Innate immune and proinflammatory signals activate the Hippo pathway via a Tak1-STRIPAK-Tao axis.

The Hippo pathway controls developmental, homeostatic and regenerative tissue growth, and is frequently dysregulated in various diseases. Although this pathway can be activated by innate immune/inflammatory stimuli, the underlying mechanism is not fully understood. Here, we identify a conserved signaling cascade that leads to Hippo pathway activation by innate immune/inflammatory signals. We show that Tak1, a key kinase in innate immune/inflammatory signaling, activates the Hippo pathway by inducing the lysosomal degradation of Cka, an essential subunit of the STRIPAK PP2A complex that suppresses Hippo signaling. Suppression of STRIPAK results in the activation of Hippo pathway through Tao-Hpo signaling. We further show that Tak1-mediated Hippo signaling is involved in processes ranging from cell death to phagocytosis and innate immune memory. Our findings thus reveal a molecular connection between innate immune/inflammatory signaling and the evolutionally conserved Hippo pathway, thus contributing to our understanding of infectious, inflammatory and malignant diseases.

Dried lemon slices improve bowel cleansing quality of polyethylene glycol for colonoscopy preparation: randomized controlled trial.

BACKGROUND: adequate bowel preparation is related to the quality of colonoscopy. Dried lemon slices can increase gastrointestinal peristalsis, which has shown potential as an adjuvant of bowel preparation. We hypothesized that the combination of dried lemon slices and polyethylene glycol (PEG) could improve the efficacy of bowel preparation and be more acceptable to participants. AIM: to investigate the effectiveness of lemon slices combined with PEG for colonoscopy preparation. METHODS: a prospective, single-center, randomized, controlled trial was performed of 521 patients randomly assigned to two groups. A total of 254 patients were given lemon slices based on conventional 4-L PEG treatment for the bowel, while 267 patients received only 4-L PEG treatment. Patients' basic information, procedure-related parameters, adverse effects, and subjective feelings were collected by questionnaires. Intestinal tract cleanliness was scored according to the Boston Bowel Preparation Scale (BBPS) by experienced endoscopists. Data were analyzed by the two-sample t-test or the Chi-squared test. RESULTS: the BBPS scores were significantly higher in the PEG + lemon slice group (p < 0.05). The taste acceptability, satisfaction, and willingness to repeat bowel preparation were significantly higher in the PEG+ lemon slice group (p < 0.05). However, a larger proportion of patients from the PEG+ lemon slice group (30.7 %) suffered abdominal distension compared with the PEG group (20.6 %), while the incidence of other adverse effects was comparable between the two groups. CONCLUSION: the addition of dried lemon slices to conventional PEG showed its superiority for bowel preparation.

Dried lemon slices improve bowel cleansing quality of polyethylene glycol for colonoscopy preparation: randomized controlled trial

Background: adequate bowel preparation is related to the quality of colonoscopy. Dried lemon slices can increase gastrointestinal peristalsis, which has shown potential as an adjuvant of bowel preparation. We hypothesized that the combination of dried lemon slices and polyethylene glycol (PEG) could improve the efficacy of bowel preparation and be more acceptable to participants. Aim: to investigate the effectiveness of lemon slices combined with PEG for colonoscopy preparation. Methods: a prospective, single-center, randomized, controlled trial was performed of 521 patients randomly assigned to two groups. A total of 254 patients were given lemon slices based on conventional 4-L PEG treatment for the bowel, while 267 patients received only 4-L PEG treatment. Patients’ basic information, procedure-related parameters, adverse effects, and subjective feelings were collected by questionnaires. Intestinal tract cleanliness was scored according to the Boston Bowel Preparation Scale (BBPS) by experienced endoscopists. Data were analyzed by the two-sample t-test or the Chi-squared test. Results: the BBPS scores were significantly higher in the PEG + lemon slice group (p < 0.05). The taste acceptability, satisfaction, and willingness to repeat bowel preparation were significantly higher in the PEG+ lemon slice group (p < 0.05). However, a larger proportion of patients from the PEG+ lemon slice group (30.7 %) suffered abdominal distension compared with the PEG group (20.6 %), while the incidence of other adverse effects was comparable between the two groups. Conclusion: the addition of dried lemon slices to conventional PEG showed its superiority for bowel preparation (AU)

Binding of guide piRNA triggers methylation of the unstructured N-terminal region of Aub leading to assembly of the piRNA amplification complex.

PIWI proteins use guide piRNAs to repress selfish genomic elements, protecting the genomic integrity of gametes and ensuring the fertility of animal species. Efficient transposon repression depends on amplification of piRNA guides in the ping-pong cycle, which in Drosophila entails tight cooperation between two PIWI proteins, Aub and Ago3. Here we show that post-translational modification, symmetric dimethylarginine (sDMA), of Aub is essential for piRNA biogenesis, transposon silencing and fertility. Methylation is triggered by loading of a piRNA guide into Aub, which exposes its unstructured N-terminal region to the PRMT5 methylosome complex. Thus, sDMA modification is a signal that Aub is loaded with piRNA guide. Amplification of piRNA in the ping-pong cycle requires assembly of a tertiary complex scaffolded by Krimper, which simultaneously binds the N-terminal regions of Aub and Ago3. To promote generation of new piRNA, Krimper uses its two Tudor domains to bind Aub and Ago3 in opposite modification and piRNA-loading states. Our results reveal that post-translational modifications in unstructured regions of PIWI proteins and their binding by Tudor domains that are capable of discriminating between modification states is essential for piRNA biogenesis and silencing.

piRNA Biogenesis in Drosophila melanogaster.

The PIWI-interacting RNA (piRNA) pathway is a conserved defense system that protects the genome integrity of the animal germline from deleterious transposable elements. Targets of silencing are recognized by small noncoding piRNAs that are processed from long precursor molecules. Although piRNAs and other classes of small noncoding RNAs, such as miRNAs and small interfering (si)RNAs, interact with members of the same family of Argonaute (Ago) proteins and their function in target repression is similar, the biogenesis of piRNAs differs from those of the other two small RNAs. Recently, many aspects of piRNA biogenesis have been revealed in Drosophila melanogaster. In this review, we elaborate on piRNA biogenesis in Drosophila somatic and germline cells. We focus on the mechanisms by which piRNA precursor transcription is regulated and highlight recent work that has advanced our understanding of piRNA precursor processing to mature piRNAs. We finish by discussing current models to the still unresolved question of how piRNA precursors are selected and channeled into the processing machinery.