PPAR-γ Thiazolidinedione Agonists and Immunotherapy in the Treatment of Brain Tumors

Thiazolidinediones (TZDs) are selective agonists of the peroxisome proliferator-activated receptor (PPAR) gamma, a transcription factor belonging to the superfamily of nuclear hormone receptors. Although activation of PPARγ by TZDs has been best characterized by its ability to regulate expression of genes associated with lipid metabolism, PPARγ agonists have other physiological effects including modulating pro- and anti-inflammatory gene expression and inducing apoptosis in several cell types including glioma cells and cell lines. Immunotherapeutic approaches to reducing brain tumors are focused on means to reduce the immunosuppressive responses of tumors which dampen the ability of cytotoxic T-lymphocytes to kill tumors. Initial studies from our lab show that combination of an immunotherapeutic strategy with TZD treatment provides synergistic benefit in animals with implanted tumors. The potential of this combined approach for treatment of brain tumors is reviewed in this report

Evidence for the involvement of more than one mRNA species in controlling the inactivation process of rat and rabbit brain Na channels expressed in Xenopus oocytes

The properties of rat and rabbit brain sodium (Na) channels expressed in Xenopus oocytes following either unfractionated or high-molecular- weight mRNA injections were compared to assess the relative contribution of different size messages to channel function. RNA was size-fractionated on a sucrose gradient and a high-molecular-weight fraction (7–10 kilobase) encoding the α-subunit gave rise to functional voltage-dependent Na channels in the oocyte membrane. Single- channel conductance, mean open time, and time to first opening were all similar to the values for channels following injection of unfractionated RNA. In contrast, inactivation properties were markedly different; Na currents from high-molecular-weight RNA inactivated with a several-fold smaller macroscopic inactivation rate and showed a steady-state voltage dependence that was shifted in the depolarizing direction by at least 10 mV relative to that for unfractionated RNA. Single-channel recording revealed that the kinetic difference arose from a greater probability for high-molecular-weight RNA induced channels to reopen during a depolarizing voltage step. Pooling all gradient fractions and injecting this RNA into oocytes led to the appearance of Na channels with inactivation properties indistinguishable from those following injection of unfractionated RNA. These results suggest that mRNA species not present in the high- molecular-weight fraction can influence the inactivation process of rat brain Na channels expressed in Xenopus oocytes. This mRNA may encode β-subunits or other proteins that are involved in posttranslational processing of voltage-dependent Na channels

Evidence for the involvement of more than one mRNA species in controlling the inactivation process of rat and rabbit brain Na channels expressed in Xenopus oocytes

The properties of rat and rabbit brain sodium (Na) channels expressed in Xenopus oocytes following either unfractionated or high-molecular- weight mRNA injections were compared to assess the relative contribution of different size messages to channel function. RNA was size-fractionated on a sucrose gradient and a high-molecular-weight fraction (7–10 kilobase) encoding the α-subunit gave rise to functional voltage-dependent Na channels in the oocyte membrane. Single- channel conductance, mean open time, and time to first opening were all similar to the values for channels following injection of unfractionated RNA. In contrast, inactivation properties were markedly different; Na currents from high-molecular-weight RNA inactivated with a several-fold smaller macroscopic inactivation rate and showed a steady-state voltage dependence that was shifted in the depolarizing direction by at least 10 mV relative to that for unfractionated RNA. Single-channel recording revealed that the kinetic difference arose from a greater probability for high-molecular-weight RNA induced channels to reopen during a depolarizing voltage step. Pooling all gradient fractions and injecting this RNA into oocytes led to the appearance of Na channels with inactivation properties indistinguishable from those following injection of unfractionated RNA. These results suggest that mRNA species not present in the high- molecular-weight fraction can influence the inactivation process of rat brain Na channels expressed in Xenopus oocytes. This mRNA may encode β-subunits or other proteins that are involved in posttranslational processing of voltage-dependent Na channels

Low temperature characterization of modulation doped SiGe grown on bonded silicon-on-insulator

Modulation doped pseudomorphic Si0.87Ge0.13 strained quantum wells were grown on bonded silicon-on-insulator (SOI) substrates. Comparison with similar structures grown on bulk Si(100) wafers shows that the SOI material has higher mobility at low temperatures with a maximum value of 16 810 cm 2/V s for 2.05 × 1011 cm – 2 carries at 298 mK. Effective masses obtained from the temperature dependence of Shubnikov–de Haas oscillations have a value of (0.27 ± 0.02) m0 compared to (0.23 ± 0.02) m0 for quantum wells on Si(100) while the cyclotron resonance effective masses obtained at higher magnetic fields without consideration for nonparabolicity effects have values between 0.25 and 0.29 m0. Ratios of the transport and quantum lifetimes, tau/tau q=2.13 ± 0.10, were obtained for the SOI material that are, we believe, the highest reported for any pseudomorphic SiGe modulation doped structure and demonstrates that there is less interface roughness or charge scattering in the SOI material than in metal–oxide–semiconductor field effect transistors or other pseudomorphic SiGe modulation doped quantum wells

