaming, when present, is not directly responsible for paralysis nor learning disabilities induced in the worm, but is beneficial at low amplitudes to ensuring homogeneous ultrasound exposure

Loss of Immunohistochemical Reactivity in Association With Handling-Induced Dark Neurons in Mouse Brains.

The handling-induced dark neuron is a histological artifact observed in brain samples handled before fixation with aldehydes. To explore associations between dark neurons and immunohistochemical alterations in mouse brains, we examined protein products encoded by Cav3 (neuronal perikarya/neurites), Rbbp4 (neuronal nuclei), Gfap (astroglia), and Aif1 (microglia) genes in adjacent tissue sections. Here, dark neurons were incidental findings from our prior project, studying the effects of age and high-fat diet on metabolic homeostasis in male C57BL/6N mice. Available were brains from 4 study groups: middle-aged/control diet, middle-aged/high-fat diet, old/control diet, and old/high-fat diet. Young/control diet mice were used as baseline. The hemibrains were immersion-fixed with paraformaldehyde and paraffin-embedded. In the hippocampal formation, we found negative correlations between dark neuron hyperbasophilia and immunoreactivity for CAV3, RBBP4, and glial fibrillary acidic protein (GFAP) using quantitative image analysis. There was no significant difference in dark neuron hyperbasophilia or immunoreactivity for any protein examined among all groups. In contrast, in the hippocampal fimbria, old age seemed to be associated with higher immunoreactivity for GFAP and allograft inflammatory factor-1. Our findings suggest that loss of immunohistochemical reactivity for CAV3, RBBP4, and GFAP in the hippocampal formation is an artifact associated with the occurrence of dark neurons. The unawareness of dark neurons may lead to misinterpretation of immunohistochemical reactivity alterations

Aortic pathology from protein kinase G activation is prevented by an antioxidant vitamin B12 analog.

People heterozygous for an activating mutation in protein kinase G1 (PRKG1, p.Arg177Gln) develop thoracic aortic aneurysms and dissections (TAAD) as young adults. Here we report that mice heterozygous for the mutation have a three-fold increase in basal protein kinase G (PKG) activity, and develop age-dependent aortic dilation. Prkg1R177Q/+ aortas show increased smooth muscle cell apoptosis, elastin fiber breaks, and oxidative stress compared to aortas from wild type littermates. Transverse aortic constriction (TAC)-to increase wall stress in the ascending aorta-induces severe aortic pathology and mortality from aortic rupture in young mutant mice. The free radical-neutralizing vitamin B12-analog cobinamide completely prevents age-related aortic wall degeneration, and the unrelated anti-oxidant N-acetylcysteine ameliorates TAC-induced pathology. Thus, increased basal PKG activity induces oxidative stress in the aorta, raising concern about the widespread clinical use of PKG-activating drugs. Cobinamide could be a treatment for aortic aneurysms where oxidative stress contributes to the disease, including Marfan syndrome

Bone fragility and decline in stem cells in prematurely aging DNA repair deficient trichothiodystrophy mice

Trichothiodystrophy (TTD) is a rare, autosomal recessive nucleotide excision repair (NER) disorder caused by mutations in components of the dual functional NER/basal transcription factor TFIIH. TTD mice, carrying a patient-based point mutation in the Xpd gene, strikingly resemble many features of the human syndrome and exhibit signs of premature aging. To examine to which extent TTD mice resemble the normal process of aging, we thoroughly investigated the bone phenotype. Here, we show that female TTD mice exhibit accelerated bone aging from 39 weeks onwards as well as lack of periosteal apposition leading to reduced bone strength. Before 39 weeks have passed, bones of wild-type and TTD mice are identical excluding a developmental defect. Albeit that bone formation is decreased, osteoblasts in TTD mice retain bone-forming capacity as in vivo PTH treatment leads to increased cortical thickness. In vitro bone marrow cell cultures showed that TTD osteoprogenitors retain the capacity to differentiate into osteoblasts. However, after 13 weeks of age TTD females show decreased bone nodule formation. No increase in bone resorption or the number of osteoclasts was detected. In conclusion, TTD mice show premature bone aging, which is preceded by a decrease in mesenchymal stem cells/osteoprogenitors and a change in systemic factors, identifying DNA damage and repair as key determinants for bone fragility by influencing osteogenesis and bone metabolism

Low Temperature Expansions for Potts Models

On simple cubic lattices, we compute low temperature series expansions for the energy, magnetization and susceptibility of the three-state Potts model in D=2 and D=3 to 45 and 39 excited bonds respectively, and the eight-state Potts model in D=2 to 25 excited bonds. We use a recursive procedure which enumerates states explicitly. We analyze the series using Dlog Pade analysis and inhomogeneous differential approximants.Comment: (17 pages + 8 figures

The Role of Phonological Awareness and Phonetic Radical Awareness in Acquiring Chinese Literacy Skills in Learners of Chinese as a Second Language

There is much research into the roles of phonological awareness and phonetic radical awareness in the development of Chinese character reading and writing skills in native-speaking children, but there is comparatively little work on the relationship between such metalinguistic skills and character literacy skills in adult learners of Chinese a second language (CSL). In this study, we explored this issue with 83 Arabic and English CSL learners who had studied Chinese in their home country. Their knowledge of phonological awareness, phonetic radical awareness, and Chinese character reading and writing was measured. There were two main findings. Firstly, the learners’ phonological awareness, but not their phonetic radical awareness, predicted the acquisition of character reading and writing skills directly or indirectly. Secondly, phonetic radical awareness did not mediate the effect of phonological awareness on character reading and writing skills. The results point to the different roles that phonological awareness and phonetic radical awareness play in the development of character literacy skills, and the still unclear relationship between phonological awareness and phonetic radical awareness. These findings are important for understanding the contribution of phonological awareness and phonetic radical awareness to the acquisition of character literacy skills for CSL learners