Evolutionary transfer of ORF-containing group I introns between different subcellular compartments (chloroplast and mitochondrion)

We describe here a case of homologous introns containing homologous open reading frames (ORFs) that are inserted at the same site in the large subunit (LSU) rRNA gene of different organelles in distantly related organisms. We show that the chloroplast LSU rRNA gene of the green alga Chlamydomonas pallidostigmatica contains a group I intron (CpLSU.2) encoding a site-specific endonuclease (I-CpaI). This intron is inserted at the identical site (corresponding to position 1931-1932 of the Escherichia coli 23S rRNA sequence) as a group I intron (AcLSU.m1) in the mitochondrial LSU rRNA gene of the amoeboid protozoon Acanthamoeba castellanii. The CpLSU.2 intron displays a remarkable degree of nucleotide similarity in both primary sequence and secondary structure to the AcLSU.m1 intron; moreover, the Acanthamoeba intron contains an ORF in the same location within its secondary structure as the CpLSU.2 ORF and shares with it a strikingly high level of amino acid similarity (65%; 42% identity). A comprehensive survey of intron distribution at site 1931 of the chloroplast LSU rRNA gene reveals a rather restricted occurrence within the polyphyletic genus Chlamydomonas, with no evidence of this intron among a number of non- Chlamydomonad green algae surveyed, nor in land plants. A parallel survey of homologues of a previously described and similar intron/ORF pair (C. reinhardtii chloroplast CrLSU/A. castellanii mitochondrial AcLSU.m3) also shows a restricted occurrence of this intron (site 2593) among chloroplasts, although the intron distribution is somewhat broader than that observed at site 1931, with site-2593 introns appearing in several green algal branches outside of the Chlamydomonas lineage. The available data, while not definitive, are most consistent with a relatively recent horizontal transfer of both site-1931 and site- 2593 introns (and their contained ORFs) between the chloroplast of a Chlamydomonas-type organism and the mitochondrion of an Acanthamoeba- like organism, probably in the direction chloroplast to mitochondrion. The data also suggest that both introns could have been acquired in a single event.      

A Biochemical Study of Spore Germination in the Blue-green Alga Anabaena doliolum

The spores of Anabaena doliolum formed in light (light spores)and after transfer to darkness (dark spores) are biochemicallydifferent in that the light spores contain chlorophyll a andphycocyanin, while dark spores seem to lack them. The apparentbiosyntheses accompanying dark-spore germination seem to proceedin the following order: RNA, chlorophyll a, phycocyanin andDNA. Results of chloramphenicol treatment indicate that proteinsynthesis precedes RNA synthesis. The biosynthetic events followingRNA synthesis show a requirement for light.     

The Adult G?ttingen Minipig as a Model for Chronic Heart Failure After Myocardial Infarction: Focus on Cardiovascular Imaging and Regenerative Therapies

