Cardiac Reprogramming and Gata4 Overexpression Reduce Fibrosis and Improve Diastolic Dysfunction in Heart Failure With Preserved Ejection Fraction.

Background: Heart failure with preserved ejection fraction (HFpEF) is a major health concern. Pathological stimuli and interactions between cardiac fibroblasts (CFs) and other cell types may lead to cardiac fibrosis and diastolic dysfunction, which are hallmarks of HFpEF. Interstitial and perivascular cardiac fibrosis correlates with poor prognosis in HFpEF; however, mechanisms of fibrosis remain poorly elucidated, and targeted therapies are lacking.

Drosophila Piwi distinguishes transposons from mRNAs by piRNA complementarity and abundance.

Piwi-interacting RNAs (piRNAs) are the main repressors of transposable elements (TEs) in animal germlines. In Drosophila, Piwi-piRNA complexes associate with nascent TE transcripts to drive heterochromatin formation and TE repression. However, previous studies have shown that Piwi also associates with large numbers of mRNAs, raising the question of how Piwi discriminates between mRNAs and TEs.

A SARS-CoV-2 recombinant spike protein vaccine (S-268019-b) for COVID-19 prevention during the Omicron-dominant period: A phase 3, randomised, placebo-controlled clinical trial.

Clinical trials of new vaccines based on existing variants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are often impacted by the emergence of new virus variants. We evaluated the efficacy, immunogenicity, and safety of S-268019-b, a recombinant spike protein subunit vaccine based on the ancestral strain, for preventing symptomatic coronavirus disease 2019 (COVID-19) during the Omicron (BA.2)-dominant period in Vietnam.

PIGB maintains nuclear lamina organization in skeletal muscle of Drosophila.

The nuclear lamina (NL) plays various roles and participates in nuclear integrity, chromatin organization, and transcriptional regulation. Lamin proteins, the main components of the NL, form a homogeneous meshwork structure under the nuclear envelope. Lamins are essential, but it is unknown whether their homogeneous distribution is important for nuclear function.

Mod(mdg4) variants repress telomeric retrotransposon HeT-A by blocking subtelomeric enhancers.

Telomeres in Drosophila are composed of sequential non-LTR retrotransposons HeT-A, TART and TAHRE. Although they are repressed by the PIWI-piRNA pathway or heterochromatin in the germline, the regulation of these retrotransposons in somatic cells is poorly understood. In this study, we demonstrated that specific splice variants of Mod(mdg4) repress HeT-A by blocking subtelomeric enhancers in ovarian somatic cells.

Bioluminescence Resonance Energy Transfer for Global DNA Methylation Quantification.

Global hypomethylation of genomic DNA is associated with genomic instability and carcinogenic processes. The loss of DNA methylation has been reported in several cancers; therefore, global methylation levels have been considered as biomarkers for cancer diagnosis. Bisulfite conversion analysis has been widely used as the gold standard method for quantification of DNA methylation levels.

Siwi cooperates with Par-1 kinase to resolve the autoinhibitory effect of Papi for Siwi-piRISC biogenesis.

Bombyx Papi acts as a scaffold for Siwi-piRISC biogenesis on the mitochondrial surface. Papi binds first to Siwi via the Tudor domain and subsequently to piRNA precursors loaded onto Siwi via the K-homology (KH) domains. This second action depends on phosphorylation of Papi.

Maelstrom functions in the production of Siwi-piRISC capable of regulating transposons in germ cells.

PIWI-interacting RNAs (piRNAs) bind to PIWI proteins to assemble the piRISC, which represses germline transposons. Maelstrom (Mael) is necessary for piRISC biogenesis in germ cells, but its function remains unclear. Here, we show that Mael interconnects Spindle-E (Spn-E), a key piRISC biogenesis factor, with unloaded Siwi, one of two silkworm PIWI members.

Destabilization of DNA and RNA G-quadruplex structures formed by GGA repeat due to N-methyladenine modification.

N-methyladenine (mA) is the most abundant RNA modification in eukaryotic RNA. Further, mA has been identified in the genomic DNA of both eukaryotes and prokaryotes. The G-quadruplex (G4) structure is a non-canonical nucleic acid structure formed by the stacking of G:G:G:G tetrads.

Pro108Ser mutation of SARS-CoV-2 3CL reduces the enzyme activity and ameliorates the clinical severity of COVID-19.

Recently, an international randomized controlled clinical trial showed that patients with SARS-CoV-2 infection treated orally with the 3-chymotrypsin-like protease (3CL) inhibitor PF-07321332 within three days of symptom onset showed an 89% lower risk of COVID-19-related hospital admission/ death from any cause as compared with the patients who received placebo. Lending support to this critically important result of the aforementioned trial, we demonstrated in our study that patients infected with a SARS-Cov-2 sub-lineage (B.1.

Randomized Trial of Perfusion-Based Circulatory Management in Infants of Very Low Birth Weight.

Objective: To establish the superiority of blood flow (BF)-based circulatory management over conventional blood pressure (BP)-based management strategies used for preventing intraventricular hemorrhage (IVH) in infants of very low birth weight (VLBW).

Study Design: We conducted a nonblinded, single-centered randomized trial with the aim to prevent IVH by managing BF. Infants with VLBW were assigned randomly to a BF-based group or BP-based (BP group) circulatory management group.

Clinical Utility of SARS-CoV-2 Whole Genome Sequencing in Deciphering Source of Infection.

COVID-19 caused by SARS-CoV-2 is a worldwide problem. From the standpoint of hospital infection control, determining the source of infection is critical. We conducted the present study to evaluate the efficacy of using whole genome sequencing to determine the source of infection in hospitalized patients who do not have a clear infectious contact history.

