Gaze-grasp coordination in obstacle avoidance: differences between binocular and monocular viewing

Most adults can skillfully avoid potential obstacles when acting in everyday cluttered scenes. We examined how gaze and hand movements are normally coordinated for obstacle avoidance and whether these are altered when binocular depth information is unavailable. Visual fixations and hand movement kinematics were simultaneously recorded, while 13 right-handed subjects reached-to-precision grasp a cylindrical household object presented alone or with a potential obstacle (wine glass) located to its left (thumb's grasp side), right or just behind it (both closer to the finger's grasp side) using binocular or monocular vision. Gaze and hand movement strategies differed significantly by view and obstacle location. With binocular vision, initial fixations were near the target's centre of mass (COM) around the time of hand movement onset, but usually shifted to end just above the thumb's grasp site at initial object contact, this mainly being made by the thumb, consistent with selecting this digit for guiding the grasp. This strategy was associated with faster binocular hand movements and improved end-point grip precision across all trials than with monocular viewing, during which subjects usually continued to fixate the target closer to its COM despite a similar prevalence of thumb-first contacts. While subjects looked directly at the obstacle at each location on a minority of trials and their overall fixations on the target were somewhat biased towards the grasp side nearest to it, these gaze behaviours were particularly marked on monocular vision-obstacle behind trials which also commonly ended in finger-first contact. Subjects avoided colliding with the wine glass under both views when on the right (finger side) of the workspace by producing slower and straighter reaches, with this and the behind obstacle location also resulting in 'safer' (i.e. narrower) peak grip apertures and longer deceleration times than when the goal object was alone or the obstacle was on its thumb side. But monocular reach paths were more variable and deceleration times were selectively prolonged on finger-side and behind obstacle trials, with this latter condition further resulting in selectively increased grip closure times and corrections. Binocular vision thus provided added advantages for collision avoidance, known to require intact dorsal cortical stream processing mechanisms, particularly when the target of the grasp and potential obstacle to it were fairly closely separated in depth. Different accounts of the altered monocular gaze behaviour converged on the conclusion that additional perceptual and/or attentional resources are likely engaged compared to when continuous binocular depth information is available. Implications for people lacking binocular stereopsis are briefly considered

Cisplatin-DNA adduct formation in patients treated with cisplatin-based chemoradiation: lack of correlation between normal tissues and primary tumor

Contains fulltext : 69595.pdf (publisher's version ) (Closed access)PURPOSE: In this study, the formation of cisplatin-DNA adducts after concurrent cisplatin-radiation and the relationship between adduct-formation in primary tumor tissue and normal tissue were investigated. METHODS: Three intravenous cisplatin-regimens, given concurrently with radiation, were studied: daily low-dose (6 mg/m(2)) cisplatin, weekly 40 mg/m(2), three-weekly 100 mg/m(2). A (32)P-postlabeling technique was used to quantify adducts in normal tissue [white blood cells (WBC) and buccal cells] and tumor. RESULTS: Normal tissue samples for adduct determination were obtained from 63 patients and tumor biopsies from 23 of these patients. Linear relationships and high correlations were observed between the levels of two guanosine- and adenosine-guanosine-adducts in normal and tumor tissue. Adduct levels in tumors were two to five times higher than those in WBC (P<0.001). No significant correlations were found between adduct levels in normal tissues and primary tumor biopsies, nor between WBC and buccal cells. CONCLUSIONS: In concurrent chemoradiotherapy schedules, cisplatin adduct levels in tumors were significantly higher than in normal tissues (WBC). No evidence of a correlation was found between adduct levels in normal tissues and primary tumor biopsies. This lack of correlation may, to some extent, explain the inconsistencies in the literature regarding whether or not cisplatin-DNA adducts can be used as a predictive test in anticancer platinum therapy

Characterization of an extracellular lipase and its chaperone from Ralstonia eutropha H16

Lipase enzymes catalyze the reversible hydrolysis of triacylglycerol to fatty acids and glycerol at the lipid–water interface. The metabolically versatile Ralstonia eutropha strain H16 is capable of utilizing various molecules containing long carbon chains such as plant oil, organic acids, or Tween as its sole carbon source for growth. Global gene expression analysis revealed an upregulation of two putative lipase genes during growth on trioleate. Through analysis of growth and activity using strains with gene deletions and complementations, the extracellular lipase (encoded by the lipA gene, locus tag H16_A1322) and lipase-specific chaperone (encoded by the lipB gene, locus tag H16_A1323) produced by R. eutropha H16 was identified. Increase in gene dosage of lipA not only resulted in an increase of the extracellular lipase activity, but also reduced the lag phase during growth on palm oil. LipA is a non-specific lipase that can completely hydrolyze triacylglycerol into its corresponding free fatty acids and glycerol. Although LipA is active over a temperature range from 10 °C to 70 °C, it exhibited optimal activity at 50 °C. While R. eutropha H16 prefers a growth pH of 6.8, its extracellular lipase LipA is most active between pH 7 and 8. Cofactors are not required for lipase activity; however, EDTA and EGTA inhibited LipA activity by 83 %. Metal ions Mg[superscript 2+], Ca[superscript 2+], and Mn[superscript 2+] were found to stimulate LipA activity and relieve chelator inhibition. Certain detergents are found to improve solubility of the lipid substrate or increase lipase-lipid aggregation, as a result SDS and Triton X-100 were able to increase lipase activity by 20 % to 500 %. R. eutropha extracellular LipA activity can be hyper-increased, making the overexpression strain a potential candidate for commercial lipase production or in fermentations using plant oils as the sole carbon source.Malaysia-MIT Biotechnology Partnership Programm

