Unperceived, the impact of information gap design plateware on food waste.

Curiosity is a powerful motivator of behaviour. Although there have been some studies pertaining to the application of curiosity in the realm of food, research examining the potential to influence consumer food waste behaviour through the induction of curiosity is lacking. This study conducted two onsite dining experiments to explore the role and mechanism of curiosity in reducing food waste in a real dining environment by utilising an information gap design in tableware to induce participants' curiosity. Experiment 1 investigated the differences in food waste between participants using bowls with an information gap design and those using bowls with no information gap (blank bowls). Experiment 2 further controlled for other variables that could potentially influence the outcomes between bowls with and without information gaps; the latter displayed complete text externally. The results of both experiments consistently demonstrated a significant reduction in participants' food waste when utilising utensils with an information gap design. Moreover, we conducted an exploratory analysis combining these two experiments to examine the mediating mechanisms involved. Furthermore, the exploratory analysis suggested the mediating mechanism of curiosity elicited by the information gap design, ultimately leading to a decrease in food waste. This study presents a potential avenue for a simple and innovative approach for mitigating food waste.

Regulation of cardiac microRNAs by cardiac microRNAs.

RATIONALE: MicroRNAs modestly suppress their direct mRNA targets, and these direct effects are amplified by modulation of gene transcription pathways. Consequently, indirect mRNA modulatory effects of microRNAs to increase or decrease mRNAs greatly outnumber direct target suppressions. Because microRNAs are products of transcription, the potential exists for microRNAs that regulate transcription to regulate other microRNAs. OBJECTIVE: Determine whether cardiac-expressed microRNAs regulate expression of other cardiac microRNAs, and measure the impact of microRNA-mediated microRNA regulation on indirect regulation of nontarget mRNAs. METHODS AND RESULTS: Transgenic expression of pre-microRNAs was used to generate mouse hearts expressing 6- to 16-fold normal levels of microRNA (miR)-143, miR-378, and miR-499. Genome-wide mRNA and microRNA signatures were established using deep sequencing; expression profiles provoked by each microRNA were defined. miR-143 suppressed its direct cardiac mRNA target hexokinase 2, but exhibited little indirect target regulation and did not regulate other cardiac microRNAs. Both miR-378 and miR-499 indirectly regulated hundreds of cardiac mRNAs and 15 to 30 cardiac microRNAs. MicroRNA overexpression did not alter normal processing of either transgenic or endogenous cardiac microRNAs, and microRNA-mediated regulation of other microRNAs encoded within parent genes occurred in tandem with parent mRNAs. MicroRNA regulation by miR-378 and miR-499 was stimulus specific, and contributed to observed mRNA downregulation. CONCLUSIONS: MicroRNAs that modulate cardiac transcription can indirectly regulate other microRNAs. Transcriptional modulation by microRNAs, and microRNA-mediated microRNA regulation, help explain how small direct effects of microRNAs are amplified to generate striking phenotypes.

Epitranscriptional orchestration of genetic reprogramming is an emergent property of stress-regulated cardiac microRNAs.

Cardiac stress responses are driven by an evolutionarily conserved gene expression program comprising dozens of microRNAs and hundreds of mRNAs. Functionalities of different individual microRNAs are being studied, but the overall purpose of interactions between stress-regulated microRNAs and mRNAs and potentially distinct roles for microRNA-mediated epigenetic and conventional transcriptional genetic reprogramming of the stressed heart are unknown. Here we used deep sequencing to interrogate microRNA and mRNA regulation in pressure-overloaded mouse hearts, and performed a genome-wide examination of microRNA-mRNA interactions during early cardiac hypertrophy. Based on abundance and regulatory patterns, cardiac microRNAs were categorized as constitutively expressed housekeeping, regulated homeostatic, or dynamic early stress-responsive microRNAs. Regulation of 62 stress-responsive cardiac microRNAs directly affected levels of only 66 mRNAs, but the global impact of microRNA-mediated epigenetic regulation was amplified by preferential targeting of mRNAs encoding transcription factors, kinases, and phosphatases exerting amplified secondary effects. Thus, an emergent cooperative property of stress-regulated microRNAs is orchestration of transcriptional and posttranslational events that help determine the stress-reactive cardiac phenotype. This global functionality explains how large end-organ effects can be induced through modest individual changes in target mRNA and protein content by microRNAs that sense and respond dynamically to a changing physiological milieu.

