The neurotoxicity of 5-S-cysteinyldopamine is mediated by the early activation of ERK1/2 followed by the subsequent activation of ASK1/JNK1/2 pro-apoptotic signalling

Parkinson's disease is characterized by the progressive and selective loss of dopaminergic neurons in the substantia nigra. It has been postulated that endogenously formed CysDA (5-S-cysteinyldopamine) and its metabolites may be, in part, responsible for this selective neuronal loss, although the mechanisms by which they contribute to such neurotoxicity are not understood. Exposure of neurons in culture to CysDA caused cell injury, apparent 12-48 h post-exposure. A portion of the neuronal death induced by CysDA was preceded by a rapid uptake and intracellular oxidation of CysDA, leading to an acute and transient activation of ERK2 (extracellular-signal-regulated kinase 2) and caspase 8. The oxidation of CysDA also induced the activation of apoptosis signal-regulating kinase 1 via its de-phosphorylation at Ser967, the phosphorylation of JNK (c-Jun N-terminal kinase) and c-Jun (Ser73) as well as the activation of p38, caspase 3, caspase 8, caspase 7 and caspase 9. Concurrently, the inhibition of complex I by the dihydrobenzothiazine DHBT-1 [7-(2-aminoethyl)-3,4-dihydro-5-hydroxy-2H-1,4-benzothiazine-3-carboxylic acid], formed from the intracellular oxidation of CysDA, induces complex I inhibition and the subsequent release of cytochrome c which further potentiates pro-apoptotic mechanisms. Our data suggest a novel comprehensive mechanism for CysDA that may hold relevance for the selective neuronal loss observed in Parkinson's disease.

Interdecadal changes on the seasonal prediction of the western North Pacific summer climate around the late 1970s and early 1990s

Identifying predictability and the corresponding sources for the western North Pacific (WNP) summer climate in the case of non-stationary teleconnections during recent decades benefits for further improvements of long-range prediction on the WNP and East Asian summers. In the past few decades, pronounced increases on the summer sea surface temperature (SST) and associated interannual variability are observed over the tropical Indian Ocean and eastern Pacific around the late 1970s and over the Maritime Continent and western–central Pacific around the early 1990s. These increases are associated with significant enhancements of the interannual variability for the lower-tropospheric wind over the WNP. In this study, we further assess interdecadal changes on the seasonal prediction of the WNP summer anomalies, using May-start retrospective forecasts from the ENSEMBLES multi-model project in the period 1960–2005. It is found that prediction of the WNP summer anomalies exhibits an interdecadal shift with higher prediction skills since the late 1970s, particularly after the early 1990s. Improvements of the prediction skills for SSTs after the late 1970s are mainly found around tropical Indian Ocean and the WNP. The better prediction of the WNP after the late 1970s may arise mainly from the improvement of the SST prediction around the tropical eastern Indian Ocean. The close teleconnections between the tropical eastern Indian Ocean and WNP summer variability work both in the model predictions and observations. After the early 1990s, on the other hand, the improvements are detected mainly around the South China Sea and Philippines for the lower-tropospheric zonal wind and precipitation anomalies, associating with a better description of the SST anomalies around the Maritime Continent. A dipole SST pattern over the Maritime Continent and the central equatorial Pacific Ocean is closely related to the WNP summer anomalies after the early 1990s. This teleconnection mode is quite predictable, which is realistically reproduced by the models, presenting more predictable signals to the WNP summer climate after the early 1990s.

'The debatable territory where geology and archaeology meet': reassessing the early archaeobotanical work of Clement Reid and Arthur Lyell at Roman Silchester

The first large-scale archaeobotanical study in Britain, conducted from 1899 to 1909 by Clement Reid and Arthur Lyell at Silchester, provided the first evidence for the introduction of Roman plant foods to Britain, yet the findings have thus far remained unverified. This paper presents a reassessment of these archaeobotanical remains, now stored as part of the Silchester Collection in Reading Museum. The documentary evidence for the Silchester study is summarised, before the results are presented for over a 1000 plant remains including an assessment of preservation, identification and modern contamination. The dataset includes both evidence for the presence of nationally rare plant foods, such as medlar, and several archaeophytes. The methodologies and original interpretations of Reid and Lyell’s study are reassessed in light of current archaeobotanical knowledge. Spatial and contextual patterns in the distribution of plant foods and ornamental taxa are also explored. Finally, the legacy of the study for the development of archaeobotany in the 20th century is evaluated.

The “Great Queen of Lightninge Flashes”: the transmission of female-voiced burlesque poetry in the early seventeenth century

The essay uncovers evidence for the construction of the ‘woman author’ in the largely male vogue for bawdy burlesque poetry by tracing the circulation of a pair of verses through seventeenth-century manuscript and print miscellanies. It argues that just as these verses are reworked and recontextualised through the process of transmission, so to their ‘authors’ are re-embodied and ascribed different identities in different publication contexts. Female-voiced bawdy poetry raises particular problems for authorial attribution, rather than searching for the real woman behind the text, the essay examines how the ‘authors’ of female-voiced bawdy poetry were produced and reproduced through shifting formal frameworks and socioliterary networks.

