Lloydcormier4194

Trastuzumab emtansine (T-DM1), an antibody-drug conjugate (ADC) of trastuzumab and cytotoxic agent emtansine (DM1), has been approved for the therapy of metastatic HER2-positive breast cancer after prior treatment of trastuzumab and taxane. The impressive efficacy exhibited by T-DM1 has heightened the need for more further studies on the underlying mechanisms of T-DM1 cytotoxicity. Previous research suggested that autophagy was crucial for cancer therapy, but the role of autophagy in T-DM1 treatment has not been investigated. Here, we demonstrated for the first time that T-DM1 triggered obvious autophagy in HER2-positive SK-BR-3 and BT-474 breast cancer cells. Blocking autophagy with pharmacological inhibitors chloroquine (CQ) or LY294002 partly reduced T-DM1-induced apoptosis and Caspase-3/7 activation, suggesting that autophagy played an essential role in the cytotoxicity induced by T-DM1 in HER2-positive breast cancer cells. Further investigation demonstrated that Akt/mTOR signaling pathway was involved in T-DM1-induced autophagy in a time-dependent manner. Altogether, our results highlighted the important role of autophagy as a novel mechanism for T-DM1-induced cytotoxicity and elucidated the critical relationships between T-DM1-induced autophagy and apoptosis in human HER2-positive breast cancer cells, which provides novel insight into the underlying anti-tumor mechanism of T-DM1.To determine how males of the large carpenter bee, Xylocopa appendiculata, maximize access to females while minimizing energy cost and acquiring energy for territorial flights, we investigated the times of territorial flights by males and foraging by males and females. Males were present continuously in territories from 800 to 1200. They approached, chased, and excluded conspecific males from their territories. In the laboratory, males showed higher locomotor and flight activities in the morning and lower activities in the afternoon. Both males and females visited flowers from 800 to 1600, but the most frequent visits were earlier in females (1000-1200) than in males (1200-1300). Relative body weights in territorial males often increased. selleck chemicals These results indicate that the males time their territorial flights to maximize contact with females and obtain nectar as fuel between and after the territorial flights. The time-related territorial flight in males might be based on a time-keeping system in the brain. Brain levels of serotonin and its precursor tryptophan were significantly higher in males collected at 1600 than at 1100, suggesting a relation between time-related territorial flight and serotonin synthesis in the brain.Decades of research have provided evidence that object representations contribute to attentional selection. However, most evidence for object-based attentional allocation is drawn from studies employing the two-rectangle paradigm where the target distribution is biased towards the cued object. It is thus unclear whether object-based attentional selection is from object representations or a consequence of spatial attention based on statistical imbalances. Here, we investigate the extent to which target frequency modulates object-based attention by systematically manipulating the frequency of target appearance in a particular spatial location within objects to equate spatial allocation, bias specific spatial locations, or bias objects. In four experiments, participants were presented with a variant of the two-rectangle paradigm in which one end of a rectangle was cued and performed a target discrimination task. Critically, the target location probabilities were parametrically manipulated. The target could appear equally in all ends within the objects (valid, invalid within-object, invalid between-object, diagonal) (Experiment 1) or with overall equality between objects but biased towards the invalid locations (Experiment 2). The target could also appear in three locations (valid, invalid within-object, invalid between-object) distributed equally between objects but biased towards the invalid between-object location (Experiment 3) or with an overall bias towards the invalid between-object location (Experiment 4). We observed that while objects bias attention, spatial biases are prioritized over object representations. Combined results suggest that object-based contribution to attentional guidance is the result of both spatial probabilities and object representations.This study provides clear evidence that the human cognitive system automatically codes sound pitch spatially. The spatial-musical association of response codes (SMARC) effect, in which a high-pitched (low-pitched) tone facilitates an upper (lower) response, is considered to reflect the spatial coding of sound pitch. However, previous studies have not excluded the directional effects of sound localization. Because a high-pitched (low-pitched) tone is automatically misperceived as originating from a spatially high (low) location, the location of a perceived sound source might artificially elicit the SMARC effect. This study challenged this unresolved issue. Participants were trained to associate visual stimuli (novel contoured shapes) with sound pitches (high-pitched or low-pitched pure tones). After training, participants completed a discrimination task in which the vertically aligned keys were associated with the visual stimuli in the absence of sound. Even without sound, the SMARC effect was observed in response to the trained visual stimuli (Experiment 1). However, this sound-free SMARC effect was eliminated when training was omitted (Experiment 2). Therefore, the SMARC effect was observed based solely on the activation of sound imagery that was spatial.The current study investigates the role of temporal processing in the visual domain in participants with developmental dyslexia (DD), the most common neurodevelopmental disorder, which is characterized by severe and specific difficulties in learning to read despite normal intelligence and adequate education. Specifically, our aim was to test whether DD is associated with a general impairment of temporal sensory processing or a specific deficit in temporal integration (which ensures stability of object identity and location) or segregation (which ensures sensitivity to changes in visual input). Participants with DD performed a task that measured both temporal integration and segregation using an identical sequence of two displays separated by a varying interstimulus interval (ISI) under two different task instructions. Results showed that participants with DD performed worse in the segregation task, with a shallower slope of the psychometric curve of percentage correct as a function of the ISI between the two target displays.