Whole-body vibration ameliorates glial pathological changes in the hippocampus of hAPP transgenic mice, but does not affect plaque load

BACKGROUND: Alzheimer's disease (AD) is the core cause of dementia in elderly populations. One of the main hallmarks of AD is extracellular amyloid beta (Aβ) accumulation (APP-pathology) associated with glial-mediated neuroinflammation. Whole-Body Vibration (WBV) is a passive form of exercise, but its effects on AD pathology are still unknown.METHODS: Five months old male J20 mice (n = 26) and their wild type (WT) littermates (n = 24) were used to investigate the effect of WBV on amyloid pathology and the healthy brain. Both J20 and WT mice underwent WBV on a vibration platform or pseudo vibration treatment. The vibration intervention consisted of 2 WBV sessions of 10 min per day, five days per week for five consecutive weeks. After five weeks of WBV, the balance beam test was used to assess motor performance. Brain tissue was collected to quantify Aβ deposition and immunomarkers of astrocytes and microglia.RESULTS: J20 mice have a limited number of plaques at this relatively young age. Amyloid plaque load was not affected by WBV. Microglia activation based on IBA1-immunostaining was significantly increased in the J20 animals compared to the WT littermates, whereas CD68 expression was not significantly altered. WBV treatment was effective to ameliorate microglia activation based on morphology in both J20 and WT animals in the Dentate Gyrus, but not so in the other subregions. Furthermore, GFAP expression based on coverage was reduced in J20 pseudo-treated mice compared to the WT littermates and it was significantly reserved in the J20 WBV vs. pseudo-treated animals. Further, only for the WT animals a tendency of improved motor performance was observed in the WBV group compared to the pseudo vibration group.CONCLUSION: In accordance with the literature, we detected an early plaque load, reduced GFAP expression and increased microglia activity in J20 mice at the age of ~ 6 months. Our findings indicate that WBV has beneficial effects on the early progression of brain pathology. WBV restored, above all, the morphology of GFAP positive astrocytes to the WT level that could be considered the non-pathological and hence "healthy" level. Next experiments need to be performed to determine whether WBV is also affective in J20 mice of older age or other AD mouse models.</p

The Interaction between AID and CIB1 Is Nonessential for Antibody Gene Diversification by Gene Conversion or Class Switch Recombination

Activation-induced deaminase (AID) initiates somatic hypermutation, gene conversion and class switch recombination by deaminating variable and switch region DNA cytidines to uridines. AID is predominantly cytoplasmic and must enter the nuclear compartment to initiate these distinct antibody gene diversification reactions. Nuclear AID is relatively short-lived, as it is efficiently exported by a CRM1-dependent mechanism and it is susceptible to proteasome-dependent degradation. To help shed light on mechanisms of post-translational regulation, a yeast-based screen was performed to identify AID-interacting proteins. The calcium and integrin binding protein CIB1 was identified by sequencing and the interaction was confirmed by immunoprecipitation experiments. The AID/CIB1 resisted DNase and RNase treatment, and it is therefore unlikely to be mediated by nucleic acid. The requirement for CIB1 in AID-mediated antibody gene diversification reactions was assessed in CIB1-deficient DT40 cells and in knockout mice, but immunoglobulin gene conversion and class switch recombination appeared normal. The DT40 system was also used to show that CIB1 over-expression has no effect on gene conversion and that AID-EGFP subcellular localization is normal. These combined data demonstrate that CIB1 is not required for AID to mediate antibody gene diversification processes. It remains possible that CIB1 has an alternative, a redundant or a subtle non-limiting regulatory role in AID biology

Detection of degenerative change in lateral projection cervical spine x-ray images

Degenerative changes to the cervical spine can be accompanied by neck pain, which can result from narrowing of the intervertebral disc space and growth of osteophytes. In a lateral x-ray image of the cervical spine, degenerative changes are characterized by vertebral bodies that have indistinct boundaries and limited spacing between vertebrae. In this paper, we present a machine learning approach to detect and localize degenerative changes in lateral x-ray images of the cervical spine. Starting from a user-supplied set of points in the center of each vertebral body, we fit a central spline, from which a region of interest is extracted and image features are computed. A Random Forest classifier labels regions as degenerative change or normal. Leave-one-out cross-validation studies performed on a dataset of 103 patients demonstrates performance of above 95% accuracy

Semi-automatic delineation of the spino-laminar junction curve on lateral X-ray radiographs of the cervical spine

Assessment of the cervical spine using X-ray radiography is an important task when providing emergency room care to trauma patients suspected of a cervical spine injury. In routine clinical practice, a physician will inspect the alignment of the cervical spine vertebrae by mentally tracing three alignment curves along the anterior and posterior sides of the cervical vertebral bodies, as well as one along the spinolaminar junction. In this paper, we propose an algorithm to semi-automatically delineate the spinolaminar junction curve, given a single reference point and the corners of each vertebral body. From the reference point, our method extracts a region of interest, and performs template matching using normalized cross-correlation to find matching regions along the spinolaminar junction. Matching points are then fit to a third order spline, producing an interpolating curve. Experimental results demonstrate promising results, on average producing a modified Hausdorff distance of 1.8 mm, validated on a dataset consisting of 29 patients including those with degenerative change, retrolisthesis, and fracture

