Exploring block construction and mental imagery: Evidence of atypical orientation discrimination in Williams syndrome

The visuo-spatial perceptual abilities of individuals with Williams syndrome (WS) were investigated in two experiments. Experiment 1 measured the ability of participants to discriminate between oblique and between nonoblique orientations. Individuals with WS showed a smaller effect of obliqueness in response time, when compared to controls matched for non-verbal mental age. Experiment 2 investigated the possibility that this deviant pattern of orientation discrimination accounts for the poor ability to perform mental rotation in WS (Farran et al., 2001). A size transformation task was employed, which shares the image transformation requirements of mental rotation, but not the orientation discrimination demands. Individuals with WS performed at the same level as controls. The results suggest a deviance at the perceptual level in WS, in processing orientation, which fractionates from the ability to mentally transform images

Can electron distribution functions be derived through the Sunyaev-Zel'dovich effect?

Measurements of the Sunyaev-Zel'dovich (hereafter SZ) effect distortion of the cosmic microwave background provide methods to derive the gas pressure and temperature of galaxy clusters. Here we study the ability of SZ effect observations to derive the electron distribution function (DF) in massive galaxy clusters. Our calculations of the SZ effect include relativistic corrections considered within the framework of the Wright formalism and use a decomposition technique of electron DFs into Fourier series. Using multi-frequency measurements of the SZ effect, we find the solution of a linear system of equations that is used to derive the Fourier coefficients; we further analyze different frequency samples to decrease uncertainties in Fourier coefficient estimations. We propose a method to derive DFs of electrons using SZ multi-frequency observations of massive galaxy clusters. We found that the best frequency sample to derive an electron DF includes high frequencies $\nu$=375, 600, 700, 857 GHz. We show that it is possible to distinguish a Juttner DF from a Maxwell-Bolzman DF as well as from a Juttner DF with the second electron population by means of SZ observations for the best frequency sample if the precision of SZ intensity measurements is less than 0.1%. We demonstrate by means of 3D hydrodynamic numerical simulations of a hot merging galaxy cluster that the morphologies of SZ intensity maps are different for frequencies $\nu$=375, 600, 700, 857 GHz. We stress that measurements of SZ intensities at these frequencies are a promising tool for studying electron distribution functions in galaxy clusters.Comment: 11 pages, 12 figures, published in Astronomy and Astrophysic

The association between prior statin usage and long-term outcomes after critical care admission

Background: Statins may have immunomodulatory effects that benefit critically ill patients. Therefore we retrospectively examined the association between survival and the prescription of statins prior to admission to an intensive care unit (ICU), or high dependency unit (HDU), as a result of major elective surgery, or as an emergency with a presumed diagnosis of sepsis. Methods: We retrospectively studied critical care patients (ICU or HDU) from a tertiary referral UK teaching hospital. Nottingham University Hospitals has over 2200 beds, of which 39 are critical care beds. Over a five-year period (2000–2005) 414 patients were identified with a presumed diagnosis of sepsis, and 672 patients were identified with a planned ICU/HDU admission following elective major surgery. Patients prescribed statins prior to hospital admission were compared with those who were not. Demographics, past medical history, drug history, and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were examined. Univariate and multivariate analyses were applied using the primary endpoint of survival at five years after admission. Results: Patients prescribed statins prior to critical care admission were, on average, older, with higher initial APACHE II scores and more pre-existing comorbidities. Statins were almost invariably stopped following admission to critical care. Statin usage was not associated with significantly altered survival during hospital admission, or at five years, for either patients with sepsis (9% v 15%, P=0.121; 73% v 84%, P=0.503 respectively), or post-operative patients (55% v 58%, P=0.762; 57% v 63%, P=0.390). Conclusions: Prior statin usage was not associated with improved or worsening outcomes in patients admitted to critical care after elective surgical cases or with a presumed diagnosis of sepsis

The Cyanobacterial Hepatotoxin Microcystin Binds to Proteins and Increases the Fitness of Microcystis under Oxidative Stress Conditions