Quantitative analysis of HER family proteins using mass spectrometry as a predictive tool of response to anti-HER therapies in breast cancer

Premi Extraordinari de Doctorat concedit pels programes de doctorat de la UAB per curs acadèmic 2017-2018Introducción: La expresión desregulada y la actividad de los miembros de la familia HER es frecuente en el cáncer de mama (CM). Hasta el 25% de CM sobreexpresan HER2. Los altos niveles de este oncogén, casi invariablemente como consecuencia de la amplificación genómica, conllevan una enfermedad agresiva y es una importante diana terapéutica. Los anticuerpos monoclonales y las pequeñas moléculas inhibidoras de quinasa son las principales estrategias dirigidas contra HER2 en CM. Aunque el tratamiento con trastuzumab se asocia con importantes beneficios en términos de supervivencia, un número significativo de pacientes con CM HER2-positivo no se benefician de ella o se vuelven resistentes. Otros fármacos anti-HER2 (por ejemplo, lapatinib, pertuzumab y T-DM1) han sido aprobados para el tratamiento de CM metastásico HER2-positivo después de la progresión a trastuzumab. Estos nuevos fármacos anti-HER2 están siendo probados en el tratamiento adyuvante, solo o en regímenes de anticuerpos duales sin quimioterapia concomitante o secuencial. Identificar qué pacientes con CM tienen más probabilidades de beneficiarse de una u otra forma de terapia dirigida anti-HER es crucial. Los métodos actuales para la determinación del estado de HER2 (IHC y FISH) son semicuantitativos, sufren de problemas de reproducibilidad, y no predicen la respuesta al trastuzumab. El objetivo principal de este proyecto fue investigar si el análisis cuantitativo de la proteína HER2 por espectrometría de masas (MS) puede mejorar la predicción actual de respuesta o resistencia a los medicamentos dirigidos contra HER. Métodos: Hemos cuantificado mediante MS los niveles de proteína HER2 en muestras de tejido, fijados en formol e incluidos en parafina que habían sido clasificadas como negativas (HER2 0, 1+), equívoca (2+) o positiva (3+) por inmunohistoquímica (IHC). Las curvas ROC (Característica Operativa del Receptor) se construyeron mediante el cálculo de la sensibilidad y especificidad de cantidades crecientes de HER2 (por MS) en la predicción de positividad de HER2 (por IHC/ISH combinado) y de beneficio en la supervivencia después de tratamiento con anti-HER2. El análisis de supervivencia se llevo a cabo con el método de Kaplan-Meier y las curvas se compararon mediante el test del Log-Rank. Para el análisis multivariable se utilizó la regresión de Cox ajustado por el estado de los receptores hormonales, el estadío del tumor, los ganglios linfáticos y los niveles de HER2 por MS. Los resultados se consideraron significativos cuando los valores de p (p) fueron menos de 0,05. Resultados: Los niveles absolutos de HER2 (amol/μg) se correlacionaron significativamente con HER2 por IHC y el estado de la amplificación por ISH (p 0,0001). Dentro de la categoría de IHC-positivos (3+), se observó un amplio rango dinámico de la expresión de la proteína HER2 (de 163,7 a 17,446.7 amol/μg). Utilizando el punto de corte de 740 amol/μg, la tasa de correlación entre HER2 por MS y estándar IHC/ISH fue del 94% (p 2200 mg amol/μg obtienen un beneficio más grande tras el tratamiento con la terapia anti-HER2 que los pacientes con bajos niveles de expresión de HER2

SITE-DIRECTED MUTAGENESIS AND X-RAY CRYSTALLOGRAPHY OF 2 PHOSPHOLIPASE-A2 MUTANTS - Y52F AND Y73F

Tyr52 and Tyr73 are conserved amino acid residues throughout all vertebrate phospholipases A2. They are part of an extended hydrogen bonding system that links the N-terminal alpha-NH+-group to the catalytic residues His48 and Asp99. These tyrosines were replaced by phenylalanines in a porcine pancreatic phospholipase A2 mutant, in which residues 62 - 66 had been deleted (DELTA62 - 66PLA2). The mutations did not affect the catalytic properties of the enzyme, nor the folding kinetics. The stability against denaturation by guanidine hydrochloride was decreased, however. To analyse how the enzyme compensates for the loss of the tyrosine hydroxyl group, the X-ray structures of the DELTAY52F and DELTAY73F mutants were determined. After crystallographic refinement the final crystallographic R-factors were 18.1% for the DELTAY52F mutant (data between 7 and 2.3 angstrom resolution) and 19.1% for the DELTAY73F mutant (data between 7 and 2.4 angstrom resolution). No conformational changes occurred in the mutants compared with the DELTA62 - 66PLA2, but an empty cavity formed at the site of the hydroxyl group of the former tyrosine. In both mutants the Asp99 side chain loses one of its hydrogen bonds and this might explain the observed destabilization