Scientific Highlights: by publication date

2. Journal of Experimental Medicine

CNIC scientists produce an atlas of genes mutated byan immune-system protein and linked to lymphoma

Researchers at the CNIC have identified the largest collection to date of genes mutated by AID, a key protein in the immune response. The study reveals a new link between themutagenic activity of AID and the generation of lymphomas. The information obtained, published in the Journal of Experimental Medicine, will increase understanding of the molecular mechanisms that control the activity of this enzyme and its possible contribution to the development of cancer. The research team led by Almudena Ramiro has compiled an atlas of the mutations that accumulate in the DNA of B lymphocytes during the immune response.

Álvarez-Prado ÁF, Pérez-Durán P, Pérez-García A, Benguria A, Torroja C, de Yébenes VG, Ramiro AR. A broad atlas of somatic hypermutation allows prediction of activation-induced deaminase targets. J Exp Med. 2018;215(3):761-71. doi: 10.1084/ jem.20171738

4. Nature Communications

CNIC scientists describe a mechanism of heart regeneration in the zebrafish

Some animals, including the zebrafish, have a high capacity to regenerate tissues, allowing them to recovery fully after cardiac injury. During this process, the heart muscle cells divide to replace the damaged tissue. However, there has been uncertainty about whether all cells contribute equally to the reconstruction of the heart wall. Now, a team of scientists led by Nadia Mercader at the CNIC and the University of Bern (Switzerland), working with collaborators at the University of Zurich (Switzerland), have discovered a high level of plasticity among the cells of the zebrafish heart muscle. The study is published in Nature Communications.

After a heart attack, the human heart loses millions of cardiomyocytes, the cells that form the muscle wall. In contrast, other animal species have a high regenerative capacity, enabling them to replace the injured myocardium with new cardiomyocytes. One such species is the zebrafish (Danio rerio). According to first author Héctor Sánchez-Iranzo, the zebrafish “is a widely used model system in cardiovascular research into the mechanisms controlling regeneration, and an inspiration for attempts to develop future regenerative therapies.”

Sánchez-Iranzo H, Galardi-Castilla M, Minguillón C, Sanz-Morejón A, González-Rosa JM, Felker A, Ernst A, Guzmán-Martínez G, Mosimann C, Mercader N. Tbx5a lineage tracing shows cardiomyocyte plasticity during zebrafish heart regeneration. Nat Commun. 2018;9(1):428. doi: 10.1038/s41467-017- 02650-6

6. Circulation

Scientists discover the cause of accelerated atherosclerosis and premature death in progeria

Scientists at the CNIC and the CIBER de Enfermedades Cardiovasculares (CIBERCV), led by Vicente Andrés, have generated the first genetically modified mice with accelerated atherosclerosis induced by the protein progerin, which causes the development of HGPS. The research team found that the main cause of accelerated atherosclerosis and premature death in these mice was alterations in the smooth muscle cells lining the blood vessels. The results of the study, published in Circulation, identify vascular smooth muscle cells as a possible therapeutic target for combatting the premature atherosclerosis in progeria. The study was conducted in collaboration with Carlos López-Otín of the University of Oviedo and Jacob Bentzon at the CNIC.

Hamczyk MR, Villa-Bellosta R, Gonzalo P, Andrés- Manzano MJ, Nogales P, Bentzon JF, López-Otín C, Andrés V. Vascular Smooth Muscle-Specific Progerin Expression Accelerates Atherosclerosis and Death in a Mouse Model of Hutchinson-Gilford Progeria Syndrome. Circulation. 2018;138(3):166-82. doi: 10.1161/CIRCULATIONAHA.117.030856

Communications, contribute to the understanding of the cellular processes initiated at early stages and explain how the distinct cell populations of the immune system communicate to mount an effective response against pathogens. The CNIC researchers have shown that mitochondrial DNA contained in nanovesicles triggers a state of alertness in recipient cells that activates an antiviral genetic program. These nanovesicles, known as exosomes, are produced by T lymphocytes and taken up by dendritic cells via intercellular contacts.

Torralba D, Baixauli F, Villarroya-Beltri C, Fernández- Delgado I, Latorre-Pellicer A, Acín-Pérez R, Martín- Cófreces NB, Jaso-Tamame ÁL, Iborra S, Jorge I, González-Aseguinolaza G, Garaude J, Vicente- Manzanares M, Enríquez JA, Mittelbrunn M, Sánchez-Madrid F. Priming of dendritic cells by DNA- containing extracellular vesicles from activated T cells through antigen-driven contacts. Nat Commun. 2018;9(1):2658. doi: 10.1038/s41467-018-05077-9

9. PLoS Biology

P38 alpha: the switch controlling obesity and diabetes

One of the research lines targeting the worldwide obesity epidemic is the manipulation of brown fat, a ‘good’ type of fat tissue that burns lipids to maintain an appropriate body temperature. Researchers at the CNIC have now uncovered the mechanism by which brown fat cells are activated to generate heat and eliminate excess fat. The results, published in PLoS Biology, have potential clinical implications for the treatment of obesity and related diseases like diabetes.

plays an important role in the day-to-day function of healthy organs. The research results show that the immune cells called neutrophils help to maintain the normal function of healthy tissues.

Casanova-Acebes M, Nicolás-Ávila JA, Li JL, García- Silva S, Balachander A, Rubio-Ponce A, Weiss LA, Adrover JM, Burrows K, A-González N, Ballesteros I, Devi S, Quintana JA, Crainiciuc G, Leiva M, Gunzer M, Weber C, Nagasawa T, Soehnlein O, Merad M, Mortha A, Ng LG, Peinado H, Hidalgo A.Neutrophils instruct homeostatic and pathological states in naive tissues. J Exp Med. 2018;215(11):2778-95. doi: 10.1084/jem.20181468 10.1084/jem.20171738

11. Science

A new mechanism in the control of inflammation

In response to infection or tissue injury, our bodies react by activating the inflammatory immune response, which attacks the infection and repairs the damaged tissue. However, excess inflammation can sometimes have the opposite effect, increasing injury in a process known as immunopathology. Now, researchers at the CNIC have discovered a new inflammation control mechanism that shows how the damage caused by the immune response can be controlled. The study is published in Science.

Del Fresno C, Saz-Leal P, Enamorado M, Wculek SK, Martínez-Cano S, Blanco-Menéndez N, Schulz O, Gallizioli M, Miró-Mur F, Cano E, Planas A, Sancho D. DNGR-1 in dendritic cells limits tissue damage by dampening neutrophil recruitment. Science. 2018;362(6412):351-6. doi: 10.1126/science. aan8423


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