Predictors and correlates of perceived cognitive decline in retired professional rugby league players

Objective: Rugby league is an international full-contact sport, with frequent concussive injuries. Participation in other full-contact sports such as American football has been considered to be a risk factor for neuropsychiatric sequelae later-in-life, but little research has addressed the mental and cognitive health of retired professional rugby league players. We examined predictors and correlates of perceived (self-reported) cognitive decline in retired National Rugby League (NRL) players. Methods: Participants were 133 retired male elite level rugby league players in Australia. Participants completed clinical interviews, neuropsychological testing, and self-report measures. The Informant Questionnaire on Cognitive Decline in the Elderly, self-report (IQCODE-Self), measured perceived cognitive decline. Results: The median age of the sample was 55.0 (M = 53.1, SD = 13.9, range = 30–89) and the median years of education completed was 12.0 (M = 11.9, SD = 2.6, range = 7–18). The retired players reported a median of 15.0 total lifetime concussions (M = 28.0, SD = 36.6, range = 0–200). The mean IQCODE-Self score was 3.2 (SD = 0.5; Range = 1.3–5.0); 10/133 (7.5%) and 38/133 (28.6%) scored above conservative and liberal cutoffs for cognitive decline on the IQCODE-Self, respectively. Perceived cognitive decline was positively correlated with current depressive symptoms, negatively correlated with years of professional sport exposure and resilience, and unrelated to objective cognition and number of self-reported concussions. A multiple regression model with perceived cognitive decline regressed on age, concussion history, professional rugby league exposure, depression, resilience, objective cognitive functioning, daytime sleepiness, and pain severity showed depression as the only significant predictor. Conclusion: This is the first large study examining subjectively experienced cognitive decline in retired professional rugby league players. Similar to studies from the general population and specialty clinics, no relationship was found between objective cognitive test performance and perceived cognitive decline. Depressive symptoms emerged as the strongest predictor of perceived cognitive decline, suggesting that subjective reports of worsening cognition in retired elite rugby league players might reflect psychological distress rather than current cognitive impairment

Video analysis and verification of direct head impacts recorded by wearable sensors in junior rugby league players

Background: Rugby league is a high-intensity collision sport that carries a risk of concussion. Youth athletes are considered to be more vulnerable and take longer to recover from concussion than adult athletes. Purpose: To review head impact events in elite-level junior representative rugby league and to verify and describe characteristics of X-patchTM-recorded impacts via video analysis. Study Design: Observational case series. Methods: The X-patchTM was used on twenty-one adolescent players (thirteen forwards and eight backs) during a 2017 junior representative rugby league competition. Game-day footage, recorded by a trained videographer from a single camera, was synchronised with X-patchTM-recorded timestamped events. Impacts were double verified by video review. Impact rates, playing characteristics, and gameplay situations were described. Results: The X-patchTM-recorded 624 impacts ≥ 20g between game start and finish, of which 564 (90.4%) were verified on video. Upon video review, 413 (73.2%) of all verified impacts ≥ 20g where determined to be direct head impacts. Direct head impacts ≥ 20g occurred at a rate of 5.2 impacts per game hour; 7.6 for forwards and 3.0 for backs (range = 0–18.2). A defender’s arm directly impacting the head of the ball carrier was the most common event, accounting for 21.3% (n = 120) of all impacts, and 46.7% of all “hit-up” impacts. There were no medically diagnosed concussions during the competition. Conclusion: The majority (90.4%) of head impacts ≥ 20g recorded by the X-patchTM sensor were verified by video. Double verification of direct head impacts in addition to cross-verification of sensor-recorded impacts using a secondary source such as synchronised video review can be used to ensure accuracy and validation of data

Verifying head impacts recorded by a wearable sensor using video footage in rugby league: A preliminary study

Background: Rugby league is a full-contact collision sport with an inherent risk of concussion. Wearable instrumented technology was used to observe and characterize the level of exposure to head impacts during game play. Purpose: To verify the impacts recorded by the x-patch™ with video analysis. Study design: Observational case series. Methods: The x-patch™ was used on eight men’s semi-professional rugby league players during the 2016 Newcastle Rugby League competition (five forwards and three backs). Game day footage was recorded by a trained videographer using a single camera located at the highest midfield location to verify the impact recorded by the x-patch™. Videographic and accelerometer data were time synchronized. Results: The x-patch™ sensors recorded a total of 779 impacts ≥ 20 g during the games, of which 732 (94.0%) were verified on video. In addition, 817 impacts were identified on video that did not record an impact on the sensors. The number of video-verified impacts ≥ 20 g, per playing hour, was 7.8 for forwards and 4.8 for backs (range = 3.9–19.0). Impacts resulting in a diagnosed concussion had much greater peak linear acceleration (M = 76.1 g, SD = 17.0) than impacts that did not result in a concussion (M = 34.2g, SD = 18.0; Cohen’s d = 2.4). Conclusions: The vast majority (94%) of impacts ≥ 20 g captured by the x-patch™ sensor were video verified in semi-professional rugby league games. The use of a secondary source of information to verify impact events recorded by wearable sensors is beneficial in clarifying game events and exposure levels