Direct and indirect involvement of microRNA-499 in clinical and experimental cardiomyopathy.

RATIONALE: MicroRNA-499 and other members of the myomiR family regulate myosin isoforms in pressure-overload hypertrophy. miR-499 expression varies in human disease, but results of mouse cardiac miR-499 overexpression are inconsistent, either protecting against ischemic damage or aggravating cardiomyopathy after pressure overload. Likewise, there is disagreement over direct and indirect cardiac mRNAs targeted in vivo by miR-499. OBJECTIVE: To define the associations between regulated miR-499 level in clinical and experimental heart disease and modulation of its predicted mRNA targets and to determine the consequences of increased cardiac miR-499 on direct mRNA targeting, indirect mRNA modulation, and on myocardial protein content and posttranslational modification. METHODS AND RESULTS: miR-499 levels were increased in failing and hypertrophied human hearts and associated with decreased levels of predicted target mRNAs. Likewise, miR-499 is increased in Gq-mediated murine cardiomyopathy. Forced cardiomyocyte expression of miR-499 at levels comparable to human cardiomyopathy induced progressive murine heart failure and exacerbated cardiac remodeling after pressure overloading. Genome-wide RNA-induced silencing complex and RNA sequencing identified 67 direct, and numerous indirect, cardiac mRNA targets, including Akt and MAPKs. Myocardial proteomics identified alterations in protein phosphorylation linked to the miR-499 cardiomyopathy phenotype, including of heat shock protein 90 and protein serine/threonine phosphatase 1-α. CONCLUSIONS: miR-499 is increased in human and murine cardiac hypertrophy and cardiomyopathy, is sufficient to cause murine heart failure, and accelerates maladaptation to pressure overloading. The deleterious effects of miR-499 reflect the cumulative consequences of direct and indirect mRNA regulation, modulation of cardiac kinase and phosphatase pathways, and higher-order effects on posttranslational modification of myocardial proteins.

Analysis of ARHGAP4 Expression With Colorectal Cancer Clinical Characteristics and Prognosis.

Background: This study aims to analyze the correlation between ARHGAP4 in the expression and clinical characteristics of colorectal cancer (CRC), and the influence of ARHGAP4 expression on the prognosis of CRC, and to evaluate whether ARHGAP4 is a potential prognostic oncotarget for CRC. Methods: ARHGAP4 was identified using the Gene Expression Omnibus database through weighted gene coexpression network analysis. Using the Gene Expression Profiling Interactive Analysis to perform and analyze the expression and prognosis of ARHGAP4 in CRC. The expression of AGRGAP4 and immune cells was analyzed by the Tumor IMmune Estimation Resource online database. Finally, immunohistochemistry was used to analyze the expression difference and prognosis of ARHGAP4 in CRC and adjacent normal tissues, as well as the relationship between AGRGAP4 expression and clinical features of CRC. Results: We identified ARHGAP4 that is related to the recurrence of CRC from GSE97781 data. ARHGAP4 has not been reported in CRC. The high expression of ARHGAP4 in select colon adenocarcinoma indicates a poor prognosis by database analysis. In our clinical data results, ARHGAP4 is highly expressed in CRC and lowly expressed in normal tissues adjacent to cancer. Compared with the low-expression group, the high-expression group has a significantly poorer prognosis. In colon cancer, the B-cell, macrophage, neutrophil, and dendritic-cell levels are downregulated after ARHGAP4 gene knockout; the levels of CD8+ and CD4+ T cells, neutrophils, and dendritic cells are upregulated after the amplification of the ARHGAP4 gene. In addition, ARHGAP4 expression is related to N,M staging and clinical staging. Conclusion: ARHGAP4 is highly expressed in CRC, and the high expression of ARHGAP4 has a poor prognosis. The expression of ARHGAP4 in CRC is related to the immune cells such as B cells, CD8+ and CD4+ T cells, macrophages, neutrophils, and dendritic cells. ARHGAP4 is correlated with N,M staging and clinical staging in CRC. ARHGAP4 may be a potential biomarker for the prognosis of CRC.

[Bacterial Community Structure and Antibiotic Resistance Gene Changes in IFAS+Magnetic Coagulation Process Wastewater Treatment Plant in Cold Regions].

