Lifeboat Foundation

Cytokine mediated sustained inflammation increases the risk to develop different complex chronic inflammatory diseases, such as inflammatory bowel disease (IBD). Recent studies highlighted the involvement of inflammation associated gene variants in m6A methylation. Moreover, long noncoding RNAs (lncRNAs) participate in the pathogenesis of inflammatory disorders and their function can be influenced by differential methylation. Here we describe the functional implication of LOC339803 lncRNA in the development of IBD. We found that allele-specific m6A methylation affects YTHDC1 mediated protein binding affinity. LOC339803-YTHDC1 interaction dictates chromatin localization of LOC339803 ultimately inducing IL1B and contributing to the development of intestinal inflammation. Our findings were confirmed using human intestinal biopsy samples from IBD and controls. Overall, our results support LOC339803 lncRNA as an important mediator of intestinal inflammation, presenting this lncRNA as a potential novel therapeutic target for the treatment of IBD.

The authors have declared no competing interest.

CRISPR/Cas9 technology-mediated genome editing has significantly improved the targeted inactivation of genes in vitro and in vivo in many organisms. In this study, we have reported a novel CRISPR-based vector system for conditional tissue-specific gene ablation in zebrafish. Specifically, the cardiac-specific cardiac myosins light chain 2 (cmlc2) promoter drives Cas9 expression to silence the neuropilin-1(nrp1) gene in cardiomyocytes in a heat-shock inducible manner. This vector system establishes a unique tool to regulate the gene knockout in both the developmental and adult stages and hence, widens the possibility of loss-of-function studies in zebrafish at different stages of development and adulthood. Using this approach, we investigated the role of neuropilin isoforms nrp1a and nrp1b in response to cardiac injury and regeneration in adult zebrafish hearts. We observed that both the isoforms (nrp1a and nrp1b) are upregulated after the cryoinjury. Interestingly, the nrp1b-knockout significantly altered heart regeneration and impaired cardiac function in the adult zebrafish, demonstrated by reduced heart rate (ECG), ejection fractions, and fractional shortening. In addition, we show that the knockdown of nrp1b but not nrp1a induces activation of the cardiac remodeling genes in response to cryoinjury. To our knowledge, this is the first study where we have reported a heat shock-mediated conditional knockdown of nrp1a and nrp1b isoforms using CRISPR/Cas9 technology in the cardiomyocyte in zebrafish, and furthermore have identified a crucial role for nrp1b isoform in zebrafish cardiac remodeling and eventually heart function in response to injury.

The authors have declared no competing interest.

At team of researchers at Stanford University reports evidence that people who engage in cyclic sighing breathing exercises see a greater reduction in stress than those engaging in mindfulness meditation. In their paper published in the journal Cell Reports Medicine, the researchers describe their study of several different types of stress reduction techniques.

Prior research has shown that while stress can be a positive influence at times, such as when it prompts people to do things they know they need to do, more often, it is considered adverse because it can lead to health problems such as hypertension. Thus, stress techniques have been developed to help people reduce stress without resorting to drugs. One such technique is mindfulness meditation, during which a person attempts to relax by putting themselves in the moment in a nonjudgmental way for a period of time. Other techniques involve engaging in breathing exercises. In this new effort, the researchers compared three types of breathing exercises and mindfulness meditation to assess their effectiveness.

The three types of breathing exercises tested included cyclic sighing, in which more time and thought is spent on exhaling than on inhaling or holding the breath; box breathing, in which breathing and holding are done for the same amount of time; and cyclic hyperventilation, in which inhalations last longer than exhalations.

Analyzing a person’s gene expression requires mapping their RNA landscape to a standard reference to gain insight into the degree to which genes are “turned on” and perform functions in the body. But researchers can run into issues when the reference does not provide enough information to allow for accurate mapping, an issue known as reference bias.

In a new paper published in the journal Nature Methods, researchers at UC Santa Cruz introduce the first-ever method for analyzing RNA sequencing data genome-wide using a “pantranscriptome,” which combines a transcriptome and a pangenome—a reference that contains genetic material from a cohort of diverse individuals, rather than just a single linear strand.

A group of scientists led by UCSC Associate Professor of Biomolecular Engineering Benedict Paten have released a toolkit that allows researchers to map an individual’s RNA data to a much richer reference, addressing reference bias and leading to much more accurate mapping.

Scientists at University of Galway delved into the issue of antimicrobial resistance—one of the greatest threats to human health—discovering the potential to improve treatment options for superbug MRSA infections using penicillin-type antibiotics that have become ineffective on their own.

The research has been published in the journal mBio.

Professor James P O’Gara and Dr. Merve S Zeden in the School of Biological and Chemical Sciences, University of Galway, led the study.

Many genetic diseases are caused by diverse mutations spread across an entire gene, and designing genome editing approaches for each patient’s mutation would be impractical and costly.

Investigators at Massachusetts General Hospital (MGH) have recently developed an optimized method that improves the accuracy of inserting large DNA segments into a genome.

This approach could be used to insert a whole normal or “wild-type” replacement gene, which could act as a blanket therapy for a disease irrespective of a patient’s particular mutation.

Scientists continue to expand the technological frontiers of CRISPR, along with its enormous potential, in areas ranging from human health to global food supplies. Such is the case with CRISPR-based gene drives, a genetic editing tool designed to influence how genetic elements are passed from one generation to the next.

Gene drives designed for mosquitoes have the potential to curb the spread of malarial infections that cause hundreds of thousands of deaths each year, yet safety issues have been raised because such drives can spread quickly and dominate entire populations. Scientists have explored the principles governing the spread of gene-drive elements in targeted populations such as mosquitoes by testing many different combinations of components that constitute the drive apparatus. They have found, however, that there’s still more to explore and that key questions remain.

In the journal Nature Communications, University of California San Diego researchers led by former Postdoctoral Scholar Gerard Terradas, together with Postdoctoral Scholar Zhiqian Li and Professor Ethan Bier, in close collaboration with UC Berkeley graduate student Jared Bennett and Associate Professor John Marshall, describe the development of a new system for testing and developing gene drives in the laboratory and safely converting them into tools for potential real-world applications.

Scientists have developed a wireless, battery-free implant capable of monitoring dopamine signals in the brain in real-time in small animal models, an advance that could aid in understanding the role neurochemicals play in neurological disorders.

The device, detailed in a study published in ACS Nano, activates or inhibits specific neurons in the brain using light, a technique known as optogenetic stimulation. It also records dopamine activity in freely behaving subjects without the need for bulky or prohibitive sensing equipment, said John Rogers, Ph.D., the Louis Simpson and Kimberly Querrey Professor of Materials Science and Engineering, Biomedical Engineering and Neurological Surgery, and a co-author of the study.

“This device allows neuroscientists to monitor and modulate brain activity in real-time and in a programmable fashion, in mice—a very important class of animal model for neuroscience studies,” Rogers said.

New tools and methods have been described by WEHI researchers to study an unusual protein modification and gain fresh insights into its roles in human health and disease.

The study—about how certain sugars modify proteins—was published today in Nature Chemical Biology. Led by WEHI researcher Associate Professor Ethan Goddard-Borger, this work lays a foundation for better understanding diseases like muscular dystrophy and cancer.