<i>Teredinibacter waterburyi</i> sp. nov., a marine, cellulolytic endosymbiotic bacterium isolated from the gills of the wood-boring mollusc <i>Bankia setacea</i> (Bivalvia: Teredinidae) and emended description of the genus <i>Teredinibacter</i>

A cellulolytic, aerobic, gammaproteobacterium, designated strain Bs02T, was isolated from the gills of a marine wood-boring mollusc, Bankia setacea (Bivalvia: Teredinidae). The cells are Gram-stain-negative, slightly curved motile rods (2-5×0.4-0.6 µm) that bear a single polar flagellum and are capable of heterotrophic growth in a simple mineral medium supplemented with cellulose as a sole source of carbon and energy. Cellulose, carboxymethylcellulose, xylan, cellobiose and a variety of sugars also support growth. Strain Bs02T requires combined nitrogen for growth. Temperature, pH and salinity optima (range) for growth were 20 °C (range, 10-30 °C), 8.0 (pH 6.5-8.5) and 0.5 M NaCl (range, 0.0-0.8 M), respectively when grown on 0.5 % (w/v) galactose. Strain Bs02T does not require magnesium and calcium ion concentrations reflecting the proportions found in seawater. The genome size is approximately 4.03 Mbp and the DNA G+C content of the genome is 47.8 mol%. Phylogenetic analyses based on 16S rRNA gene sequences, and on conserved protein-coding sequences, show that strain Bs02T forms a well-supported clade with Teredinibacter turnerae. Average nucleotide identity and percentage of conserved proteins differentiate strain Bs02T from Teredinibacter turnerae at threshold values exceeding those proposed to distinguish bacterial species but not genera. These results indicate that strain Bs02T represents a novel species in the previously monotypic genus Teredinibacter for which the name Teredinibacter waterburyi sp. nov. is proposed. The strain has been deposited under accession numbers ATCC TSD-120T and KCTC 62963T

Benefits for African American and white low-income 7–10-year-old children and their parents taught together in a community-based weight management program in the rural southeastern United States

Abstract Background Low-income children and parents are at increased risk for developing overweight and obesity. Therefore, the purpose of this exploratory study was to compare whether African American and white children and parents benefitted equally from a community-based weight management intervention delivered in two rural counties in southeastern North Carolina (N.C.). Methods We compared the efficacy of the Family Partners for Health intervention for African American and white children and their parents by testing the three-way interaction of the intervention group according to visit and race. Results African American children in the intervention group weighed significantly (P = 0.027) less than those in the control group, while white children in the intervention group weighed less than those in the control group, but the difference did not reach statistical significance. African American and white parents in the intervention group weighed less than their respective control groups across all three data collections, but the difference was only significant in the group of white parents (P = 0.010) at the completion of the study. At the completion of the study, African American children in the intervention group received significantly (P = 0.003) more support for physical activity than African American children in the control group. At both time points, white children in the intervention group were not significantly different from those in the control group. African American parents in the intervention group scored slightly worse in the stress management assessment compared to those in the control group, while white parents in the intervention group showed a significantly (P = 0.041) better level of stress management than those in the control group. At the completion of the study, African American parents in the intervention group scored somewhat worse in emotional eating self-efficacy compared to the scores of the African American parents in the control group, while white parents in the intervention group scored significantly (P < 0.001) better than those in the control group. Conclusions We were successful in affecting some outcomes in both African American and white children and parents using the same intervention. Trial registration NCT01378806 Registered June 22, 2011

Pressure dissociation of integration host factor–DNA complexes reveals flexibility-dependent structural variation at the protein–DNA interface

E. coli Integration host factor (IHF) condenses the bacterial nucleoid by wrapping DNA. Previously, we showed that DNA flexibility compensates for structural characteristics of the four consensus recognition elements associated with specific binding (Aeling et al., J. Biol. Chem. 281, 39236–39248, 2006). If elements are missing, high-affinity binding occurs only if DNA deformation energy is low. In contrast, if all elements are present, net binding energy is unaffected by deformation energy. We tested two hypotheses for this observation: in complexes containing all elements, (1) stiff DNA sequences are less bent upon binding IHF than flexible ones; or (2) DNA sequences with differing flexibility have interactions with IHF that compensate for unfavorable deformation energy. Time-resolved Förster resonance energy transfer (FRET) shows that global topologies are indistinguishable for three complexes with oligonucleotides of different flexibility. However, pressure perturbation shows that the volume change upon binding is smaller with increasing flexibility. We interpret these results in the context of Record and coworker's model for IHF binding (J. Mol. Biol. 310, 379–401, 2001). We propose that the volume changes reflect differences in hydration that arise from structural variation at IHF–DNA interfaces while the resulting energetic compensation maintains the same net binding energy

Incomplete Punishment Networks in Public Goods Games: Experimental Evidence

Abundant evidence suggests that high levels of contributions to public goods can be sustained through self-governed monitoring and sanctioning. This experimental study investigates the effectiveness of decentralized sanctioning institutions in alternative punishment networks. Our results show that the structure of punishment network significantly affects allocations to the public good. In addition, we observe that network configurations are more important than punishment capacities for the levels of public good provision, imposed sanctions and economic efficiency. Lastly, we show that targeted revenge is a major driver of anti-social punishment