The structure of an LIM-only protein 4 (LMO4) and deformed epidermal autoregulatory factor-1 (DEAF1) complex reveals a common mode of binding to LMO4

LIM-domain only protein 4 (LMO4) is a widely expressed protein with important roles in embryonic development and breast cancer. It has been reported to bind many partners, including the transcription factor Deformed epidermal autoregulatory factor-1 (DEAF1), with which LMO4 shares many biological parallels. We used yeast two-hybrid assays to show that DEAF1 binds both LIM domains of LMO4 and that DEAF1 binds the same face on LMO4 as two other LMO4-binding partners, namely LIM domain binding protein 1 (LDB1) and C-terminal binding protein interacting protein (CtIP/RBBP8). Mutagenic screening analysed by the same method, indicates that the key residues in the interaction lie in LMO4LIM2 and the N-terminal half of the LMO4-binding domain in DEAF1. We generated a stable LMO4LIM2-DEAF1 complex and determined the solution structure of that complex. Although the LMO4-binding domain from DEAF1 is intrinsically disordered, it becomes structured on binding. The structure confirms that LDB1, CtIP and DEAF1 all bind to the same face on LMO4. LMO4 appears to form a hub in protein-protein interaction networks, linking numerous pathways within cells. Competitive binding for LMO4 therefore most likely provides a level of regulation between those different pathways.SJ was funded by an Australian Postgraduate Award (education.gov.au/australian-postgraduate-awards). JPM and JMM were awarded Senior Research Fellowships from the Australian National and Medical Research Council (www.nhmrc.gov.au). This project was funded by an Australian Research Council (www. arc.gov.au) Discovery Project Grant (DP110104332) to JMM and LC

Mealiness detection in apples using time resolved reflectance spectroscopy

Mealiness is a textural attribute related to internal fruit disorder that is characterized by the combination of abnormal softness of the fruit and absence of free juiciness in the mouth when eaten by the consumer. Time-resolved laser reflectance spectroscopy was used as a tool to determine mealiness. This new technique in agrofood research may provide physical and chemical information independently and simultaneously, which is relevant to characterize mealiness. Using visible and near infrared lasers as light sources, time-resolved laser reflectance spectroscopy was applied to Golden Delicious and Cox apples (n = 90), to characterize batches of untreated samples and samples that were stored under conditions that promote the development of mealiness (20C & 95% RH). The collected database was clustered into different groups according to their instrumental test values. The optical coefficients were used as explanatory variables to build discriminant functions for mealiness. The performance of the classification models created ranged from 47 to 100% of correctly identified mealy versus nonmealy apples

The intra-generational redistributive effects of social security

This paper provides a quantitative evaluation of the intra--cohort redistributive elements of the United States social security system in the context of a computable general equilibrium model. I determine how the well--being of individuals that differ across {\sl gender, race} and {\sl education} is affected by government social security policy. I find that females, whites and non--college graduates stand less to gain (lose) from reductions (increases) in the size of social security than males, non--whites and college graduates, respectively. Differences in mortality risk and labor productivity translate into differences in the magnitudes of capital accumulation and labor supply distortions, that are responsible for the observed welfare difference between types. Results imply that the current program is lifetime progressive across gender and education, yet lifetime regressive across race.Social security, demographics, heterogeneity, redistribution, simulation

Sponges architecture by colour: new insights into the fibres morphogenesis, skeletal spatial layout and morpho-anatomical traits of a marine horny sponge species (Porifera)

This paper focuses on the skeletal architecture and morphotraits of the Mediterranean horny sponge Sarcotragus spinosulus (Demospongiae, Keratosa, Dictyoceratida, Irciniidae). This special endoskeletal system consists of a dense, variably complex connective architecture, which extends throughout the entire sponge body and is embedded in an abundant jelly-like extracellular matrix (ECM). To investigate the topographic arrangement and micro-morphotraits of these connective structures in detail and by colour, also during morphogenetic processes, histology techniques using light microscopy are essential. New information is provided on the coordinated morphogenetic processes that characterize the growth and assembly of collagenic prototype structures in the matrix of fibrous skeletal elements and drive skeleton remodelling. Our results also highlight some novelties and some remarkable peculiarities of fibrous, filamentous and fibrillar components at the levels of both composition and structure. The morphofunctional significance of skeletal architecture is suggested in the background of the anatomical complexity of S. spinosulus

Functional Near Infrared Spectroscopy and Diffuse Optical Tomography in Neuroscience

Diseases & disorder

Assessment of low-dose cisplatin as a model of nausea and emesis in beagle dogs, potential for repeated administration