The main objective of this study was to explore the changes in bacterial communities and antibiotic resistance genes (ARGs) in an integrated fixed-film activated sludge (IFAS)+magnetic coagulation process wastewater treatment plant (WWTP) in Xinjiang. The bacterial communities and ARGs in the influent, suspended activated sludge, attached biofilm, and effluent were studied using 16S rRNA gene sequencing and metagenomic sequencing. The results showed that the average relative abundances of Chloroflexi and Nitrospirae in activated sludge were 3.50% and 0.03%, respectively, and their relative abundances in biofilm reached 10.02% and 2.12%, respectively. The average removal rates of NH4+-N and TN increased from 91.89% and 66.76% to 97.71% and 91.90% after the reformation of this wastewater treatment plant, respectively, indicating that IFAS enhanced the biological nitrogen removal capacity of wastewater treatment plants in cold regions. The average relative abundances of Ferruginibacter and Rhodoferax related to iron redox in the biological treatment section were 5.24% and 3.72%, respectively, and the relative abundance of Rhodoferax in effluent reached 9.48%, indicating that the magnetic powder had an impact on the bacterial community. The IFAS wastewater treatment plant had an obvious removal effect on ARGs, and the relative abundance of ARGs decreased from 191.08×10-3‰ in the influent to 32.58×10-3‰ in the effluent. The relative abundance of ARGs in activated sludge was 63.25×10-3‰-72.38×10-3‰, which was significantly higher than 41.31×10-3‰ in biofilm. However, the relative abundances of dominant subtypes of ARGs such as sul2, floR, and rpoB2 in biofilm were 5.77×10-3‰, 2.52×10-3‰, and 2.03×10-3‰, respectively, which were higher than the 3.15×10-3‰-3.57×10-3‰, 1.73×10-3‰-2.24×10-3‰, and 1.28×10-3‰-1.76×10-3‰ in activated sludge. The network analysis indicated that Caldilineaceae_norank and Trichococcus were respectively positively correlated with sul2 and floR. These results can provide theoretical reference for the optimal operation and ARGs control of WWTPs in cold regions.

Spinocerebellar ataxia type 6 knockin mice develop a progressive neuronal dysfunction with age-dependent accumulation of mutant CaV2.1 channels.

Spinocerebellar ataxia type 6 (SCA6) is a neurodegenerative disorder caused by CAG repeat expansions within the voltage-gated calcium (Ca(V)) 2.1 channel gene. It remains controversial whether the mutation exerts neurotoxicity by changing the function of Ca(V)2.1 channel or through a gain-of-function mechanism associated with accumulation of the expanded polyglutamine protein. We generated three strains of knockin (KI) mice carrying normal, expanded, or hyperexpanded CAG repeat tracts in the Cacna1a locus. The mice expressing hyperexpanded polyglutamine (Sca6(84Q)) developed progressive motor impairment and aggregation of mutant Ca(V)2.1 channels. Electrophysiological analysis of cerebellar Purkinje cells revealed similar Ca(2+) channel current density among the three KI models. Neither voltage sensitivity of activation nor inactivation was altered in the Sca6(84Q) neurons, suggesting that expanded CAG repeat per se does not affect the intrinsic electrophysiological properties of the channels. The pathogenesis of SCA6 is apparently linked to an age-dependent process accompanied by accumulation of mutant Ca(V)2.1 channels.

Androgen down-regulated and region-specific expression of germ cell nuclear factor in mouse epididymis.

Germ cell nuclear factor (GCNF), a nuclear orphan receptor, involved in spermatogenesis, neurogenesis, differentiation, and embryo development, was highly expressed with two transcripts (7.4 and 2.3 kb) in mouse testis and with only one transcript (7.4 kb) slightly expressed in brain, liver, and kidney. The 2.3-kb transcript was restricted to round spermatids at stages VII and VIII of the spermatogenic cycle. The present report demonstrated its expression in epididymis as well, but at a very low level. Northern blot analysis showed two transcripts: a common 7.4-kb transcript and a unique 3.1-kb transcript. The expression levels of both GCNF transcripts in epididymis were down-regulated by androgen, as observed in castrated animals and aged mice. Polyclonal antisera against GCNF protein were raised. Western blot analysis showed the presence of only one band in total protein extracts from either mouse testis or epididymis. It indicated that the two mRNAs (7.4 and 3.1 kb) encode for the same protein as in testis. Fluorescent immunohistochemical staining and in situ hybridization showed that its expression was in the principal cell abundant in the corpus region. It implies that some androgen-regulated gene expressions located at the corpus principal cells might be controlled by GCNF.

Spatial and temporal expression of germ cell nuclear factor in murine epididymis.

