A model for the fast ionic diffusion in alumina-doped LiI

Lithium Iodide shows enhanced ionic conductivity when doped with a powder of the insulator, alumina. We extend Landauer's effective medium model to see if the observations are consistent with a high conductivity layer forming on each non-conducting particle. The predictions are consistent with experiment provided one assumes the layer a few hundred Angstroms thick. At the outside, away from the particle, the enhancement of conductivity should fall off slowly, as in Debye-Huckel screening, whereas it is possible a new phase forms close to the insulator surface

Upper Eocene planktonic foraminifera from northern Saudi Arabia: implications for stratigraphic ranges

The Rashrashiyah Formation of the Sirhan Basin in northern Saudi Arabia contains diverse assemblages of planktonic foraminifera. We examined the biostratigraphy, stratigraphic range and preservation of upper Eocene planktonic foraminifera. Assemblages are well-preserved and diverse, with 40 species and 11 genera. All samples are assigned to the Priabonian Globigerinatheka semiinvoluta Highest Occurrence Zone (E14), consistent with calcareous nannofossil biostratigraphy indicating Zone CNE17. Well-preserved planktonic foraminifera assemblages from the lower part of the upper Eocene are rare worldwide. Our study provides new insights into the stratigraphic ranges of many species. We find older (Zone E14) stratigraphic occurrences of several species of Globoturborotalita previously thought to have evolved in the latest Eocene (Zone E15, E16) or Oligocene; these include G. barbula, G. cancellata, G. gnaucki, G. pseudopraebulloides, and G. paracancellata. Older stratigraphic occurrences for Dentoglobigerina taci and Subbotina projecta are also found, and Globigerinatheka kugleri occurs at a younger stratigraphic level than previously proposed. Our revisions to stratigraphic ranges indicate that the late Eocene had a higher tropical–subtropical diversity of planktonic foraminifera than hitherto reported

Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis: a systematic review

<p>Abstract</p> <p>Background</p> <p>Cannabis therapy has been considered an effective treatment for spasticity, although clinical reports of symptom reduction in multiple sclerosis (MS) describe mixed outcomes. Recently introduced therapies of combined Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD) extracts have potential for symptom relief with the possibility of reducing intoxication and other side effects. Although several past reviews have suggested that cannabinoid therapy provides a therapeutic benefit for symptoms of MS, none have presented a methodical investigation of newer cannabinoid treatments in MS-related spasticity. The purpose of the present review was to systematically evaluate the effectiveness of combined THC and CBD extracts on MS-related spasticity in order to increase understanding of the treatment's potential effectiveness, safety and limitations.</p> <p>Methods</p> <p>We reviewed MEDLINE/PubMed, Ovid, and CENTRAL electronic databases for relevant studies using randomized controlled trials. Studies were included only if a combination of THC and CBD extracts was used, and if pre- and post-treatment assessments of spasticity were reported.</p> <p>Results</p> <p>Six studies were systematically reviewed for treatment dosage and duration, objective and subjective measures of spasticity, and reports of adverse events. Although there was variation in the outcome measures reported in these studies, a trend of reduced spasticity in treated patients was noted. Adverse events were reported in each study, however combined TCH and CBD extracts were generally considered to be well-tolerated.</p> <p>Conclusion</p> <p>We found evidence that combined THC and CBD extracts may provide therapeutic benefit for MS spasticity symptoms. Although some objective measures of spasticity noted improvement trends, there were no changes found to be significant in post-treatment assessments. However, subjective assessment of symptom relief did often show significant improvement post-treatment. Differences in assessment measures, reports of adverse events, and dosage levels are discussed.</p

