ASP2397 Is a Novel Natural Compound That Exhibits Rapid and Potent Fungicidal Activity against Species through a Specific Transporter.

Current therapies against invasive pulmonary aspergillosis (IPA) have a limited cure rate. Given that a delay in treatment initiation may be fatal, a new drug with rapid-onset and potent fungicidal activity is needed. The novel cyclic hexapeptide ASP2397 (currently known as VL-2397) exhibited antifungal activity against (including azole-sensitive and azole-resistant isolates), , and at an MIC range of 1 to 4 μg/ml in human serum.

Mitotic chromosome assembly despite nucleosome depletion in egg extracts.

The nucleosome is the fundamental structural unit of eukaryotic chromatin. During mitosis, duplicated nucleosome fibers are organized into a pair of rod-shaped structures (chromatids) within a mitotic chromosome. However, it remains unclear whether nucleosome assembly is indeed an essential prerequisite for mitotic chromosome assembly.

The WD40 Domain of HIRA Is Essential for RI-nucleosome Assembly in Xenopus Egg Extracts.

Histone chaperones are a group of histone-binding proteins that facilitate the assembly of nucleosomes, the fundamental structural units of chromatin in eukaryotes. In nucleosome assembly, deposition of a histone H3-H4 tetramer onto DNA is the first and critical step, which is mediated by the histone chaperones HIRA and CAF-1. HIRA and CAF-1 are reportedly involved in DNA replication independent (RI) and replication coupled nucleosome assembly, respectively.

Chromatin tethering to the nuclear envelope by nuclear actin filaments: a novel role of the actin cytoskeleton in the Xenopus blastula.

The Xenopus oocyte is known to accumulate filamentous or F-actin in the nucleus, but it is currently unknown whether F-actin also accumulates in embryo nuclei. Using fluorescence-labeled actin reporters, we examined the actin distribution in Xenopus embryonic cells and found that F-actin accumulates in nuclei during the blastula stage but not during the gastrula stage. To further investigate nuclear F-actin, we devised a Xenopus egg extract that reproduces the formation of nuclei in which F-actin accumulates.

ASP2397: a novel antifungal agent produced by Acremonium persicinum MF-347833.

The novel antifungal agent ASP2397 (Vical's compound ID VL-2397) is produced by the fungal strain MF-347833 that was isolated from Malaysian leaf litter and is identified here as an Acremonium species based on its morphology, physiological properties and 28S ribosomal DNA sequence. Because of its potential importance for producing novel antifungal agents, we determined the taxonomic and biologic properties of MF-347833. We show here that ASP2397 is a cyclic hexapeptide that chelates aluminum ion and is therefore similar to ferrichrome, a hydroxamate siderophore.

Inhibitory effect of Phalaenopsis orchid extract on WNT1-induced immature melanocyte precursor differentiation in a novel in vitro solar lentigo model.

Recently, it has been reported that increased expression of WNT1 accelerates the differentiation of melanocyte stem cells (McSCs) in solar lentigines (SLs), hyperpigmented maculae commonly seen on sun-exposed areas of the skin. In this study, to establish an in vitro SL model, human epidermal squamous carcinoma cell line HSC-1, which expresses higher levels of WNT1 than normal human epidermal keratinocytes, was co-cultured with early passage normal human epidermal melanocytes (NHEMs) as an in vitro McSC model. As a result, mRNA expression levels of melanocyte differentiation-related genes MITF and TYR in NHEMs were significantly increased by co-culturing with HSC-1 cells.

Hierarchical molecular events driven by oocyte-specific factors lead to rapid and extensive reprogramming.

Nuclear transfer to oocytes is an efficient way to transcriptionally reprogram somatic nuclei, but its mechanisms remain unclear. Here, we identify a sequence of molecular events that leads to rapid transcriptional reprogramming of somatic nuclei after transplantation to Xenopus oocytes. RNA-seq analyses reveal that reprogramming by oocytes results in a selective switch in transcription toward an oocyte rather than pluripotent type, without requiring new protein synthesis.

AS2077715 is a selective inhibitor of fungal mitochondrial cytochrome bc₁ complex.

AS2077715 is a novel antifungal metabolite produced by the newly isolated fungal strain Capnodium sp. 339855. This compound has an analogous structure to funiculosin, an inhibitor of mitochondrial cytochrome bc1 complex (complex III).

Therapeutic efficacy of AS2077715 against experimental tinea pedis in guinea pigs in comparison with terbinafine.

AS2077715 is a novel antifungal metabolite produced by the newly isolated fungal strain Capnodium sp. 339855. This compound has potent inhibitory activity against Trichophyton mentagrophytes mitochondrial cytochrome bc1 complex (complex III) and potent fungicidal activity against T.

AS2077715: a novel antifungal antibiotic produced by Capnodium sp. 339855.

A novel antifungal agent, AS2077715, was isolated from the fermentation broth of a fungal strain (339855) identified as a new Capnodium species based on morphological characteristics and large-subunit ribosomal DNA sequencing. AS2077715 was isolated as a white powder via solvent extraction, HP-20 and ODS-B column chromatography and crystallization, and was determined to have the molecular formula C25H41NO7. AS2077715 has a structure related to that of funiculosin, an inhibitor of mitochondrial cytochrome bc1 complex (complex III), and showed antifungal activity against Trichophyton species.

Intranuclear DNA density affects chromosome condensation in metazoans.

Chromosome condensation is critical for accurate inheritance of genetic information. The degree of condensation, which is reflected in the size of the condensed chromosomes during mitosis, is not constant. It is differentially regulated in embryonic and somatic cells.

A closed system supports the developmental competence of human embryos after vitrification : Closed vitrification of human embryos.