AIM: To investigate the spatial and temporal expression of germ cell nuclear factor (GCNF) in mouse and rat epididymis during postnatal period. METHODS: The epididymal sections from different postnatal days were stained for GCNF by the indirect immunofluorescence technique and digital photographs were taken by a Carl Zeiss confocal microscope. RESULTS: GCNF was first detected on day 12 in mouse epididymis and day 14 in rat epididymis. The highest expression of GCNF was observed on day 35 in both mouse and rat epididymis. In adults, GCNF exhibited a region-specific expression pattern, i.e., it was expressed predominantly in the initial segment, caput and proximal corpus of rat epididymis and was abundant in the proximal corpus of mouse epididymis. GCNF could be found in the nuclei of the principal, apical, narrow, clear and halo cells. CONCLUSION: GCNF may play an important role in epididymal differentiation and development and in sperm maturation.

Phosphoinositol lipids bind to phosphatidylinositol 3 (PI3)-kinase enhancer GTPase and mediate its stimulatory effect on PI3-kinase and Akt signalings.

Phosphatidylinositol 3 (PI3)-kinase enhancer (PIKE) is a nuclear GTPase that enhances PI3-kinase activity in a GTP-dependent manner. Both PIKE-L and -A isoforms contain GTPase, pleckstrin homology (PH), ADP ribosylation factor-GTPase-activating protein, and two ankyrin repeats domains, and C-terminal ADP ribosylation factor-GTPase-activating protein activates its internal GTPase activity. However, whether PH domain modulates the intramolecular action and subsequently influences its downstream signalings remains elusive. Here we show that PH domain from PIKE-L robustly binds PI(3,4,5)P(3) and exclusively resides in the nucleus. By contrast, the mutant (K679,687N), unable to bind phosphoinositol lipids, translocates to the cytoplasm. This mutation substantially compromises the stimulatory effects on PI3-kinase by PIKE-L. Surprisingly, PH domain from PIKE-A distributes in the cytoplasm. Similar mutation in PH domain of PIKE-A abolishes its binding to PI(3,4,5)P(3) and significantly decreases its activation of Akt. Moreover, amplified PIKE-A from human cancers contains mutations and highly stimulates Akt kinase activity, correlating with its GTPase activity. Thus, phosphatidylinositols regulate PIKE GTPase activity, mediating its downstream PI3-kinase/Akt signaling through a feedback mechanism by binding to its PH domain.

Akt phosphorylates acinus and inhibits its proteolytic cleavage, preventing chromatin condensation.

Akt promotes cell survival by phosphorylating and inhibiting components of the intrinsic cell death machinery. Akt translocates into the nucleus upon exposure of cells to survival factors, but little is known about its functions in the nucleus. Here, we show that acinus, a nuclear factor required for apoptotic chromatin condensation, is a direct target of Akt. We demonstrate that Akt phosphorylation of acinus on serine 422 and 573 results in its resistance to caspase cleavage in the nucleus and the inhibition of acinus-dependent chromatin condensation. Abolishing acinus phosphorylation by Akt through mutagenesis accelerates its proteolytic degradation and chromatin condensation. Acinus S422, 573D, a mutant mimicking phosphorylation, resists against apoptotic cleavage and prevents chromatin condensation. Knocking down of acinus substantially decreases chromatin condensation, and depletion of Akt provokes the apoptotic cleavage of acinus. Thus, Akt inhibits chromatin condensation during apoptosis by phosphorylating acinus in the nucleus, revealing a specific mechanism by which nuclear Akt promotes cell survival.

PIKE-A is amplified in human cancers and prevents apoptosis by up-regulating Akt.

PIKE-A (PIKE-activating Akt), an isoform of PIKE GTPase that enhances phosphatidylinositol 3-kinase (PI3-kinase) activity, specifically binds to active Akt but not PI3-kinase. PIKE-A stimulates Akt activity in a GTP-dependent manner and promotes invasiveness of cancer cell lines. Here, we show that PIKE-A is amplified in a variety of human cancers and that amplified PIKE-A directly stimulates Akt and inhibits apoptosis compared to cells with normal PIKE-A copy number. Overexpression of PIKE-A wild-type but not dominant-negative mutant stimulates Akt activity and prevents apoptosis. Moreover, knockdown of PIKE-A diminishes Akt activity and increases apoptosis. Our findings suggest that PIKE-A amplification contributes to cancer cell survival and progression by inhibiting apoptosis through up-regulating Akt.