YTHDF2 governs muscle size through a targeted modulation of proteostasis.

The regulation of proteostasis is fundamental for maintenance of muscle mass and function. Activation of the TGF-ß pathway drives wasting and premature aging by favoring the proteasomal degradation of structural muscle proteins. Yet, how this critical post-translational mechanism is kept in check to preserve muscle health remains unclear. Here, we reveal the molecular link between the post-transcriptional regulation of m6A-modified mRNA and the modulation of SMAD-dependent TGF-ß signaling. We show that the m6A-binding protein YTHDF2 is essential to determining postnatal muscle size. Indeed, muscle-specific genetic deletion of YTHDF2 impairs skeletal muscle growth and abrogates the response to hypertrophic stimuli. We report that YTHDF2 controls the mRNA stability of the ubiquitin ligase ASB2 with consequences on anti-growth gene program activation through SMAD3. Our study identifies a post-transcriptional to post-translational mechanism for the coordination of gene expression in muscle.

Loss of YTHDF2 Alters the Expression of m6A-Modified Myzap and Causes Adverse Cardiac Remodeling.

How post-transcriptional regulation of gene expression, such as through N6-methyladenosine (m6A) messenger RNA methylation, impacts heart function is not well understood. We found that loss of the m6A binding protein YTHDF2 in cardiomyocytes of adult mice drove cardiac dysfunction. By proteomics, we found myocardial zonula adherens protein (MYZAP) within the top up-regulated proteins in knockout cardiomyocytes. We further demonstrated that YTHDF2 binds m6A-modified Myzap messenger RNA and controls its stability. Cardiac overexpression of MYZAP has been associated with cardiomyopathy. Thus, our findings provide an important new mechanism for the YTHDF2-dependent regulation of this target and therein its novel role in the maintenance of cardiac homeostasis.

Clarification of acid site location in MSE-type zeolites by spectroscopic approaches combined with catalytic activity: comparison between UZM-35 and MCM-68.

MSE-type zeolites synthesized by different organic structure-directing agents (OSDAs), UZM-35 and MCM-68, were prepared. The location of Brønsted acid sites derived from the framework Al atoms and acidic properties were investigated based on 27Al MQMAS NMR and in situ IR techniques combined with the evaluation of the catalytic activity. We have successfully found a significant difference in the location of Brønsted acid sites in the MSE-type framework; 61 and 33% of acid sites were located at the 12-ring channel for MCM-68 and UZM-35, respectively. The differences in the location of the acid sites yielded their unique catalytic activities for the hydrocarbon cracking reactions, indicating that a well-chosen type of OSDAs for the synthesis is one of the possibilities for controlling the distribution of the framework Al atoms in the MSE-type framework.

ERK1/2: An Integrator of Signals That Alters Cardiac Homeostasis and Growth.

Integration of cellular responses to extracellular cues is essential for cell survival and adaptation to stress. Extracellular signal-regulated kinase (ERK) 1 and 2 serve an evolutionarily conserved role for intracellular signal transduction that proved critical for cardiomyocyte homeostasis and cardiac stress responses. Considering the importance of ERK1/2 in the heart, understanding how these kinases operate in both normal and disease states is critical. Here, we review the complexity of upstream and downstream signals that govern ERK1/2-dependent regulation of cardiac structure and function. Particular emphasis is given to cardiomyocyte hypertrophy as an outcome of ERK1/2 activation regulation in the heart.

Epitranscriptomics in the Heart: a Focus on m6A.

PURPOSE OF REVIEW: Post-transcriptional modifications are key regulators of gene expression that allow the cell to respond to environmental stimuli. The most abundant internal mRNA modification is N6-methyladenosine (m6A), which has been shown to be involved in the regulation of RNA splicing, localization, translation, and decay. It has also been implicated in a wide range of diseases, and here, we review recent evidence of m6A's involvement in cardiac pathologies and processes. RECENT FINDINGS: Studies have primarily relied on gain and loss of function models for the enzymes responsible for adding and removing the m6A modification. Results have revealed a multifaceted role for m6A in the heart's response to myocardial infarction, pressure overload, and ischemia/reperfusion injuries. Genome-wide analyses of mRNAs that are differentially methylated during cardiac stress have highlighted the importance of m6A in regulating the translation of specific categories of transcripts implicated in pathways such as calcium handling, cell growth, autophagy, and adrenergic signaling in cardiomyocytes. Regulation of gene expression by m6A is critical for cardiomyocyte homeostasis and stress responses, suggesting a key role for this modification in cardiac pathophysiology.

Quantification of the Mean and Distribution of Hemoglobin Content in Normal Human Blood Using Cell Tracking Velocimetry.

The current clinical method for detecting anemia focuses on measuring the concentration of hemoglobin (Hb) in blood. However, recent developments in particle tracking algorithms and the understanding of the relationship between Hb and magnetism has enabled the quantitative measurement of the Hb content in a single red blood cell, RBC, based on magnetophoretic mobility. To further explore this relationship, 22 human blood samples obtained from 17 healthy volunteers were analyzed by the cell tracking velocimetry system, and the calculated Hb concentration from these measurements was compared to the values measured by UV-visible spectrophotometry, the standard method for measuring Hb in clinical laboratories. The results show close correlations between the mean of the spectrophotometric and magnetophoretic methods; however, single cell analysis with the magnetophoretic mobility method allows further elucidation of the distribution of Hb concentration within RBCs from a donor sample to be determined. Histograms of these magnetophoretic mobility distributions indicate that the fraction of RBCs that are below the bulk Hb concentration that defines anemia varies not only from donor to donor but also in the same donor over time. Consistent with a variable fraction below the anemic Hb concentration, the distribution around the mean has a large range. Previous studies have indicated that RBCs lose Hb during ex vivo storage; however, it is not known if this variability in the distribution of Hb content is a function of the age of the RBCs in a donor, suggesting a variable rate in RBC production between donors, or variability in available iron at the time of RBC formation. We suggest our cell tracking velocimetry system can reveal more information regarding this matter.

Production of p-xylene from biomass by catalytic fast pyrolysis using ZSM-5 catalysts with reduced pore openings.

Pores for thought: Chemical liquid deposition of silica onto ZSM-5 catalysts led to smaller pore openings that resulted in >90% selectivity for p-xylene over the other xylenes in the catalytic fast pyrolysis of furan and 2-methylfuran (see scheme). The p-xylene selectivity increased from 51% with gallium spray-dried ZSM-5 to 72% with a pore-mouth-modified catalyst in the pyrolysis of pine wood.

The sweat test: effect of elution time on chloride and sodium concentrations.

BACKGROUND: The National Committee for Clinical Laboratory Standards guidelines and Guidelines for the Performance of the Sweat Test for the Diagnosis of Cystic Fibrosis in the United Kingdom recommend that sweat be eluted from filter paper for a minimum of 40 min. In the absence of published data, this recommendation is based on expert opinion. We therefore investigated the effect of elution time on chloride and sodium concentrations. METHODS: The effect of elution time (up to three hours) on chloride and sodium concentrations was studied as recommended for measurement of quality control samples using external quality assessment solutions. RESULTS: There were no significant differences in eluted chloride and sodium concentrations with time of elution up to 3 h. CONCLUSION: Elution time within 3 h had no effect on chloride and sodium concentrations when eluted from filter paper.