Diagnosis of Leptomeningeal Disease in Diffuse Midline Gliomas by Detection of H3F3A K27M Mutation in Circulating Tumor DNA of Cerebrospinal Fluid.

Introduction: Leptomeningeal disease (LMD) in diffuse midline gliomas (DMGs) can lead to devastating symptoms such as severe pain, urinary incontinence, and tetraparesis, with limited treatment options. We determined whether detecting H3F3A K27M-mutant droplets in cerebrospinal fluid (CSF) circulating tumor deoxyribonucleic acid (ctDNA) could be a biomarker for detecting LMD in DMGs.

Methods: Twenty-five CSF samples were obtained from 22 DMG patients.

Ultrastructural expansion microscopy (U-ExM) visualization of malaria parasite dense granules using RESA as a representative marker protein.

Dense granules (DG) are understudied apical organelles in merozoites, the malaria parasite stage that invades erythrocytes. Only six proteins have been identified which localize to DGs, despite that DG proteins play crucial roles in multiple steps of intraerythrocytic parasite development. To develop a tool for investigating DG structure and function, this study applied ultrastructural expansion microscopy (U-ExM) to visualize the ring-infected erythrocyte surface antigen (RESA) in Plasmodium falciparum merozoites.

Simultaneous Detection of Multiple Analytes at Ambient Temperature Using Eukaryotic Artificial Cells with Modular and Robust Synthetic Riboswitches.

Cell-free systems, which can express an easily detectable output (protein) with a DNA or mRNA template, are promising as foundations of biosensors devoid of cellular constraints. Moreover, by encasing them in membranes such as natural cells to create artificial cells, these systems can avoid the adverse effects of environmental inhibitory molecules. However, the bacterial systems generally used for this purpose do not function well at ambient temperatures.

Histone Modification-Dependent Transcriptional Regulation of Defence Genes in Early Response of Arabidopsis to Spodoptera litura Attack.

Histone modification is a cellular process for transcriptional regulation. In herbivore-damaged plants, activation of genes involved in defence responses is required for antiherbivore properties, but little is known about how the chromatin remodelling system is involved. In Arabidopsis (Arabidopsis thaliana) plants responding to Spodoptera litura larvae, HAC1 and HDA6, a histone acetyltransferase and a histone deacetylase, respectively, were found here to be involved in histone H3 (Lys9; H3K9) acetylation/deacetylation at the promoter region of the plant defensin gene PDF1.

A sensitive ERK fluorescent probe reveals the significance of minimal EGF-induced transcription.

Extracellular signal-regulated kinase (ERK) regulates multiple cellular functions through distinct activation patterns. Genetically encoded fluorescent probes are instrumental in dissecting the ERK activity dynamics in living cells. Here we modified a previously reported Förster resonance energy transfer (FRET) probe for ERK, EKAREN5 by replacing its mTurquoise2 and YPet sequences with mTurquoise-GL and a synonymous codon variant of YPet, respectively.

Cell-type specific, inducible and acute degradation of targeted protein in mice by two degron systems.

Despite its broad application in in vitro studies, the application of targeted protein degradation (TPD) to animal models faces considerable challenges. Here, we develop inducible and cell-type specific TPD systems in mice using two degron systems: Oryza sativa TIR1 (OsTIR1)-auxin-inducible degron 2 (AID2) and human cereblon (hCRBN)-SALL4 degron (S4D). Efficient degradation of Satb1 protein by these systems recapitulates phenotypes observed in the Satb1-deficient mice.

BMP3b regulates bone mass by inhibiting BMP signaling.

Bone morphogenetic protein 3b (BMP3b), also known as growth differentiation factor 10 (GDF10), is a non-osteogenic BMP highly expressed in the skeleton. Although in vitro studies have shown that BMP3b suppresses osteoblast differentiation, the physiological role of BMP3b in regulating bone mass in vivo remains unknown. Here, we show that BMP3b deletion in mice leads to a high bone mass phenotype via an unexpected novel mechanism involving de-repression of canonical BMP/Smad signaling.

Intricate intracellular kinase network regulates the Spodoptera lituta-derived elicitor response signaling in Arabidopsis.

Plants defend themselves against herbivores by recognizing herbivore-derived elicitors and activating intracellular signaling. In Arabidopsis, the receptor-like kinase HAK1 recognizes the poly-saccharide elicitor (FrA) from Spodoptera litura larvae, leading to the expression of defense-related genes such as PDF1.2.

RH5: rationally-designed malaria vaccine antigen improving efficacy.

Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) is a unique asexual blood-stage malaria vaccine candidate because of its high conservation and essential biological function of binding to basigin on the erythrocyte surface. Recent studies by Barrett et al., Wang et al.

A systems serology approach to identifying key antibody correlates of protection from cerebral malaria in Malawian children.

Background: Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) proteins are expressed on the surface of infected erythrocytes, mediating parasite sequestration in the vasculature. PfEMP1 is a major target of protective antibodies, but the features of the antibody response are poorly defined.

Methods: In Malawian children with cerebral or uncomplicated malaria, we characterized the antibody response to 39 recombinant PfEMP1 Duffy binding like (DBL) domains or cysteine-rich interdomain regions (CIDRs) in detail, including measures of antibody classes, subclasses, and engagement with Fcγ receptors and complement.

A chemical approach to extend flower longevity of Japanese morning glory via inhibition of master senescence regulator EPHEMERAL1.