Comparison of biological behavior between early-stage adenocarcinoma and squamous cell carcinoma of the uterine cervix

Objectives: (1) To compare the anatomopathological variables and recurrence rates in patients with early-stage adenocarcinoma (AC) and squamous cell carcinoma (SCC) of the uterine cervix; (2) to identify the independent risk factors for recurrence. Study design: This historical cohort study assessed 238 patients with carcinoma of the uterine cervix (113 and IIA), who underwent radical hysterectomy with pelvic lymph node dissection between 1980 and 1999. Comparison of category variables between the two histological types was carried out using the Pearson`s X-2 test or Fisher exact test. Disease-free survival rates for AC and SCC were calculated using the Kaplan-Meier method and the curves were compared using the log-rank test. The Cox proportional hazards model was used to identify the independent risk factors for recurrence. Results: There were 35 cases of AC (14.7%) and 203 of SCC (85.3%). AC presented lower histological grade than did SCC (grade 1: 68.6% versus 9.4%; p < 0.001), lower rate of lymphovascular space involvement (25.7% versus 53.7%; p = 0.002), lower rate of invasion into the middle or deep thirds of the uterine cervix (40.0% versus 80.8%; p < 0.001) and lower rate of lymph node metastasis (2.9% versus 16.3%; p = 0.036). Although the recurrence rate was lower for AC than for SCC (11.4% versus 15.8%), this difference was not statistically significant (p = 0.509). Multivariate analysis identified three independent risk factors for recurrence: presence of metastases in the pelvic lymph nodes, invasion of the deep third of the uterine cervix and absence of or slight inflammatory reaction in the cervix. When these variables were adjusted for the histological type and radiotherapy status, they remained in the model as independent risk factors. Conclusion: The AC group showed less aggressive histological behavior than did the SCC group, but no difference in the disease-free survival rates was noted. (C) 2006 Elsevier Ireland Ltd. All rights reserved.

Effects of long-term diabetes on the structure and cell proliferation of the myometrium in the early pregnancy of mice

P>It is known that the development of diabetic complications in human pregnancy is directly related to the severity and the duration of this pathology. In this study, we developed a model of long-term type 1 diabetes to investigate its effects on the cytoarchitecture, extracellular matrix and cell proliferation during the first adaptation phase of the myometrium for pregnancy. A single dose of alloxan was used to induce diabetes in mice prior to pregnancy. To identify the temporal effects of diabetes the mice were divided into two groups: Group D1 (females that became pregnant 90-100 days after alloxan); Group D2 (females that became pregnant 100-110 days after alloxan). Uterine samples were collected after 168 h of pregnancy and processed for light and electron microscopy. In both groups the histomorphometric evaluation showed that diabetes promoted narrowing of the myometrial muscle layers which was correlated with decreased cell proliferation demonstrated by PCNA immunodetection. In D1, diabetes increased the distance between muscle layers and promoted oedema. Contrarily, in D2 the distance between muscle layers decreased and, instead of oedema, there was a markedly deposition of collagen in the myometrium. Ultrastructural analysis showed that diabetes affects the organization of the smooth muscle cells and their myofilaments. Consistently, the immunoreaction for smooth muscle alpha-actin revealed clear disorganization of the contractile apparatus in both diabetic groups. In conclusion, the present model demonstrated that long-term diabetes promotes significant alterations in the myometrium in a time-sensitive manner. Together, these alterations indicate that diabetes impairs the first phenotypic adaptation phase of the pregnant myometrium.

Deiodinase-mediated thyroid hormone inactivation minimizes thyroid hormone signaling in the early development of fetal skeleton

Thyroid hormone (TH) plays a key role on post-natal bone development and metabolism, while its relevance during fetal bone development is uncertain. To Study this, pregnant once were made hypothyroid and fetuses harvested at embryonic days (E) 12.5, 14.5, 16.5 and 18.5. Despite a marked reduction in fetal tissue concentration of both T4 and T3, bone development, as assessed at the distal epiphyseal growth plate of the femur and vertebra, was largely preserved Lip to E16.5. Only at E18.5, the hypothyroid fetuses exhibited a reduction in femoral type I and type X collagen and osteocalcin mRNA levels, in the length and area of the proliferative and hypertrophic zones, in the number of chondrocytes per proliferative column, and in the number of hypertrophic chondrocyres, in addition to a slight delay in endochondral and intramembranous ossification. This Suggests that LIP to E 16.5, thyroid hormone signaling in bone is kept to a minimum. In fact, measuring the expression level of the activating and inactivating iodothyronine deiodinases (D2 and D3) helped understand how this is achieved. D3 mRNA was readily detected as early as E14.5 and its expression decreased markedly (similar to 10-fold) at E18.5, and even more at 14 days after birth (P14). In contrast. D2 mRNA expression increased significantly by E18.5 and markedly (similar to 2.5-fold) by P14. The reciprocal expression levels of D2 and D3 genes during early bone development along with the absence of a hypothyroidism-induced bone phenotype at this time Suggest that coordinated reciprocal deiodinase expression keeps thyroid hormone signaling in bone to very low levels at this early stage of bone development. (c) 2008 Elsevier Inc. All rights reserved.

