Characterization of experimental cerebral malaria by volumetric MRI A comparative study across the sexes.

Cerebral malaria (CM), a potentially lethal neurological complication of the infection by Plasmodium falciparum, affects mostly the pediatric population under 5 years old in sub-Saharan Africa. This clinical syndrome is characterized on anatomical brain imaging by microhemorrhages, parenchymal lesions and brain edema. Epidemiological studies based on sex or gender are rare and do not allow to draw any conclusions on a possible sexual dimorphism in CM.

Resveratrol protection against cardiac remodeling and ischemia-reperfusion injury associated with hepatic lipid metabolism ameliorations and adipose tissue autotaxin pathway inhibition in a diet induced prediabetic female rat model.

Prediabetes is associated with an increased CV risk, especially for women. Recent evidence highlights the importance of liver and adipose tissue (AT) in its stratification. Current therapeutic strategies lack cardioprotective effects in this context.

Contribution of Magnetic Resonance Imaging Studies to the Understanding of Cerebral Malaria Pathogenesis.

Cerebral malaria (CM), the most lethal clinical syndrome of infection, mostly affects children under 5 in sub-Saharan Africa. CM is characterized by seizures and impaired consciousness that lead to death in 15-20% of cases if treated quickly, but it is completely fatal when untreated. Brain magnetic resonance imaging (MRI) is an invaluable source of information on the pathophysiology of brain damage, but, due to limited access to scanners in endemic regions, only until very recently have case reports of CM patients studied with advanced MRI methods been published.

Cyclosporine A Delays the Terminal Disease Stage in the Tfam KO Mitochondrial Myopathy Mouse Model Without Improving Mitochondrial Energy Production.

Introduction And Aims: Mitochondrial myopathies are rare genetic disorders for which no effective treatment exists. We previously showed that the pharmacological cyclophilin inhibitor cyclosporine A (CsA) extends the lifespan of fast-twitch skeletal muscle-specific mitochondrial transcription factor A knockout (Tfam KO) mice, lacking the ability to transcribe mitochondrial DNA and displaying lethal mitochondrial myopathy. Our present aim was to assess whether the positive effect of CsA was associated with improved in vivo mitochondrial energy production.

Comparing Different Methods for the Diagnosis of Liver Steatosis: What Are the Best Diagnostic Tools?

Background: Due to the ongoing organ shortage, marginal grafts with steatosis are more frequently used in liver transplantation, leading to higher occurrences of graft dysfunction. A histological analysis is the gold standard for the quantification of liver steatosis (LS), but has its drawbacks: it is an invasive method that varies from one pathologist to another and is not available in every hospital at the time of organ procurement. This study aimed to compare non-invasive diagnostic tools to a histological analysis for the quantification of liver steatosis.

Quantitative MRI of Gd-DOTA Accumulation in the Mouse Brain After Intraperitoneal Administration: Validation by Mass Spectrometry.

Background: In mice, intraperitoneal (ip) contrast agent (CA) administration is convenient for mapping microvascular parameters over a long-time window. However, continuous quantitative MRI of CA accumulation in brain over hours is still missing.

Purpose: To validate a quantitative time-resolved MRI technique for mapping the CA kinetics in brain upon ip administration.

Loss of Function in the His-Purkinje System Hampers Its Maturation and Leads to Mechanical Dysfunction.

The ventricular conduction or His-Purkinje system (VCS) mediates the rapid propagation and precise delivery of electrical activity essential for the synchronization of heartbeats. Mutations in the transcription factor have been implicated in a high prevalence of developing ventricular conduction defects or arrhythmias with age. heterozygous mutant mice reproduce human phenotypes associated with a hypoplastic His-Purkinje system resulting from defective patterning of the Purkinje fiber network during development.

Impaired aerobic capacity and premature fatigue preceding muscle weakness in the skeletal muscle Tfam-knockout mouse model.

Mitochondrial diseases are genetic disorders that lead to impaired mitochondrial function, resulting in exercise intolerance and muscle weakness. In patients, muscle fatigue due to defects in mitochondrial oxidative capacities commonly precedes muscle weakness. In mice, deletion of the fast-twitch skeletal muscle-specific Tfam gene (Tfam KO) leads to a deficit in respiratory chain activity, severe muscle weakness and early death.

In vivo characterization of skeletal muscle function in nebulin-deficient mice.

Introduction: The conditional nebulin knockout mouse is a new model mimicking nemaline myopathy, a rare disease characterized by muscle weakness and rods within muscle fibers. We investigated the impact of nebulin (NEB) deficiency on muscle function in vivo.

Methods: Conditional nebulin knockout mice and control littermates were studied at 10 to 12 months.

Correction: Deletion of Nkx2-5 in trabecular myocardium reveals the developmental origins of pathological heterogeneity associated with ventricular non-compaction cardiomyopathy.

[This corrects the article DOI: 10.1371/journal.pgen.