Cisplatin is a highly emetogenic cancer chemotherapy agent, which is often used to induce nausea and emesis in animal models. The cytotoxic properties of cisplatin also cause adverse events that negatively impact on animal welfare preventing repeated administration of cisplatin. In this study, we assessed whether a low (subclinical) dose of cisplatin could be utilized as a model of nausea and emesis in the dog while decreasing the severity of adverse events to allow repeated administration. The emetic, nausea-like behavior and potential biomarker response to both the clinical dose (70 mg/m2) and low dose (15 mg/m2) of cisplatin was assessed. Plasma creatinine concentrations and granulocyte counts were used to assess adverse effects on the kidneys and bone marrow, respectively. Nausea-like behavior and emesis was induced by both doses of cisplatin, but the latency to onset was greater in the low-dose group. No significant change in plasma creatinine was detected for either dose groups. Granulocytes were significantly reduced compared with baseline (P = 0.000) following the clinical, but not the low-dose cisplatin group. Tolerability of repeated administration was assessed with 4 administrations of an 18 mg/m2 dose cisplatin. Plasma creatinine did not change significantly. Cumulative effects on the granulocytes occurred, they were significantly decreased (P = 0.03) from baseline at 3 weeks following cisplatin for the 4th administration only. Our results suggest that subclinical doses (15 and 18 mg/m2) of cisplatin induce nausea-like behavior and emesis but have reduced adverse effects compared with the clinical dose allowing for repeated administration in crossover studies

A first immunohistochemistry study of transketolase and transketolase-like 1 expression in canine hyperplastic and neoplastic mammary lesions

Background: Canine mammary tumors represent the most common neoplasm in female dogs, and the discovery of cancer biomarkers and their translation to clinical relevant assays is a key requirement in the war on cancer. Since the description of the 'Warburg effect', the reprogramming of metabolic pathways is considered a hallmark of pathological changes in cancer cells. In this study, we investigate the expression of two cancer-related metabolic enzymes, transketolase (TKT) and transketolase-like 1 (TKTL1), involved in the pentose phosphate pathway (PPP), an alternative metabolic pathway for glucose breakdown that could promote cancer by providing the precursors and energy required for rapidly growing cells. Results: TKT and TKTL1 protein expression was investigated by immunohistochemistry in canine normal (N = 6) and hyperplastic glands (N = 3), as well as in benign (N = 11) and malignant mammary tumors (N = 17). TKT expression was higher in hyperplastic lesions and in both benign and malignant tumors compared to the normal mammary gland, while TKTL1 levels were remarkably higher in hyperplastic lesions, simple adenomas and simple carcinomas than in the normal mammary glands (P < 0.05). Conclusions: This study reveals that the expression of a key PPP enzyme varies along the evolution of canine mammary neoplastic lesions, and supports a role of metabolic changes in the development of canine mammary tumors

Accuracy in mineral identification: image spectral and spatial resolutions and mineral spectral properties

Problems related to airborne hyperspectral image data are reviewed and the requirements for data analysis applied to mineralogical (rocks and soils) interpretation are discussed. The variability of mineral spectral features, including absorption position, shape and depth is considered and interpreted as due to chemical composition, grain size effects and mineral association. It is also shown how this variability can be related to well defined geologic processes. The influence of sensor noise and diffuse atmospheric radiance in classification accuracy is also analyzed

Generation, characterization, and medical utilization of laser-produced emission continua

Intense continua of electromagnetic radiation of very brief duration are formed in the interaction of focused ultra-short terawatt laser pulses with matter. Two different kinds of experiments, which have been performed utilizing the Lund 10 Hz titanium-doped sapphire terawatt laser system are being described, where visible radiation and X-rays, respectively, have been generated. Focusing into water leads to the generation of a light continuum through self-phase modulation. The propagation of the light through tissue was studied addressing questions related to optical mammography and specific chromophore absorption. When terawatt laser pulses are focused onto a solid target with high nuclear charge Z, intense X-ray radiation of few ps duration and with energies exceeding hundreds of keV is emitted. Biomedical applications of this radiation are described, including differential absorption and gated-viewing imaging

Hemodynamic and EEG Time-Courses During Unilateral Hand Movement in Patients with Cortical Myoclonus. An EEG-fMRI and EEG-TD-fNIRS Study.

Multimodal human brain mapping has been proposed as an integrated approach capable of improving the recognition of the cortical correlates of specific neurological functions. We used simultaneous EEG-fMRI (functional magnetic resonance imaging) and EEG-TD-fNIRS (time domain functional near-infrared spectroscopy) recordings to compare different hemodynamic methods with changes in EEG in ten patients with progressive myoclonic epilepsy and 12 healthy controls. We evaluated O(2)Hb, HHb and Blood oxygen level-dependent (BOLD) changes and event-related desynchronization/synchronization (ERD/ERS) in the alpha and beta bands of all of the subjects while they performed a simple motor task. The general linear model was used to obtain comparable fMRI and TD-fNIRS activation maps. We also analyzed cortical thickness in order to evaluate any structural changes. In the patients, the TD-NIRS and fMRI data significantly correlated and showed a significant lessening of the increase in O(2)Hb and the decrease in BOLD. The post-movement beta rebound was minimal or absent in patients. Cortical thickness was moderately reduced in the motor area of the patients and correlated with the reduction in the hemodynamic signals. The fMRI and TD-NIRS results were consistent, significantly correlated and showed smaller hemodynamic changes in the patients. This finding may be partially attributable to mild cortical thickening. However, cortical hyperexcitability, which is known to generate myoclonic jerks and probably accounts for the lack of EEG beta-ERS, did not reflect any increased energy requirement. We hypothesize that this is due to a loss of inhibitory neuronal components that typically fire at high frequencies