Differential regulation of the Wilms' tumor gene, WT1, during differentiation of embryonal carcinoma and embryonic stem cells.

The expression pattern of the Wilms' tumor suppressor gene, WT1, during embryonal development suggests a role for the WT1 proteins in the differentiation of specific tissues. This notion is supported by the observation that WT1 knock-out mice fall to develop kidneys and gonads. We describe here the changes in the expression and DNA binding activity of the WT1 gene product in P19 embryonal carcinoma cells and embryonic stem cells triggered to differentiate by either retinoic acid (RA) or DMSO. In exponentially growing P19 embryonal carcinoma (EC) cells, WT1 mRNA and proteins were undetectable. During RA-induced but not DMSO-induced differentiation of P19 EC cells, WT1 expression and DNA binding are strongly activated. Treatment of embryonic stem cells with RA resulted in a similar activation of WT1. Immunohistochemical analysis showed that WT1 is expressed in endodermal, glial, and epithelial cell types. In addition, DNA binding by EGR-1, a transcription factor structurally related to WT1, increased during differentiation of P19 EC and embryonic stem cells. To investigate the possible functional consequences of DNA binding by WT1, we examined the expression levels of two putative transcriptional targets of WT1, the insulin-like growth factor 1 receptor and epidermal growth factor receptor. We found that after an initial induction, decreasing expression of the insulin-like growth factor I receptor is correlated with increasing WT1 expression. Our results demonstrate that expression of WT1 is induced in specific cell types during RA-induced differentiation of P19 EC cells, reflecting the tissue-specific expression of WT1 in vivo. Therefore, we believe that P19 EC cells are a suitable system to study activation and function of WT1 during differentiation

Inter-muscular coherence in speed skaters with skater's cramp

Introduction: Skater's cramp is a career-ending movement disorder in expert speed skaters noted to be a likely task-specific dystonia. In other movement disorders, including task-specific dystonia, studies have found evidence of central dysregulation expressed as higher inter-muscular coherence. We looked at whether inter-muscular coherence was higher in affected skaters as a possible indicator that it is centrally driven, and by extension further evidence it is a task-specific dystonia.Methods: In 14 affected and 14 control skaters we calculated inter-muscular coherence in the theta-band in a stationary task where tonic muscle activation was measured at 10%, 20% and 50% of maximum voluntary contraction. Additionally, we calculated wavelet coherence while skating at key moments in the stroke cycle.Results: Coherence did not differ in the stationary activation task. While skating, coherence was higher in the impacted leg of affected skaters compared to their non-impacted leg, p = .05, η2 = 0.031, and amplitude of electromyography correlated with coherence in the impacted leg, p = .009, R2adjusted = 0.41. A sub-group of severely affected skaters (n = 6) had higher coherence in the impacted leg compared to the left and right leg of controls, p = .02, Cohen's d = 1.59 and p = .01, Cohen's d = 1.63 respectively. Results were less clear across the entire affected cohort probably due to a diverse case-mix.Conclusion: Our results of higher coherence in certain severe cases of skater's cramp is preliminary evidence of a central dysregulation, making the likelihood it is a task-specific dystonia higher.</p

Molecular and functional analysis of the XPBC/ERCC-3 promoter: Transcription activity is dependent on the integrity of an Sp1 binding element.

The human XPBC/ERCC-3 gene, which corrects the excision-repair defect in xeroderma pigmentosum group B cells and the UV-sensitive CHO mutant 27-1 cells, appears to be expressed constitutively in various cell types and tissues. We have analysed the structure and functionality of the XPBC/ERCC-3 promoter. Transcription of the XPBC/ERCC-3 gene is initiated from heterogeneous sites, with a major startpoint mapped at position -54 (relative to the translation start codon ATG). The promoter region does not possess classical TATA and CAAT elements, but it is GC-rich and contains three putative Sp1-binding sites. In addition, there are two elements related to the cyclic AMP (cAMP)-response element (CRE) and the 12-O-tetradecanoyl phorbol-13-acetate-response element (TRE) in the 5'-flanking reg

Muscular and kinematic features in speed skaters indicate a task-specific dystonia

