Neurophysiological basis of stress-induced aversive memory in the nematode Caenorhabditis elegans.

Physiological stress induces aversive memory formation and profoundly impacts animal behavior. In C. elegans, concurrent mitochondrial disruption induces aversion to the bacteria that the animal inherently prefers, offering an experimental paradigm for studying the neural basis of aversive memory. We find that, under mitochondrial stress, octopamine secreted from the RIC modulatory neuron targets the AIY interneuron through the SER-6 receptor to trigger learned bacterial aversion. RIC responds to systemic mitochondrial stress by increasing octopamine synthesis and acts in the formation of aversive memory. AIY integrates sensory information, acts downstream of RIC, and is important for the retrieval of aversive memory. Systemic mitochondrial dysfunction induces RIC responses to bacterial cues that parallel stress induction, suggesting that physiological stress activates latent communication between RIC and the sensory neurons. These findings provide insights into the circuit and neuromodulatory mechanisms underlying stress-induced aversive memory.

Integrin molecular tension required for focal adhesion maturation and YAP nuclear translocation.

Focal adhesions (FAs) provide the cells linkages to extracellular matrix (ECM) at sites of integrins binding and transmit mechanical forces between the ECM and the actin cytoskeleton. Cells sense and respond to physical stimuli from their surrounding environment through the activation of mechanosensitive signaling pathways, a process called mechanotransduction. In this study, we used RGD-peptide conjugated DNA tension gauge tethers (TGTs) with different tension tolerance (Ttol) to determine the molecular forces required for FA maturation in different sizes and YAP nuclear translocation. We found that the limitation of FA sizes in cells seeded on TGTs with different Ttol were less than 1 µm, 2 µm, 3 µm, and 6 µm for Ttol values of 43 pN, 50 pN, 54 pN, and 56 pN, respectively. This suggests that the molecular tension across integrins increases gradually as FA size increases throughout FA maturation. For YAP nuclear translocation, significant YAP nuclear localization was observed only in the cells seeded on the TGTs with Ttol ≥ 54 pN, but not on TGTs with Ttol ≤ 50 pN, suggesting a threshold of molecular force across integrins for YAP nuclear translocation lies in the range of 50 pN-54 pN.

A role for dopamine in C. elegans avoidance behavior induced by mitochondrial stress.

Physiological stress triggers aversive learning that profoundly alters animal behavior. Systemic mitochondrial disruption induces avoidance of C. elegans to non-pathogenic food bacteria. Mutations in cat-2 and dat-1, which control dopamine synthesis and reuptake, respectively, impair this learned bacterial avoidance, suggesting that dopaminergic modulation is essential. Cell-specific rescue experiments indicate that dopamine likely acts from the CEP and ADE neurons to regulate learned bacterial avoidance. We find that mutations in multiple dopamine receptor genes, including dop-1, dop-2 and dop-3, reduced learned bacterial avoidance. Our work reveals a role for dopamine signaling in C. elegans learned avoidance behavior induced by mitochondrial stress.

Wnt signalling and endocytosis: Mechanisms, controversies and implications for stress responses.

Wnt signalling is one of a few conserved pathways that control diverse aspects of development and morphogenesis in all metazoan species. Endocytosis is a key mechanism that regulates the secretion and graded extracellular distribution of Wnt glycoproteins from the source cells, as well as Wnt signal transduction in the receiving cells. However, controversies exist regarding the requirement of clathrin-dependent endocytosis in Wnt signalling. Various lines of evidence from recent studies suggest that Wnt-ß-catenin signalling is also involved in the regulation of cellular stress responses in adulthood, a role that is beyond its canonical functions in animal development. In this review, we summarise recent advances in the molecular and cellular mechanisms by which endocytosis modulates Wnt signalling. We also discuss how Wnt signalling could be repurposed to regulate mitochondrial stress response in the nematode Caenorhabditis elegans.

Pulmonary Blastoma in Children: Report of a Rare Case and Review of the Literature.

Pulmonary blastoma is a rare malignant lung tumor with aggressive behavior and dismal prognosis. It is extremely rare in children aged <18 years, and little is known about its genetic alteration and pathogenesis. Although surgical resection and adjuvant chemotherapy or radiotherapy have been applied in several cases, no standard treatment guidelines with sufficient evidence have been established. In this article, we report a case of a large pulmonary blastoma in a 7-year-old girl whose initial presentation was progressive dyspnea and productive cough. We subsequently present a review on cases involving young patients as well as genetic analysis data available in the literature.