Microcystins are cyanobacterial toxins that represent a serious threat to drinking water and recreational lakes worldwide. Here, we show that microcystin fulfils an important function within cells of its natural producer Microcystis. The microcystin deficient mutant ΔmcyB showed significant changes in the accumulation of proteins, including several enzymes of the Calvin cycle, phycobiliproteins and two NADPH-dependent reductases. We have discovered that microcystin binds to a number of these proteins in vivo and that the binding is strongly enhanced under high light and oxidative stress conditions. The nature of this binding was studied using extracts of a microcystin-deficient mutant in vitro. The data obtained provided clear evidence for a covalent interaction of the toxin with cysteine residues of proteins. A detailed investigation of one of the binding partners, the large subunit of RubisCO showed a lower susceptibility to proteases in the presence of microcystin in the wild type. Finally, the mutant defective in microcystin production exhibited a clearly increased sensitivity under high light conditions and after hydrogen peroxide treatment. Taken together, our data suggest a protein-modulating role for microcystin within the producing cell, which represents a new addition to the catalogue of functions that have been discussed for microbial secondary metabolites

The role of the VEGF-C/VEGFR-3 axis in cancer progression

Vascular endothelial growth factor (VEGF) receptor 3 (VEGFR-3) (also called VEGFR-3) is activated by its specific ligand, VEGF-C, which promotes cancer progression. The VEGF-C/VEGFR-3 axis is expressed not only by lymphatic endothelial cells but also by a variety of human tumour cells. Activation of the VEGF-C/VEGFR-3 axis in lymphatic endothelial cells can facilitate metastasis by increasing the formation of lymphatic vessels (lymphangiogenesis) within and around tumours. The VEGF-C/VEGFR-3 axis plays a critical role in leukaemic cell proliferation, survival, and resistance to chemotherapy. Moreover, activation of the VEGF-C/VEGFR-3 axis in several types of solid tumours enhances cancer cell mobility and invasion capabilities, promoting cancer cell metastasis. In this review, we discuss the novel function and molecular mechanism of the VEGF-C/VEGFR-3 axis in cancer progression

Impacts of excision repair cross-complementing gene 1 (ERCC1), dihydropyrimidine dehydrogenase, and epidermal growth factor receptor on the outcomes of patients with advanced gastric cancer

Using laser-captured microdissection and a real-time RT–PCR assay, we quantitatively evaluated mRNA levels of the following biomarkers in paraffin-embedded gastric cancer (GC) specimens obtained by surgical resection or biopsy: excision repair cross-complementing gene 1 (ERCC1), dihydropyrimidine dehydrogenase (DPD), methylenetetrahydrofolate reductase (MTHFR), epidermal growth factor receptor (EGFR), and five other biomarkers related to anticancer drug sensitivity. The study group comprised 140 patients who received first-line chemotherapy for advanced GC. All cancer specimens were obtained before chemotherapy. In patients who received first-line S-1 monotherapy (69 patients), low MTHFR expression correlated with a higher response rate (low: 44.9% vs high: 6.3%; P=0.006). In patients given first-line cisplatin-based regimens (combined with S-1 or irinotecan) (43 patients), low ERCC1 correlated with a higher response rate (low: 55.6% vs high: 18.8%; P=0.008). Multivariate survival analysis of all patients demonstrated that high ERCC1 (hazard ratio (HR): 2.38 (95% CI: 1.55–3.67)), high DPD (HR: 2.04 (1.37–3.02)), low EGFR (HR: 0.34 (0.20–0.56)), and an elevated serum alkaline phosphatase level (HR: 1.00 (1.001–1.002)) were significant predictors of poor survival. Our results suggest that these biomarkers are useful predictors of clinical outcomes in patients with advanced GC

First international consensus on the methodology of lymphangiogenesis quantification in solid human tumours

The lymphatic system is the primary pathway of metastasis for most human cancers. Recent research efforts in studying lymphangiogenesis have suggested the existence of a relationship between lymphatic vessel density and patient survival. However, current methodology of lymphangiogenesis quantification is still characterised by high intra- and interobserver variability. For the amount of lymphatic vessels in a tumour to be a clinically useful parameter, a reliable quantification technique needs to be developed. With this consensus report, we therefore would like to initiate discussion on the standardisation of the immunohistochemical method for lymphangiogenesis assessment