Signature of the interaction between dark energy and dark matter in galaxy clusters

We investigate the influence of ail interaction between dark energy and dark matter upon the dynamics of galaxy clusters. We obtain file general Layser-Irvine equation in the presence of interactions, and find how, in that case. the virial theorem stands corrected. Using optical, X-ray and weak lensing data from 33 relaxed galaxy clusters, we put constraints on the strength of the coupling between the dark sectors. Available data Suggests that this coupling is small but positive, indicating that dark energy might be decaying into dark matter. Systematic effects between the several mass estimates, however, should be better known, before definitive conclusions oil the magnitude and significance of this coupling could be established. (C) 2009 Published by Elsevier B.V.

Thermodynamical description of the interaction between holographic dark energy and dark matter

We present a thermodynamical description of the interaction between holographic dark energy and dark matter. If holographic dark energy and dark matter evolve separately, each of them remains in thermodynamic equilibrium. A small interaction between them may be viewed as a stable thermal fluctuation that brings a logarithmic correction to the equilibrium entropy. From this correction we obtain a physical expression for the interaction which is consistent with phenomenological descriptions and passes reasonably well the observational tests: (c) 2008 Elsevier B.V. All rights reserved.

Longitudinal scaling property of the charge balance function in Au plus Au collisions at root s(NN)=200 GeV

We present measurements of the charge balance function, from the charged particles, for diverse pseudorapidity and transverse momentum ranges in Au + Au collisions at root S(NN) = 200 GeV using the STAR detector at RHIC. We observe that the balance function is boost-invariant within the pseudorapidity coverage vertical bar-1.3, 1.3 vertical bar. The balance function properly scaled by the width of the observed pseudorapidity window does not depend on the position or size of the pseudorapidity window. This scaling property also holds for particles in different transverse momentum ranges. In addition, we find that the width of the balance function decreases monotonically with increasing transverse momentum for all centrality classes. (c) 2010 Elsevier B.V. All rights reserved.

Update on the correlation of the highest energy cosmic rays with nearby extragalactic matter

Data collected by the Pierre Auger Observatory through 31 August 2007 showed evidence for anisotropy in the arrival directions of cosmic rays above the Greisen-Zatsepin-Kuz`min energy threshold, 6 x 10(19) eV. The anisotropy was measured by the fraction of arrival directions that are less than 3.1 degrees from the position of an active galactic nucleus within 75 Mpc (using the Veron-Cetty and Veron 12th catalog). An updated measurement of this fraction is reported here using the arrival directions of cosmic rays recorded above the same energy threshold through 31 December 2009. The number of arrival directions has increased from 27 to 69, allowing a more precise measurement. The correlating fraction is (38(-6)(+7))%, compared with 21% expected for isotropic cosmic rays. This is down from the early estimate of (69-(+11)(13))%. The enlarged set of arrival directions is examined also in relation to other populations of nearby extragalactic objects: galaxies in the 2 Microns All Sky Survey and active galactic nuclei detected in hard X-rays by the Swift Burst Alert Telescope. A celestial region around the position of the radiogalaxy Cen A has the largest excess of arrival directions relative to isotropic expectations. The 2-point autocorrelation function is shown for the enlarged set of arrival directions and compared to the isotropic expectation. (C) 2010 Elsevier B.V. All rights reserved.

Chondrichthyans from the base of the Irati Formation (Early Permian, Parana Basin), Sao Paulo, Brazil

Three species of chondrichthyans are reported from conglomeratic sandstone at the base of the Lower Permian (Artinskian) Irati Formation (Parana Basin) near Rio Claro, Sao Paulo State, Brazil. The fossils include: 1) dispersed teeth of the petalodont ltapyrodus punctatus Silva Santos 1990, first described from the Permian (Artinskian) Pedra do Fogo Formation, Parnaiba Basin, Northeast Brazil; 2) a new species of tooth of the Order Orodontiformes; and 3) a new species of finspine of the Order Ctenacanthiformes. These fossils occur in an allochthonous assemblage of vertebrate remains including other Chondrichthyes, Xenacanthiformes and cladodonts, paleonisciform bony fish, and tetrapods. This discovery is a significant contribution to the sparse record of South American Chondrichthyes from the Early Permian and raises questions regarding the paleoenvironmental adaptations among these fish within Paleozoic basins of Brazil at this time. (C) 2010 International Association for Gondwana Research. Published by Elsevier B.V. All rights reserved.