Deletion of Nkx2-5 in trabecular myocardium reveals the developmental origins of pathological heterogeneity associated with ventricular non-compaction cardiomyopathy.

Left ventricular non-compaction (LVNC) is a rare cardiomyopathy associated with a hypertrabeculated phenotype and a large spectrum of symptoms. It is still unclear whether LVNC results from a defect of ventricular trabeculae development and the mechanistic basis that underlies the varying severity of this pathology is unknown. To investigate these issues, we inactivated the cardiac transcription factor Nkx2-5 in trabecular myocardium at different stages of trabecular morphogenesis using an inducible Cx40-creERT2 allele.

Molecular basis for nucleotide conservation at the ends of the dengue virus genome.

The dengue virus (DV) is an important human pathogen from the Flavivirus genus, whose genome- and antigenome RNAs start with the strictly conserved sequence pppAG. The RNA-dependent RNA polymerase (RdRp), a product of the NS5 gene, initiates RNA synthesis de novo, i.e.

Cdk and the anillin homolog Bud4 define a new pathway regulating septin organization in yeast.

In budding yeast, the cortical structure formed by the septins is remodeled at the onset of mitotic exit and delineates a specialized compartment dedicated to cytokinesis. How this septin function is spatially and timely regulated remains poorly understood. In this study, we report a role of the anillin-like protein Bud4 in the formation and the disassembly of the double ring structure formed by the septins at the time of cytokinesis.

Compartmentalization of the functions and regulation of the mitotic cyclin Clb2 in S. cerevisiae.

Orderly progression through the eukaryotic cell cycle is a complex process involving both regulation of cyclin dependent kinase activity and control of specific substrate-Cdk interactions. In Saccharomyces cerevisiae, the mitotic cyclin Clb2 has a central role in regulating the onset of anaphase and in maintaining the cellular shape of the bud by inhibiting growth polarization induced in G1. However, how Clb2 and the partially redundant cyclin Clb1 confer specificity to Cdk1 in these processes still remains unclear.

Structural characterization of Set1 RNA recognition motifs and their role in histone H3 lysine 4 methylation.

The yeast Set1 histone H3 lysine 4 (H3K4) methyltransferase contains, in addition to its catalytic SET domain, a conserved RNA recognition motif (RRM1). We present here the crystal structure and the secondary structure assignment in solution of the Set1 RRM1. Although RRM1 has the expected betaalphabetabetaalphabeta RRM-fold, it lacks the typical RNA-binding features of these modules.

Integration of anteroposterior and dorsoventral regulation of Phox2b transcription in cranial motoneuron progenitors by homeodomain proteins.

Little is known about the molecular mechanisms that integrate anteroposterior (AP) and dorsoventral (DV) positional information in neural progenitors that specify distinct neuronal types within the vertebrate neural tube. We have previously shown that in ventral rhombomere (r)4 of Hoxb1 and Hoxb2 mutant mouse embryos, Phox2b expression is not properly maintained in the visceral motoneuron progenitor domain (pMNv), resulting in a switch to serotonergic fate. Here, we show that Phox2b is a direct target of Hoxb1 and Hoxb2.

Synthesis and biological evaluation of five-membered heterocycles fused to cyclopenta[c]thiophene as new antitumor agents.

A series of 10 derivatives 2-6 issued from the fusion of various five-membered heterocycles to cyclopenta[c]thiophene were evaluated for potential anticancer activity in the NCI's in vitro human disease-oriented tumor cell line screening panel that consisted of 60 human tumor cell lines arranged in nine subpanels, representing diverse histologies. Among these tested compounds, four were found to be cytotoxic allowing us to point out some structure-activity relationships. The oxazolidinone derivatives 2a-c displayed further in vivo antitumor activity in the hollow fiber assay and standard xenograft testing developed at the NCI.

Synthesis and biological evaluation of cyclopenta[c]thiophene related compounds as new antitumor agents.

A series of 22 cyclopenta[c]thiophene related compounds was obtained by the pharmacomodulation of 6-amino-5,6-dihydro-4H-cyclopenta[c]thiophen-4-ones 1a-g. All compounds were evaluated for potential anticancer activity in the NCI's in vitro human disease-oriented tumor cell line screening panel that consisted of 60 human tumor cell lines arranged in nine subpanels, representing diverse histologies. Among these tested compounds, seven were found to be cytotoxic, especially against leukemia cell lines, allowing us to point out some structure-activity relationships.

Involvement of mouse Rev3 in tolerance of endogenous and exogenous DNA damage.

The Rev3 gene of Saccharomyces cerevisiae encodes the catalytic subunit of DNA polymerase zeta that is implicated in mutagenic translesion synthesis of damaged DNA. To investigate the function of its mouse homologue, we have generated mouse embryonic stem cells and mice carrying a targeted disruption of Rev3. Although some strain-dependent variation was observed, Rev3(-/-) embryos died around midgestation, displaying retarded growth in the absence of consistent developmental abnormalities.