Equatorial Pacific productivity changes near the Eocene-Oligocene boundary

There is general agreement that productivity in high latitudes increased in the late Eocene and remained high in the early Oligocene. Evidence for both increased and decreased productivity across the Eocene-Oligocene transition (EOT) in the tropics has been presented, usually based on only one paleoproductivity proxy and often in sites with incomplete recovery of the EOT itself. A complete record of the Eocene-Oligocene transition was obtained at three drill sites in the eastern equatorial Pacific Ocean (ODP Site 1218 and IODP Sites U1333 and U1334). Four paleoproductivity proxies that have been examined at these sites, together with carbon and oxygen isotope measurements on early Oligocene planktonic foraminifera, give evidence of ecologic and oceanographic change across this climatically important boundary. Export productivity dropped sharply in the basal Oligocene (~33.7 Ma) and only recovered several hundred thousand years later; however, overall paleoproductivity in the early Oligocene never reached the average levels found in the late Eocene and in more modern times. Changes in the isotopic gradients between deep- and shallow-living planktonic foraminifera suggest a gradual shoaling of the thermocline through the early Oligocene that, on average, affected accumulation rates of barite, benthic foraminifera, and opal, as well as diatom abundance near 33.5 Ma. An interval with abundant large diatoms beginning at 33.3 Ma suggests an intermediate thermocline depth, which was followed by further shoaling, a dominance of smaller diatoms, and an increase in average primary productivity as estimated from accumulation rates of benthic foraminifera

Transpiration from subarctic deciduous woodlands: environmental controls and contribution to ecosystem evapotranspiration

Potential land‐climate feedbacks in subarctic regions, where rapid warming is driving forest expansion into the tundra, may be mediated by differences in transpiration of different plant functional types. Here we assess the environmental controls of overstorey transpiration and its relevance for ecosystem evapotranspiration in subarctic deciduous woodlands. We measured overstorey transpiration of mountain birch canopies and ecosystem evapotranspiration in two locations in northern Fennoscandia, having dense (Abisko) and sparse (Kevo) overstories. For Kevo, we also upscale chamber‐measured understorey evapotranspiration from shrubs and lichen using a detailed land cover map. Sub‐daily evaporative fluxes were not affected by soil moisture, and showed similar controls by vapour pressure deficit and radiation across sites. At the daily timescale, increases in evaporative demand led to proportionally higher contributions of overstorey transpiration to ecosystem evapotranspiration. For the entire growing season, the overstorey transpired 33% of ecosystem evapotranspiration in Abisko and only 16% in Kevo. At this latter site, the understorey had a higher leaf area index and contributed more to ecosystem evapotranspiration compared to the overstorey birch canopy. In Abisko, growing season evapotranspiration was 27% higher than precipitation, consistent with a gradual soil moisture depletion over the summer. Our results show that overstorey canopy transpiration in subarctic deciduous woodlands is not the dominant evaporative flux. However, given the observed environmental sensitivity of evapotranspiration components, the role of deciduous trees in driving ecosystem evapotranspiration may increase with the predicted increases in tree cover and evaporative demand across subarctic regions

Perfectionism and eating disorder symptoms in female university students: The central role of perfectionistic self-presentation

Purpose: Numerous studies have found perfectionism to show positive relations with eating disorder symptoms, but so far no study has examined whether perfectionistic self-presentation can explain these relations or whether the relations are the same for different eating disorder symptom groups. Methods: A sample of 393 female university students completed self-report measures of perfectionism (self-oriented perfectionism, socially prescribed perfectionism), perfectionistic self-presentation (perfectionistic self-promotion, nondisplay of imperfection, nondisclosure of imperfection), and three eating disorder symptom groups (dieting, bulimia, oral control). In addition, students reported their weight and height so their body mass index (BMI) could be computed. Results: Results of multiple regression analyses controlling for BMI indicated that socially prescribed perfectionism positively predicted all three symptom groups, whereas self-oriented perfectionism positively predicted dieting only. Moreover, perfectionistic self-presentation explained the positive relations that perfectionism showed with dieting and oral control, but not with bulimia. Further analyses indicated that all three aspects of perfectionistic self-presentation positively predicted dieting, whereas only nondisclosure of imperfection positively predicted bulimia and oral control. Overall, perfectionistic self-presentation explained 10.4-23.5% of variance in eating disorder symptoms, whereas perfectionism explained 7.9-12.1%. Conclusions: The findings suggest that perfectionistic self-presentation explains why perfectionistic women show higher levels of eating disorder symptoms, particularly dieting. Thus perfectionistic self-presentation appears to play a central role in the relations of perfectionism and disordered eating and may warrant closer attention in theory, research, and treatment of eating and weight disorders

