Left bundle branch block cardiomyopathy (LBBB-CMP): from the not-so-benign finding of idiopathic LBBB to LBBB-CMP diagnosis and treatment.

Unlabelled: Introduction Idiopathic left bundle branch block (iLBBB) is an uncommon finding. Its benignity has been increasingly questioned, though its natural history remains poorly clarified. Similarly, LBBB-cardiomyopathy (LBBB-CM) has been also increasingly recognized as a distinct entity, where electromechanical dyssynchrony seems to play a central role in left ventricular dysfunction (LVD) development.

Ancestral aneuploidy and stable chromosomal duplication resulting in differential genome structure and gene expression control in trypanosomatid parasites.

Aneuploidy is widely observed in both unicellular and multicellular eukaryotes, usually associated with adaptation to stress conditions. Chromosomal duplication stability is a tradeoff between the fitness cost of having unbalanced gene copies and the potential fitness gained from increased dosage of specific advantageous genes. Trypanosomatids, a family of protozoans that include species that cause neglected tropical diseases, are a relevant group to study aneuploidies.

Acute myocardial infarction during late COVID-19 era: patient characteristics, presentation and outcomes.

COVID-19 pandemic has unquestionably influenced care of acute myocardial infarction (AMI). Still, its impact on patients (pts) characteristics, presentation, treatment, and outcomes remains not well established in late pandemic times. To address this issue, we performed a prospective study of type-1 AMI patients admitted in a tertiary care hospital.

Genome duplication in relies on persistent subtelomeric DNA replication.

DNA replication is needed to duplicate a cell's genome in S phase and segregate it during cell division. Previous work in detected DNA replication initiation at just a single region in each chromosome, an organisation predicted to be insufficient for complete genome duplication within S phase. Here, we show that acetylated histone H3 (AcH3), base J and a kinetochore factor co-localise in each chromosome at only a single locus, which corresponds with previously mapped DNA replication initiation regions and is demarcated by localised G/T skew and G4 patterns.

Persistent DNA Damage Foci and DNA Replication with a Broken Chromosome in the African Trypanosome.

Damaged DNA typically imposes stringent controls on eukaryotic cell cycle progression, ensuring faithful transmission of genetic material. Some DNA breaks, and the resulting rearrangements, are advantageous, however. For example, antigenic variation in the parasitic African trypanosome, , relies upon homologous recombination-based rearrangements of telomeric variant surface glycoprotein () genes, triggered by breaks.

Conservation and Variation in Strategies for DNA Replication of Kinetoplastid Nuclear Genomes.

Introduction: Understanding how the nuclear genome of kinetoplastid parasites is replicated received experimental stimulus from sequencing of the Leishmania major, Trypanosoma brucei and Trypanosoma cruzi genomes around 10 years ago. Gene annotations suggested key players in DNA replication initiation could not be found in these organisms, despite considerable conservation amongst characterised eukaryotes. Initial studies that indicated trypanosomatids might possess an archaeal-like Origin Recognition Complex (ORC), composed of only a single factor termed ORC1/CDC6, have been supplanted by the more recent identification of an ORC in T.

Nuclear DNA Replication in Trypanosomatids: There Are No Easy Methods for Solving Difficult Problems.

In trypanosomatids, etiological agents of devastating diseases, replication is robust and finely controlled to maintain genome stability and function in stressful environments. However, these parasites encode several replication protein components and complexes that show potentially variant composition compared with model eukaryotes. This review focuses on the advances made in recent years regarding the differences and peculiarities of the replication machinery in trypanosomatids, including how such divergence might affect DNA replication dynamics and the replication stress response.

Does DNA replication direct locus-specific recombination during host immune evasion by antigenic variation in the African trypanosome?

All pathogens must survive host immune attack and, amongst the survival strategies that have evolved, antigenic variation is a particularly widespread reaction to thwart adaptive immunity. Though the reactions that underlie antigenic variation are highly varied, recombination by gene conversion is a widespread approach to immune survival in bacterial and eukaryotic pathogens. In the African trypanosome, antigenic variation involves gene conversion-catalysed movement of a huge number of variant surface glycoprotein (VSG) genes into a few telomeric sites for VSG expression, amongst which only a single site is actively transcribed at one time.

Mapping replication dynamics in Trypanosoma brucei reveals a link with telomere transcription and antigenic variation.

Survival of Trypanosoma brucei depends upon switches in its protective Variant Surface Glycoprotein (VSG) coat by antigenic variation. VSG switching occurs by frequent homologous recombination, which is thought to require locus-specific initiation. Here, we show that a RecQ helicase, RECQ2, acts to repair DNA breaks, including in the telomeric site of VSG expression.

Diverged composition and regulation of the Trypanosoma brucei origin recognition complex that mediates DNA replication initiation.

Initiation of DNA replication depends upon recognition of genomic sites, termed origins, by AAA+ ATPases. In prokaryotes a single factor binds each origin, whereas in eukaryotes this role is played by a six-protein origin recognition complex (ORC). Why eukaryotes evolved a multisubunit initiator, and the roles of each component, remains unclear.

Genome-wide mapping reveals single-origin chromosome replication in Leishmania, a eukaryotic microbe.

Background: DNA replication initiates on defined genome sites, termed origins. Origin usage appears to follow common rules in the eukaryotic organisms examined to date: all chromosomes are replicated from multiple origins, which display variations in firing efficiency and are selected from a larger pool of potential origins. To ask if these features of DNA replication are true of all eukaryotes, we describe genome-wide origin mapping in the parasite Leishmania.

Single molecule analysis of Trypanosoma brucei DNA replication dynamics.

Eukaryotic genome duplication relies on origins of replication, distributed over multiple chromosomes, to initiate DNA replication. A recent genome-wide analysis of Trypanosoma brucei, the etiological agent of sleeping sickness, localized its replication origins to the boundaries of multigenic transcription units. To better understand genomic replication in this organism, we examined replication by single molecule analysis of replicated DNA.

Nuclear DNA replication initiation in kinetoplastid parasites: new insights into an ancient process.

Nuclear DNA replication is, arguably, the central cellular process in eukaryotes, because it drives propagation of life and intersects with many other genome reactions. Perhaps surprisingly, our understanding of nuclear DNA replication in kinetoplastids was limited until a clutch of studies emerged recently, revealing new insight into both the machinery and genome-wide coordination of the reaction. Here, we discuss how these studies suggest that the earliest acting components of the kinetoplastid nuclear DNA replication machinery - the factors that demarcate sites of the replication initiation, termed origins - are diverged from model eukaryotes.

Imidazoquines as antimalarial and antipneumocystis agents.

Peptidomimetic imidazolidin-4-one derivatives of primaquine (imidazoquines) recently displayed in vitro activity against blood schizonts of a chloroquine-resistant strain of Plasmodium falciparum. Preliminary studies with a subset of such imidazoquines showed them to both block transmission of P. berghei malaria from mouse to mosquito and be highly stable toward hydrolysis at physiological conditions.

Plasmodium berghei-infection induces volume-regulated anion channel-like activity in human hepatoma cells.

Parasite infection can lead to alterations in the permeability of host plasma membranes. Presented here is the first demonstration that this phenomenon occurs in Plasmodium-infected liver cells. Using the whole-cell patch-clamp technique, volume-regulated anion channel (VRAC) activity was characterized in Huh-7 cells (a human hepatoma cell line) before and after infection with Plasmodium berghei.