DACH1 regulates macrophage activation and tumour progression in hypopharyngeal squamous cell carcinoma.

Dachshund family transcription factor 1 (DACH1) has been shown to exhibit a tumour-suppressive role in a number of human cancers. However, the role of DACH1 in hypopharyngeal squamous cell carcinoma (HPSCC) and its function in the tumour microenvironment (TME) are still not clear. Crosstalk between cancer cells and tumour-associated macrophages (TAMs) mediates tumour progression in HPSCC. The expression of DACH1, CD86 and CD163 was detected in 71 matched HPSCC-non-cancerous tissue pairs using quantitative real-time polymerase chain reaction and IHC analysis. Cell proliferation, migration and invasion were monitored by colony formation, Transwell and EdU incorporation assays. ChIP-qPCR and dual-luciferase reporter assays were applied to verify the targeting relationships between DACH1 and IGF-1. Stably transfected HPSCC cells were co-cultured with MΦ macrophages to assess macrophage polarization and secretory signals. DACH1 was decreased in HPSCC tissues and was indicative of a poor prognosis for HPSCC patients. Decreased DACH1 expression in HPSCC was associated with fewer CD86+ TAMs and more CD163+ TAMs. Knockdown of DACH1 inhibited the proliferation, migration and invasion of FaDu cells via Akt/NF-κB/MMP2/9 signalling. Additionally, DACH1 was found to directly bind to the promoter region of IGF-1 to downregulate the secretion of IGF-1, which inhibited TAMs polarization through the IGF-1R/JAK1/STAT3 axis. Furthermore, in nude mice, the effects of DACH1 inhibition on tumour progression and M2-like TAMs polarization were confirmed. These findings suggest that IGF-1 is a critical downstream effector of DACH1 that suppresses cell migration and invasion and inhibits TAMs polarization. DACH1 could be a therapeutic target and prognostic marker for HPSCC.

Processing of sting pheromone and its components in the antennal lobe of the worker honeybee.

In the honeybee Apis mellifera, a sting pheromone produced by sting glands plays an important role in coordinating defensive behavior. This pheromone is a blend constituted by several components. Little is known about the neural substrates underlying sting pheromone processing in the bee brain. Here, we investigated the neural activity elicited by eight components (five acetates and three alcohols) of the sting pheromone, and by real bee stings at the level of the antennal lobe (AL) of worker honeybees. We used in vivo calcium imaging to record odor-induced neural activity of 22 identified glomeruli in the AL. We found that acetates mainly activated medial glomeruli while alcohols mainly activated lateral dorsal glomeruli. The sting preparation evoked a glomerular pattern that was clearly distinct from those of individual pheromone components. No particular region of the imaged AL was found to process sting pheromone or any of its components. Further analyses in a putative honeybee olfactory space showed that the neural activity elicited by sting preparation cannot be linearly predicted by those of pheromone components and that such components are not clearly separated from non-sting pheromone odors. We conclude that sting pheromone is processed in the worker honeybee AL following the same principles of general odors so that the chemical structure of odorants is the main determinant of glomerular activation, rather than their pheromonal values. We cannot exclude, however, that the distinctness of sting-pheromone representation with respect to that of its components constitutes a form of specialized neural processing strategy for this kind of substance.

Maturation of odor representation in the honeybee antennal lobe.

The antennal lobe (AL) is the first center for processing odors in the insect brain, as is the olfactory bulb (OB) in vertebrates. Both the AL and the OB have a characteristic glomerular structure; odors sensed by olfactory receptor neurons are represented by patterns of glomerular activity. Little is known about when and how an odor begins to be perceived in a developing brain. We address this question by using calcium imaging to monitor odor-evoked neural activity in the ALs of bees of different ages. We find that odor-evoked neural activity already occurs in the ALs of bees as young as 1 or 2 days. In young bees, the responses to odors are relatively weak and restricted to a small number of glomeruli. However, different odors already evoke responses in different combinations of glomeruli. In mature bees, the responses are stronger and are evident in more glomeruli, but continue to have distinct odor-dependent signatures. Our findings indicate that the specific glomerular patterns for odors are conserved during the development, and that odor representations are fully developed in the AL during the first 2 weeks following emergence.

Behavioral modification in choice process ofDrosophila.

In visual operant conditioning ofDrosophila at the flight simulator, only motor output of flies-yaw torque-is recorded, which is involved in the conditioning process. The current study used a newly-designed data analysis method to study the torque distribution ofDrosophila. Modification of torque distribution represents the effects of operant conditioning on flies' behavioral mode. Earlier works([10]) showed that, when facing contradictory visual cues, flies could make choices based upon the relative weightiness of different cues, and it was demonstrated that mushroom bodies might play an important role in such choice behavior. The new "torque-position map" method was used to explore the CS-US associative learning and choice behavior inDrosophila from the aspect of its behavioral mode. Finally, this work also discussed various possible neural bases involved in visual associative learning, choice processing and modification processing of the behavioral mode in the visual operant conditioning ofDrosophila.

Function of attention in learning process in the olfactory bulb.

It has been suggested that in the olfactory bulb, odor information is processed through parallel channels and learning depends on the cognitive environment. The synapse's spike effective time is defined as the effective time for a spike from pre-synapse to post-synapse, which varies with the type of synapse. A learning model of the olfactory bulb was constructed for synapses with varying spike effective times. The simulation results showed that such a model can realize the multi-channel processing of information in the bulb. Furthermore, the effect of the cognitive environment on the learning process was also studied. Different feedback frequencies were used to express different attention states. Considering the information's multi-channel processing requirement for learning, a learning rule considering both spike timing and average spike frequency is proposed. Simulation results showed that habituation and anti-habituation of an odor in the olfactory bulb might be the result of learning guided by a common local learning rule but at different attention states.

Dissociation of visual associative and motor learning in Drosophila at the flight simulator.

Ever since operant conditioning was studied experimentally, the relationship between associative learning and possible motor learning has become controversial. Although motor learning and its underlying neural substrates have been extensively studied in mammals, it is still poorly understood in invertebrates. The visual discriminative avoidance paradigm of Drosophila at the flight simulator has been widely used to study the flies' visual associative learning and related functions, but it has not been used to study the motor learning process. In this study, newly-designed data analysis was employed to examine the flies' solitary behavioural variable that was recorded at the flight simulator-yaw torque. Analysis was conducted to explore torque distributions of both wild-type and mutant flies in conditioning, with the following results: (1) Wild-type Canton-S flies had motor learning performance in conditioning, which was proved by modifications of the animal's behavioural mode in conditioning. (2) Repetition of training improved the motor learning performance of wild-type Canton-S flies. (3) Although mutant dunce(1) flies were defective in visual associative learning, they showed essentially normal motor learning performance in terms of yaw torque distribution in conditioning. Finally, we tentatively proposed that both visual associative learning and motor learning were involved in the visual operant conditioning of Drosophila at the flight simulator, that the two learning forms could be dissociated and they might have different neural bases.