Porcine models have become increasingly popular in cardiovascular research. The standard farm pig rapidly increases in body weight and size, potentially confounding serial measurements of cardiac function and morphology. We developed an adult porcine model that does not show physiologic increases in heart mass during the study period and is suitable for long-term study. We compared adult minipigs with the commonly used adolescent Yorkshire swine. Myocardial infarction was induced in adult Göttingen minipigs and adolescent Yorkshire swine by occlusion of the left anterior descending coronary artery followed by reperfusion. At 8 wk after infarction, the left ventricular ejection fraction was 34.1 ± 2.3% in minipigs and 30.7 ± 2.0% in Yorkshire swine. The left ventricular end-diastolic mass in Yorkshire pigs assessed by magnetic resonance imaging increased 17 ± 5 g, from 42.6 ± 4.3 g at week 1 after infarction to 52.8 ± 6.6 g at week 8, whereas it remained unchanged in minipigs. Cardiac anatomy and physiology in adult minipigs were evaluated invasively by angiography and noninvasively by Multidetector Computed Tomography and by Magnetic Resonance Imaging at 1.5 T and 3 T prior to myocardial infarction and during folow-up. This porcine heart failure model is reproducible, mimics the pathophysiology in patients who have experienced myocardial infarction, and is suitable for imaging studies. New heart failure therapies and devices can be tested preclinically in this adult animal model of chronic heart failure.Abbreviations: CEMRA, contrast-enhanced magnetic resonance angiography; CI, confidence interval; ECG, electrocardiogram; LAD, left anterior descending artery; LV, left ventricle; LVEF, left ventricular ejection fraction; MDCT, multidetector computed tomography; MI, myocardial infarction; MRI, magnetic resonance imagingIn the United States alone, 7.1 million people are survivors of myocardial infarction (MI) and 4.9 million people live with congestive heart failure.⁴ New medical therapies, surgical procedures and devices for heart failure all rely heavily on preclinical testing in animal models. Porcine models of MI are used because of the similarities between porcine and human hearts.^29,38 However, the commonly employed farm pigs are utilized at a young age, grow rapidly and continue to gain in mass during use, thereby complicating long-term follow-up. The utilization of farm pigs at a young age, while their hearts are still growing does not accurately reflect the remodeling that occurs in adult patients after MI and can limit accurate assessment of chronic remodeling processes. This inaccuracy can confound evaluation of devices and pharmacologic therapies.Noninvasive imaging techniques for determining anatomic and functional manifestations of congestive heart failure are accurate and reliable, and are used as surrogate markers of outcome and safety in phase I/II trials.^15,34 Cardiovascular imaging improves evaluation of the effects of new therapies and devices during preclinical assessment. Animal models of congestive heart failure should allow noninvasive imaging during a long-term follow-up period.The Göttingen minipig was developed in the early 1960s at the Institute of Animal Breeding and Genetics (University of Göttingen, Germany) to reduce space requirements and housing costs for preclinical porcine studies.⁹ They were created by crossbreeding the Minnesota minipig with Vietnamese potbelly and German Landrace pigs.¹⁹ Göttingen minipigs are white miniature pigs with good fertility and stable genetics.Göttingen minipigs have a characteristic growth curve that avoids the dramatic increase in weight in adulthood seen in farm pigs.^25,26 A newborn Göttingen minipig has a body mass of 350 to 450 g. Boars become sexually mature at 3 to 4 mo of age, weighing 6 to 8 kg, whereas sows become sexually mature at 4 to 5 mo and 7 to 9 kg. The gestational period is 112 to 114 d, and the average litter size is 5 to 6 animals. Closure of the growth plates is complete at 18 to 22 mo and 30 to 35 kg. Göttingen minipigs have a mature body weight of 35 to 45 kg,¹⁰ and they achieve 40% of the maximal body weight at approximately 10 mo (310 d) with a body weight of 21 kg. In comparison intensively fed farm pigs reach 88 kg at the same time point, with a mature weight of 220 kg, and restrictively fed farm pigs, like Yorkshire swine, typically weigh about 64 kg at 10 mo of age and 160 kg at maturity.²⁶ Characteristics of Yorkshire swine are reported in the literature.¹¹Adult Göttingen minipigs are large enough to allow testing of human equipment and devices. Until now cardiovascular parameters have only been reported in juvenile Göttingen minipigs.^9,13 Here, we demonstrate the unique value of Göttingen minipigs as a novel adult porcine heart failure model for cardiac research in the fields of regenerative medicine, electrophysiology, and noninvasive imaging.     

Chemical biology: Paper alert

A selection of interesting papers that were published in the two months before our press date in major journals most likely to report significant results in chemical biology.     

A critical review on brain and heart axis response in COVID-19 patients: Molecular mechanisms,mediators, biomarkers,and therapeutics

Since the outbreak of highly virulent coronaviruses, significant interest was assessed to the brain and heart axis (BHA) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-affected patients. The majority of clinical reports accounted for unusual symptoms associated with SARS-CoV-2 infections which are of the neurological type, such as headache, nausea, dysgeusia, anosmia, and cerebral infarction. The SARS-CoV-2 enters the cells through the angiotensin-converting enzyme (ACE-2) receptor. Patients with prior cardiovascular disease (CVD) have a higher risk of COVID-19 infection and it has related to various cardiovascular (CV) complications. Infected patients with pre-existing CVDs are also particularly exposed to critical health outcomes. Overall, COVID-19 affected patients admitted to intensive care units (ICU) and exposed to stressful environmental constraints, featured with a cluster of neurological and CV complications. In this review, we summarized the main contributions in the literature on how SARS-CoV-2 could interfere with the BHA and its role in affecting multiorgan disorders. Specifically, the central nervous system involvement, mainly in relation to CV alterations in COVID-19-affected patients, is considered. This review also emphasizes the biomarkers and therapy options for COVID-19 patients presenting with CV problems.