Twisted brane charges for non-simply connected groups

The charges of the twisted branes for strings on the group manifold SU(n)/Z_d are determined. To this end we derive explicit (and remarkably simple) formulae for the relevant NIM-rep coefficients. The charge groups of the twisted and untwisted branes are compared and found to agree for the cases we consider.Comment: 30 page

Voxel-based morphometry (VBM) studies in schizophrenia—can white matter changes be reliably detected with VBM?

Voxel-Based Morphometry (VBM) is a hypothesis-free, whole-brain, voxel-by-voxel analytic method that attempts to compare imaging data between populations. Schizophrenia studies have utilized this method to localize differences in Diffusion Tensor Imaging (DTI) derived Fractional Anisotropy (FA), a measure of white matter integrity, between patients and healthy controls. The number of publications has grown, although it is unclear how reliable and reproducible this method is, given the subtle white matter abnormalities expected in schizophrenia. Here we analyze and combine results from 23 studies published to date that use VBM to study schizophrenia in order to evaluate the reproducibility of this method in DTI analysis. Coordinates of each region reported in DTI VBM studies published thus far in schizophrenia were plotted onto a Montreal Neurological Institute atlas, and their anatomical locations were recorded. Results indicated that the reductions of FA in patients with schizophrenia were scattered across the brain. Moreover, even the most consistently reported regions were reported independently in less than 35% of the papers studied. Other instances of reduced FA were replicated at an even lower rate. Our findings demonstrate striking inconsistency, with none of the regions reported in much more than a third of the published papers. Poor replication rate suggests that the application of VBM to DTI data may not be the optimal way for studying the subtle microstructural abnormalities that are being hypothesized in schizophrenia

Wildfire and Abrupt Ecosystem Disruption on California\u27s Northern Channel Islands at the Allerod-Younger Dryas Boundary (13.0-12.9 ka)

Sedimentary records from California\u27s Northern Channel Islands and the adjacent Santa Barbara Basin (SBB) indicate intense regional biomass burning (wildfire) at the Ållerød–Younger Dryas boundary (~13.0–12.9 ka) (All age ranges in this paper are expressed in thousands of calendar years before present [ka]. Radiocarbon ages will be identified and clearly marked “14C years”.). Multiproxy records in SBB Ocean Drilling Project (ODP) Site 893 indicate that these wildfires coincided with the onset of regional cooling and an abrupt vegetational shift from closed montane forest to more open habitats. Abrupt ecosystem disruption is evident on the Northern Channel Islands at the Ållerød–Younger Dryas boundary with the onset of biomass burning and resulting mass sediment wasting of the landscape. These wildfires coincide with the extinction of Mammuthus exilis [pygmy mammoth]. The earliest evidence for human presence on these islands at 13.1–12.9 ka (~11,000–10,900 14C years) is followed by an apparent 600–800 year gap in the archaeological record, which is followed by indications of a larger-scale colonization after 12.2 ka. Although a number of processes could have contributed to a post 18 ka decline in M. exilis populations (e.g., reduction of habitat due to sea-level rise and human exploitation of limited insular populations), we argue that the ultimate demise of M. exilis was more likely a result of continental scale ecosystem disruption that registered across North America at the onset of the Younger Dryas cooling episode, contemporaneous with the extinction of other megafaunal taxa. Evidence for ecosystem disruption at 13–12.9 ka on these offshore islands is consistent with the Younger Dryas boundary cosmic impact hypothesis [Firestone, R.B., West, A., Kennett, J.P., Becker, L., Bunch, T.E., Revay, Z.S., Schultz, P.H., Belgya, T., Kennett, D.J., Erlandson, J.M., Dickenson, O.J., Goodyear, A.A., Harris, R.S., Howard, G.A., Kloosterman, J.B., Lechler, P., Mayewski, P.A., Montgomery, J., Poreda, R., Darrah, T., Que Hee, S.S., Smith, A.R., Stich, A., Topping, W., Wittke, J.H. Wolbach, W.S., 2007. Evidence for an extraterrestrial impact 12,900 years ago that contributed to the megafaunal extinctions and Younger Dryas cooling. Proceedings of the National Academy of Sciences 104, 16016–16021.]