Objective: Skater's cramp is a movement disorder in speed skaters. We investigated whether affected skaters matched the disease profile of task-specific dystonia, specifically whether there was evidence of maladaptive muscle activity occurring simultaneously with aberrant movements (jerking). We further examined different skating intensities, positing no change would be more indicative of task-specific dystonia. Methods: We analyzed video, kinematic and muscle activity in 14 affected skaters. We measured the angular velocity and electromyographic activity of normalized speed skating strokes using one dimensional statistical non-parametric mapping. Skaters were matched with comparably skilled controls, and filled out a bespoke clinical questionnaire. Results: Skaters’ impacted leg showed over-activation in the peroneus longus, tibialis anterior and gastrocnemius that coincided with higher foot movement compared to their healthy leg and controls. This pattern persisted regardless of skating intensity. Clinical features indicated it was task-specific and painless with common trigger factors including stress, equipment change, and falling. Conclusions: We showed aberrant muscular and kinematic activity in a movement disorder in speed skaters indicative of task-specific dystonia. Significance: Understanding skater's cramp as a task-specific dystonia could reduce the damage that misdiagnosis and unsuccessful invasive operations have caused. Our quantitative method has value in testing future treatment efficacy.</p

Heavy Carriers and Non-Drude Optical Conductivity in MnSi

Optical properties of the weakly helimagnetic metal MnSi have been determined in the photon energy range from 2 meV to 4.5 eV using the combination of grazing incidence reflectance at 80 degrees (2 meV to 0.8 eV) and ellipsometry (0.8 to 4.5 eV). As the sample is cooled below 100 K the effective mass becomes strongly frequency dependent at low frequencies, while the scattering rate developes a linear frequency dependence. The complex optical conductivity can be described by the phenomenological relation \sigma(\omega,T) \propto (\Gamma(T)+i\omega)^{-1/2} used for cuprates and ruthenates.Comment: 5 pages, ReVTeX 4, 5 figures in eps forma

Habitat quality, configuration and context effects on roe deer fecundity across a forested landscape mosaic

Effective landscape-scale management of source-sink deer populations will be strengthened by understanding whether local variation in habitat quality drives heterogeneity in productivity. We related female roe deer Capreolus capreolus fecundity and body mass to habitat composition and landscape context, separately for adults and yearlings, using multi-model inference (MMI) applied to a large sample of individuals (yearlings: fecundity=202, body mass=395; adults: fecundity=908, body mass=1669) culled during 2002-2015 from an extensive (195 km2) heterogeneous forest landscape. Adults were heavier (inter-quartile, IQ, effect size=+0.5kg) when culled in buffers comprising more arable lands while contrary to our prediction no effects on body mass of grassland, young forest or access to vegetation on calcareous soil were found. Heavier adults were more fertile (IQ effect size, +12% probability of having two embryos instead of one or zero). Counter-intuitively, adults with greater access to arable lands were less fecund (IQ effect of arable: -7% probability of having two embryos, instead of one or zero), and even accounting for greater body mass of adults with access to arable, their modelled fecundity was similar to or lower than that of adults in the forest interior. In contrast, effects of grassland, young forest and calcareous soil did not receive support. Yearling body mass had an effect on fecundity twice that found in adults (+23% probability of having one additional embryo), but yearling body mass and fecundity were not affected by any candidate habitat or landscape variables. Effect of arable lands on body mass and fecundity were small, with little variance explained (Coefficient of Variation of predicted fecundity across forest sub-regions=0.03 for adults). More variance in fecundity was attributed to other differences between forest management sub-regions (modelled as random effects), suggesting other factors might be important. When analysing source-sink population dynamics to support management, an average value of fecundity can be appropriate across a heterogeneous forest landscape

Personalized peptide-based vaccination for treatment of colorectal cancer: rational and progress

Colorectal cancer (CRC) is one of the most common cancers globally and is associated with a high rate of morbidity and mortality. A large proportion of patients with early stage CRC who undergo conventional treatments develop local recurrence or distant metastasis and in this group of advanced disease, the survival rate is low. Furthermore there is often a poor response and/or toxicity associated with chemotherapy and chemo-resistance may limit continuing conventional treatment alone. Choosing novel and targeted therapeutic approaches based on clinicopathological and molecular features of tumors in combination with conventional therapeutic approach could be used to eradicate residual micrometastasis and therefore improve patient prognosis and also be used preventively. Peptide-based vaccination therapy is one class of cancer treatment that could be used to induce tumor-specific immune responses, through the recognition of specific antigen-derived peptides in tumor cells, and this has emerged as a promising anti-cancer therapeutic strategy. The aim of this review was to summarize the main findings of recent studies in exciting field of peptide-based vaccination therapy in CRC patients as a novel therapeutic approach in treatment of CRC