Search

Recent studies have demonstrated that Janus kinase (JAK) plays a crucial role in signal transduction by directly affecting various cytokine receptors involved in inflammatory diseases such as atopic dermatitis (AD). Large-scale clinical trials on AD utilizing JAK inhibitors and biologic reagents, such as dupilumab, which targets the IL-4Rα receptor subunit of the Th2 cytokines IL-4 and IL-13, have yielded highly favorable results in comparison to traditional therapies. This indicates that therapeutic strategies based on molecular biology are efficacious in clinical settings. However, in September 2021, the U.S. Food and Drug Administration (FDA) indicated that tofacitinib, a JAK inhibitor, may carry various risks, including severe heart disease. Similar concerns have been raised for other JAK inhibitors, and further safety evaluations are underway. Thus, human biology involving JAKs appeared more complicated than we expected. In this article, we provide an overview of the molecular mechanisms of AD and examine the molecular targeting drugs for AD from the perspective of JAK-related biology. [ABSTRACT FROM AUTHOR]

Molecular phylogenetic analyses based on mitochondrial cox1 and cox3 and chloroplast rbcL gene sequences revealed that the morphospecies of the brown alga Planosiphon gracilis (Scytosiphonaceae, Ectocarpales) from Japan is a complex of three distinct lineages (lineages I–III). Specimens from these lineages had the typical morphology of Pl. gracilis (i.e. flattened, linear, hollow, and gregarious erect thalli); thus, morphological discrimination among them was difficult in many cases. We observed large genetic divergences among the three lineages (c. 10% in cox1 and cox3). Moreover, we observed a reproductive isolating barrier between lineages I and II, despite the wide overlap in their geographic distribution. Our data, therefore, suggest that these three lineages are distinct species. Since lineage I included the holotype specimen of Pl. gracilis, this lineage was attributed to Pl. gracilis. Lineage III was phylogenetically close to Pl. complanatus from Canada with a 4.1% divergence in cox1. For lineage II, a new species name, Pl. nakamurae sp. nov., was proposed. This new species was also found in Argentina. [ABSTRACT FROM AUTHOR]

Disposition of 2-(N-acetyl-d-tyrosyl-trans-4-hydroxy-l-prolyl-l-asparaginyl-l-threonyl-l-phenylalanyl) hydrazinocarbonyl-L-leucyl-Nω-methyl-l-arginyl-l-tryptophanamide monoacetate (TAK-448, RVT-602), a synthetic kisspeptin analog, was investigated after parenteral dosing of radiolabeled TAK-448 ([d-Tyr-14C]TAK-448) to rats and dogs, and it was confirmed if the radiolabeling position at d-Tyr was eligible for assessment of in vivo disposition. Dosed radioactivity was rapidly and well absorbed after subcutaneous administration and an appreciable amount of unchanged TAK-448 (TAK-448F) and a hydrolyzed metabolite, M-I, were detected in the plasma of rats and dogs. After intravenous administration of [d-Tyr-14C]TAK-448 to rats, the radioactivity widely distributed to tissues with relatively higher concentrations in kidney and urinary bladder. The radioactivity was decreased rapidly from the tissues. After subcutaneous administration of [d-Tyr-14C]TAK-448 to rats and dogs, the dosed radioactivity was almost completely recovered by 48 and 72 h in rats and dogs, respectively, and most of the radioactivity was excreted in urine after extensive metabolism in the two species. These results suggest that TAK-448 has an acceptable pharmacokinetic profile for clinical evaluation and development, and demonstrate that the synthesized [D-Tyr-14C]TAK-448 used in this study represents a favorable labeling position to evaluate disposition properties of this compound. [ABSTRACT FROM AUTHOR]

The absorption, distribution, metabolism, and excretion of fasiglifam were investigated in rats, dogs, and humans. The absolute oral bioavailability of fasiglifam was high in all species (>76.0%). After oral administration of [14C]fasiglifam, the administered radioactivity was quantitatively recovered and the major route of excretion of radioactivity was via feces in all species. Fasiglifam was a major component in the plasma and feces in all species. Its oxidative metabolite (M-I) was observed as a minor metabolite in rat and human plasma (<10% of plasma radioactivity). In human plasma, hydroxylated fasiglifam (T-1676427), the glucuronide of fasiglifam (fasiglifam-G), and the glucuronide of M-I were detected as additional minor metabolites (<2% of plasma radioactivity). None of these metabolites were specific to humans. Fasiglifam-G was the major component in the rat and dog bile. In vitro cytochrome P450 (CYP) and uridine diphosphate glucuronosyltransferase (UGT) reaction phenotyping indicated that oxidation (to form M-I and T-1676427) and glucuronidation of fasiglifam are mainly mediated by CYP3A4/5 and UGT1A3, respectively. Fasiglifam and fasiglifam-G are substrates of BCRP and Mrp2/MRP2, respectively. Glucuronidation of fasiglifam-G was found to be the predominant elimination pathway of fasiglifam in all species tested, including humans. [ABSTRACT FROM AUTHOR]