Purpose: Closed-system vitrification may enable the risk of contamination to be minimised. We performed three studies to compare the developmental competence of human embryos vitrified using either a closed vitrification system (CVS; Rapid-i®) or an open vitrification system (OVS; Cryo-top®).

Methods: The first study was performed in vitro using 66 zygotes previously vitrified at pronuclear stage.

Radar-enabled recovery of the Sutter's Mill meteorite, a carbonaceous chondrite regolith breccia.

Doppler weather radar imaging enabled the rapid recovery of the Sutter's Mill meteorite after a rare 4-kiloton of TNT-equivalent asteroid impact over the foothills of the Sierra Nevada in northern California. The recovered meteorites survived a record high-speed entry of 28.6 kilometers per second from an orbit close to that of Jupiter-family comets (Tisserand's parameter = 2.

Kendrin is a novel substrate for separase involved in the licensing of centriole duplication.

The centrosome, consisting of a pair of centrioles surrounded by pericentriolar material, directs the formation of bipolar spindles during mitosis. Aberrant centrosome number can promote chromosome instability, which is implicated in tumorigenesis. Thus, centrosome duplication needs to be tightly regulated to occur only once per cell cycle.

Thyroid hormone-regulated expression of nuclear lamins correlates with dedifferentiation of intestinal epithelial cells during Xenopus laevis metamorphosis.

In the Xenopus laevis intestine during metamorphosis, which is triggered by thyroid hormone (TH), the adult epithelium develops and replaces the larval one undergoing apoptosis. We have previously shown that progenitor/stem cells of the adult epithelium originate from some differentiated larval epithelial cells. To investigate molecular mechanisms underlying larval epithelial dedifferentiation into the adult progenitor/stem cells, we here focused on nuclear lamin A (LA) and lamin LIII (LIII), whose expression is generally known to be correlated with the state of cell differentiation.

Bioconversion of AS1387392: bioconversion studies involving Amycolatopsis azurea JCM 3275.

We screened actinomycetes capable of converting AS1387392 to AS1429716 and identified those strains capable of hydroxylation. Amycolatopsis azurea JCM 3275 was found to be a particularly efficient strain, capable of converting AS1387392 to AS1429716, with a yield of 44% after 9 h. This strain can metabolize not only the hydroxylation of phenylalanine at the meta and para positions but also the reduction of hydroxyketones, as shown by the isolation of bioconversion products.

Oocyte-type linker histone B4 is required for transdifferentiation of somatic cells in vivo.

The ability to reprogram in vivo a somatic cell after differentiation is quite limited. One of the most impressive examples of such a process is transdifferentiation of pigmented epithelial cells (PECs) to lens cells during lens regeneration in newts. However, very little is known of the molecular events that allow newt cells to transdifferentiate.

Transient activation of calcineurin is essential to initiate embryonic development in Xenopus laevis.

At fertilization, an increase of cytosolic calcium ions (Ca2+) triggers various activation responses in animal eggs. In vertebrates, these responses include exit from metaphase arrest in meiosis II (MII exit) and cortical remodelling initiated by cortical granule exocytosis. Although the essential requirement of Ca2+/calmodulin-dependent protein kinase II for inducing MII exit has been documented, a role of the Ca2+/calmodulin-dependent protein phosphatase calcineurin in egg activation has not been investigated.

Proteomic analysis of immature murine melanocytes at different stages of maturation: a crucial role for calreticulin.

Background: We have established two immature melanocyte cell lines from murine neural crest cells. NCC-E3 cells have Stage II melanosomes and express tyrosinase while in NCCmelb4 cells, the melanosomes remain at Stage I and tyrosinase is not expressed. These cell lines may be useful in studying the differentiation of melanocyte precursors.

Reprogramming events of mammalian somatic cells induced by Xenopus laevis egg extracts.

It is known that differentiated cells can be reprogrammed to an undifferentiated state in oocyte cytoplasm after nuclear transfer. Recently, some reports suggested that Xenopus egg extracts have the ability to reprogram mammalian somatic cells. Reprogramming events of mammalian cells after Xenopus egg extract treatment and after cell culture of extract-treated cells have not been elucidated.

Synthesis and evaluation of isoxazole derivatives as lysophosphatidic acid (LPA) antagonists.

A series of isoxazole derivatives were synthesized and their antagonistic activities against LPA stimulation on both LPA(1)/CHO cells and rHSC cells were evaluated. Among them, 3-(4-[4-[1-(2-chloro-cyclopent-1-enyl)-ethoxycarbonylamino]-isoxazol-3- y]]-benzylsulfanyl)-propionic acid (34) showed the most potent activities.

Phosphorylation of Erp1 by p90rsk is required for cytostatic factor arrest in Xenopus laevis eggs.

Until fertilization, the meiotic cell cycle of vertebrate eggs is arrested at metaphase of meiosis II by a cytoplasmic activity termed cytostatic factor (CSF), which causes inhibition of the anaphase-promoting complex/cyclosome (APC/C), a ubiquitin ligase that targets mitotic cyclins-regulatory proteins of meiosis and mitosis-for degradation. Recent studies indicate that Erp1/Emi2, an inhibitor protein for the APC/C, has an essential role in establishing and maintaining CSF arrest, but its relationship to Mos, a mitogen-activated protein kinase (MAPK) kinase kinase that also has an essential role in establishing CSF arrest through activation of p90 ribosomal S6 kinase (p90rsk), is unclear. Here we report that in Xenopus eggs Erp1 is a substrate of p90rsk, and that Mos-dependent phosphorylation of Erp1 by p90rsk at Thr 336, Ser 342 and Ser 344 is crucial for both stabilizing Erp1 and establishing CSF arrest in meiosis II oocytes.