Production of functional oocytes requires maternally expressed PIWI genes and piRNAs in golden hamsters.

Many animals have a conserved adaptive genome defence system known as the Piwi-interacting RNA (piRNA) pathway, which is essential for germ cell development and function. Disruption of individual mouse Piwi genes results in male but not female sterility, leading to the assumption that PIWI genes play little or no role in mammalian oocytes. Here, we report the generation of PIWI-defective golden hamsters, which have defects in the production of functional oocytes.

Piwi-piRNA complexes induce stepwise changes in nuclear architecture at target loci.

PIWI-interacting RNAs (piRNAs) are germline-specific small RNAs that form effector complexes with PIWI proteins (Piwi-piRNA complexes) and play critical roles for preserving genomic integrity by repressing transposable elements (TEs). Drosophila Piwi transcriptionally silences specific targets through heterochromatin formation and increases histone H3K9 methylation (H3K9me3) and histone H1 deposition at these loci, with nuclear RNA export factor variant Nxf2 serving as a co-factor. Using ChEP and DamID-seq, we now uncover a Piwi/Nxf2-dependent target association with nuclear lamins.

Identification of B.1.346 Lineage of SARS-CoV-2 in Japan: Genomic Evidence of Re-entry of Clade 20C.

SARS-CoV-2 whole-genome sequencing of samples from COVID-19 patients is useful for informing infection control. Datasets of these genomes assembled from multiple hospitals can give critical clues to regional or national trends in infection. Herein, we report a lineage summary based on data collected from hospitals located in the Tokyo metropolitan area.

Neonatal systemic juvenile Xanthogranuloma with Hydrops diagnosed by Purpura skin biopsy: a case report and literature review.

Background: Systemic juvenile xanthogranuloma is a very rare disease typically presents as skin lesions with yellow papules or nodules and is sometimes fatal. We report a case of congenital neonatal systemic juvenile xanthogranuloma with atypical skin appearance that made the diagnosis difficult.

Case Presentation: A preterm Japanese female neonate with prenatally diagnosed fetal hydrops in-utero was born with purpuric lesions involving the trunk and face.

Hamster PIWI proteins bind to piRNAs with stage-specific size variations during oocyte maturation.

In animal gonads, transposable elements are actively repressed to preserve genome integrity through the PIWI-interacting RNA (piRNA) pathway. In mice, piRNAs are abundantly expressed in male germ cells, and form effector complexes with three distinct PIWIs. The depletion of individual Piwi genes causes male-specific sterility with no discernible phenotype in female mice.

Identification of candidate molecular targets of the novel antineoplastic antimitotic NP-10.

We previously reported the identification of a novel antimitotic agent with carbazole and benzohydrazide structures: N'-[(9-ethyl-9H-carbazol-3-yl)methylene]-2-iodobenzohydrazide (code number NP-10). However, the mechanism(s) underlying the cancer cell-selective inhibition of mitotic progression by NP-10 remains unclear. Here, we identified NP-10-interacting proteins by affinity purification from HeLa cell lysates using NP-10-immobilized beads followed by mass spectrometry.

Nuclear RNA export factor variant initiates piRNA-guided co-transcriptional silencing.

The PIWI-interacting RNA (piRNA) pathway preserves genomic integrity by repressing transposable elements (TEs) in animal germ cells. Among PIWI-clade proteins in Drosophila, Piwi transcriptionally silences its targets through interactions with cofactors, including Panoramix (Panx) and forms heterochromatin characterized by H3K9me3 and H1. Here, we identified Nxf2, a nuclear RNA export factor (NXF) variant, as a protein that forms complexes with Piwi, Panx, and p15.

Tbx6 Induces Nascent Mesoderm from Pluripotent Stem Cells and Temporally Controls Cardiac versus Somite Lineage Diversification.

The mesoderm arises from pluripotent epiblasts and differentiates into multiple lineages; however, the underlying molecular mechanisms are unclear. Tbx6 is enriched in the paraxial mesoderm and is implicated in somite formation, but its function in other mesoderms remains elusive. Here, using direct reprogramming-based screening, single-cell RNA-seq in mouse embryos, and directed cardiac differentiation in pluripotent stem cells (PSCs), we demonstrated that Tbx6 induces nascent mesoderm from PSCs and determines cardiovascular and somite lineage specification via its temporal expression.

Hierarchical roles of mitochondrial Papi and Zucchini in Bombyx germline piRNA biogenesis.

PIWI-interacting RNAs (piRNAs) are small regulatory RNAs that bind to PIWI proteins to control transposons and maintain genome integrity in animal germ lines. piRNA 3' end formation in the silkworm Bombyx mori has been shown to be mediated by the 3'-to-5' exonuclease Trimmer (Trim; known as PNLDC1 in mammals), and piRNA intermediates are bound with PIWI anchored onto mitochondrial Tudor domain protein Papi. However, it remains unclear whether the Zucchini (Zuc) endonuclease and Nibbler (Nbr) 3'-to-5' exonuclease, both of which have pivotal roles in piRNA biogenesis in Drosophila, are required for piRNA processing in other species.

A Case of Fatal Pulmonary Hypoplasia with Congenital Diaphragmatic Hernia, Thoracic Myelomeningocele, and Thoracic Dysplasia.

 Congenital diaphragmatic hernia (CDH) is fatal in severe cases of pulmonary hypoplasia. We experienced a fatal case of pulmonary hypoplasia due to CDH, thoracic myelomeningocele (MMC), and thoracic dysplasia. This constellation of anomalies has not been previously reported.