Petal senescence in flowering plants is a type of programmed cell death with highly regulated onset and progression. A NAM/ATAF1,2/CUC2 transcription factor, EPHEMERAL1 (EPH1), has been identified as a key regulator of petal senescence in Japanese morning glory (Ipomoea nil). Here we used a novel chemical approach to delay petal senescence in Japanese morning glory by inhibiting the DNA-binding activity of EPH1.

Direct Binding of Synaptopodin 2-Like Protein to Alpha-Actinin Contributes to Actin Bundle Formation in Cardiomyocytes.

Synaptopodin 2-like protein (SYNPO2L) is localized in the sarcomere of cardiomyocytes and is involved in heart morphogenesis. However, the molecular function of SYNPO2L in the heart is not fully understood. We investigated the interaction of SYNPO2L with sarcomeric α-actinin and actin filaments in cultured mouse cardiomyocytes.

Naked mole-rat TMEM2 lacks physiological hyaluronan-degrading activity.

Mouse transmembrane protein 2 (mTMEM2) has been identified as a hyaluronidase, which has extracellularly G8 and GG domains and PbH1 repeats; however, our previously study showed that human TMEM2 (hTMEM2) is not a catalytic hyaluronidase due to the absence of the critical amino acid residues (His248/Ala303) in the GG domain. Naked mole-rats (NMRs) accumulate abundant high-molecular weight hyaluronan (HA) in their tissues, suggesting decreased HA degradation. Therefore, we aimed to evaluate the HA-degrading activity of NMR TMEM2 (nmrTMEM2) and compare it with those of mTMEM2 and hTMEM2.

KIF22 regulates mitosis and proliferation of chondrocyte cells.

Point mutations in have been linked to spondyloepimetaphyseal dysplasia with joint laxity, type 2 (SEMDJL2). Skeletal features of SEMDJL2 include short stature and joint laxity. Mechanisms underlying these limb abnormalities are unknown.

Schlafen 11 further sensitizes BRCA-deficient cells to PARP inhibitors through single-strand DNA gap accumulation behind replication forks.

The preferential response to PARP inhibitors (PARPis) in BRCA-deficient and Schlafen 11 (SLFN11)-expressing ovarian cancers has been documented, yet the underlying molecular mechanisms remain unclear. As the accumulation of single-strand DNA (ssDNA) gaps behind replication forks is key for the lethality effect of PARPis, we investigated the combined effects of SLFN11 expression and BRCA deficiency on PARPi sensitivity and ssDNA gap formation in human cancer cells. PARPis increased chromatin-bound RPA2 and ssDNA gaps in SLFN11-expressing cells and even more in cells with BRCA1 or BRCA2 deficiency.

Crystal structure of L-2-keto-3-deoxyfuconate 4-dehydrogenase reveals a unique binding mode as a α-furanosyl hemiketal of substrates.

L-2-Keto-3-deoxyfuconate 4-dehydrogenase (L-KDFDH) catalyzes the NAD-dependent oxidization of L-2-keto-3-deoxyfuconate (L-KDF) to L-2,4-diketo-3-deoxyfuconate (L-2,4-DKDF) in the non-phosphorylating L-fucose pathway from bacteria, and its substrate was previously considered to be the acyclic α-keto form of L-KDF. On the other hand, BDH2, a mammalian homolog with L-KDFDH, functions as a dehydrogenase for cis-4-hydroxy-L-proline (C4LHyp) with the cyclic structure. We found that L-KDFDH and BDH2 utilize C4LHyp and L-KDF, respectively.

Cell-Free Biosensors Based on Modular Eukaryotic Riboswitches That Function in One Pot at Ambient Temperature.

Artificial riboswitches responsive to user-defined analytes can be constructed by successfully inserting selected aptamers, which bind to the analytes, into untranslated regions of mRNA. Among them, eukaryotic riboswitches are more promising as biosensors than bacterial ones because they function well at ambient temperature. In addition, cell-free expression systems allow the broader use of these riboswitches as cell-free biosensors in an environmentally friendly manner without cellular limitations.

Autoantibodies inhibit Plasmodium falciparum growth and are associated with protection from clinical malaria.

Many infections, including malaria, are associated with an increase in autoantibodies (AAbs). Prior studies have reported an association between genetic markers of susceptibility to autoimmune disease and resistance to malaria, but the underlying mechanisms are unclear. Here, we performed a longitudinal study of children and adults (n = 602) in Mali and found that high levels of plasma AAbs before the malaria season independently predicted a reduced risk of clinical malaria in children during the ensuing malaria season.

Rhodium-catalyzed homo-coupling reaction of aryl Grignard reagents and its application for the synthesis of an integrin inhibitor.

A novel Rh-catalyzed one-pot homo-coupling reaction of aryl Grignard reagents was achieved. The reaction with bromobenzenes having an electron-donating group or a halogen substituent gave the corresponding homo-coupling products in good yields, although the reaction using heterocyclic or aliphatic bromides scarcely proceeded. A Rh(III)-bis(aryl) complex, which might be formed from RhCl(PPh) and the aryl Grignard reagents, plays an important role in giving the homo-coupling products in this reaction.

CANE, a Component of the NLRP3 Inflammasome, Promotes Inflammasome Activation.

The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3, also called cryopyrin) inflammasome is an intracellular innate immune complex, which consists of the pattern-recognition receptor NLRP3, the adaptor apoptosis-assciated speck-like protein containing a caspase recruitment domain, and procaspase-1. Aberrant activation of the NLRP3 inflammasome causes an autoinflammatory disease called cryopyrin-associated periodic syndrome (CAPS). CAPS is caused by gain-of-function mutations in the NLRP3-encoding gene CIAS1; however, the mechanism of CAPS pathogenesis has not been fully understood.