MAGE-A cancer/testis antigens inhibit MDM2 ubiquitylation function and promote increased levels of MDM4

Melanoma antigen A (MAGE-A) proteins comprise a structurally and biochemically similar sub-family of Cancer/Testis antigens that are expressed in many cancer types and are thought to contribute actively to malignancy. MAGE-A proteins are established regulators of certain cancer-associated transcription factors, including p53, and are activators of several RING finger-dependent ubiquitin E3 ligases. Here, we show that MAGE-A2 associates with MDM2, a ubiquitin E3 ligase that mediates ubiquitylation of more than 20 substrates including mainly p53, MDM2 itself, and MDM4, a potent p53 inhibitor and MDM2 partner that is structurally related to MDM2. We find that MAGE-A2 interacts with MDM2 via the N-terminal p53-binding pocket and the RING finger domain of MDM2 that is required for homo/hetero-dimerization and for E2 ligase interaction. Consistent with these data, we show that MAGE-A2 is a potent inhibitor of the E3 ubiquitin ligase activity of MDM2, yet it does not have any significant effect on p53 turnover mediated by MDM2. Strikingly, however, increased MAGE-A2 expression leads to reduced ubiquitylation and increased levels of MDM4. Similarly, silencing of endogenous MAGE-A expression diminishes MDM4 levels in a manner that can be rescued by the proteasomal inhibitor, bortezomid, and permits increased MDM2/MDM4 association. These data suggest that MAGE-A proteins can: (i) uncouple the ubiquitin ligase and degradation functions of MDM2; (ii) act as potent inhibitors of E3 ligase function; and (iii) regulate the turnover of MDM4. We also find an association between the presence of MAGE-A and increased MDM4 levels in primary breast cancer, suggesting that MAGE-A-dependent control of MDM4 levels has relevance to cancer clinically

The degradation of p53 and its major E3 ligase Mdm2 is differentially dependent on the proteasomal ubiquitin receptor S5a.

p53 and its major E3 ligase Mdm2 are both ubiquitinated and targeted to the proteasome for degradation. Despite the importance of this in regulating the p53 pathway, little is known about the mechanisms of proteasomal recognition of ubiquitinated p53 and Mdm2. In this study, we show that knockdown of the proteasomal ubiquitin receptor S5a/PSMD4/Rpn10 inhibits p53 protein degradation and results in the accumulation of ubiquitinated p53. Overexpression of a dominant-negative deletion of S5a lacking its ubiquitin-interacting motifs (UIM)s, but which can be incorporated into the proteasome, also causes the stabilization of p53. Furthermore, small-interferring RNA (siRNA) rescue experiments confirm that the UIMs of S5a are required for the maintenance of low p53 levels. These observations indicate that S5a participates in the recognition of ubiquitinated p53 by the proteasome. In contrast, targeting S5a has no effect on the rate of degradation of Mdm2, indicating that proteasomal recognition of Mdm2 can be mediated by an S5a-independent pathway. S5a knockdown results in an increase in the transcriptional activity of p53. The selective stabilization of p53 and not Mdm2 provides a mechanism for p53 activation. Depletion of S5a causes a p53-dependent decrease in cell proliferation, demonstrating that p53 can have a dominant role in the response to targeting S5a. This study provides evidence for alternative pathways of proteasomal recognition of p53 and Mdm2. Differences in recognition by the proteasome could provide a means to modulate the relative stability of p53 and Mdm2 in response to cellular signals. In addition, they could be exploited for p53-activating therapies. This work shows that the degradation of proteins by the proteasome can be selectively dependent on S5a in human cells, and that this selectivity can extend to an E3 ubiquitin ligase and its substrate