Introduction: Drug-eluting stents (DES) are still the standard of care in percutaneous coronary intervention (PCI) since the fall of bioresorbable scaffolds with respect to safety. The unbeatable advantage of a metallic stent when compared with a scaffold is a stronger mechanical property and more sustainable vascular support. Recent development of contemporary metallic stent has focused on the reduction of strut thickness. However, there will always be a trade-off between improvement in deliverability, flexibility, and radial strength. Areas covered: This review aims to discuss the designs of metallic stent platform and mechanical properties as well as mechanical performance of contemporary DES from bench studies and clinical trials. Expert opinion: Mechanical properties of stents affect short- and long-term clinical outcomes. Ultrathin-strut DES have become popular and clinical trials have shown impressive results. Thinner struts may improve device flexibility and deliverability but the radial strength and longitudinal integrity might have been compromised as well. Ultrathin-strut cobalt chromium or platinum chromium DES will become standard of care in PCI practice in the near future. Information on the stent design, stent material and mechanical properties of the stent are essential for a rational selection of the appropriate stent in selected lesions and patients. [ABSTRACT FROM AUTHOR]

DNA-based species delimitation methods often predict many putative cryptic species. Interpretation of these putative species (i.e. do they represent distinct species, or is this an erroneous estimate based on DNA variability?) is challenging because estimates of DNA-based delimitation are often difficult to verify using nongenetic data such as morphology or geographical distribution. In the present study, estimates of DNA-based delimitation methods were verified based on the biological species concept in Japanese populations of Scytosiphon lomentaria. Three DNA-based species delimitation methods (Generalised Mixed Yule Coalescent, Poisson Tree Processes and Automatic Barcode Gap Discovery) were conducted using mitochondrial (cox1) and nuclear (second intron of centrin gene) DNA sequence datasets. In the S. lomentaria species complex, five putative cryptic species (Ia-Va) were well-supported by DNA-based species delimitation, and these putative species were often found in the same locality. To verify the estimates of DNA-based delimitation, crossing experiments were conducted among the putative species, using cultured isolates. Gametic incompatibility, which prevented hybrid zygote formation, was observed among them, except in the crosses between species IIa male and species IIIa female, in which hybrid zygotes successfully formed. These hybrid zygotes grew up to sporophytes and matured with unilocular sporangia in culture; however, the survival rate of their meiospores (zoospores) was significantly lower than that of meiospores from sporophytes derived from intraspecific crosses. In the S. lomentaria species complex in Japan, well-supported DNA-based species boundaries were concordant with biological species boundaries (intrinsic barriers to gene exchange). The five cryptic species are reproductively isolated from each other by gametic incompatibility (pre-zygotic barrier) and low survival rate of hybrid meiospores (post-zygotic barrier). [ABSTRACT FROM AUTHOR]

Among the distinctive members of the brown algal family Scytosiphonaceae is the genus Hydroclathrus, which is primarily distinguished by its clathrate (net-like) appearance. Hydroclathrus, despite being seasonal and species poor, is a conspicuous floristic component in many tropical to warm temperate coasts. However, compared with other closely related genera, such as Colpomenia and Rosenvingea, Hydroclathrus remains poorly known; its taxonomy remains problematic, as information on the molecular phylogenetic relationships of the species is still scarce. We attempted to bridge these gaps by describing the diversity and molecular phylogeny of Hydroclathrus based on morphological and genetic (mitochondrial cox1 and cox3 and plastidial psaA and rbcL genes) data. We recognised four Hydroclathrus species: H. clathratus, H. stephanosorus, H. tenuis and H. minutus sp. nov., which is morphologically cryptic to H. tenuis. A new clathrate genus, Tronoella ryukyuana gen. & sp. nov., is also erected based on specimens from southern Japan. Tronoella is primarily distinguished from Hydroclathrus in possessing (1) highly convoluted thalli with branches that are sometimes slightly twisted and/or interadhesive; (2) siphonous protrusions that grow randomly and in various directions, later on becoming perforated branches with revolute margins; and (3) plurangia that are firmly coherent and massive. Our results highlight the need to re-evaluate the identity of the species reported as H. clathratus and H. tenuis and underscore the need to re-examine the taxonomy and systematics of the family Scytosiphonaceae. [ABSTRACT FROM AUTHOR]

1. Following oral administration of [14C]TAK-438, the radioactivity was rapidly absorbed in rats and dogs. The apparent absorption of the radioactivity was high in both species. 2. After oral administration of [14C]TAK-438 to rats, the radioactivity in most tissues reached the maximum at 1-hour post-dose. By 168-hour post-dose, the concentrations of the radioactivity were at very low levels in nearly all the tissues. In addition, TAK-438F was the major component in the stomach, whereas TAK-438F was the minor component in the plasma and other tissues. High accumulation of TAK-438F in the stomach was observed after oral and intravenous administration. 3. TAK-438F was a minor component in the plasma and excreta in both species. Its oxidative metabolite (M-I) and the glucuronide of a secondary metabolite formed by non-oxidative metabolism of M-I (M-II-G) were the major components in the rat and dog plasma, respectively. The glucuronide of M-I (M-I-G) and M-II-G were the major components in the rat bile and dog urine, respectively, and most components in feces were other unidentified metabolites. 4. The administered radioactive dose was almost completely recovered. The major route of excretion of the drug-derived radioactivity was via the feces in rats and urine in dogs. [ABSTRACT FROM PUBLISHER]

Four species have been described in the genus Pikea (Dumontiaceae, Gigartinales): three species from North America and one species from Japan. However, the phylogeny and species delimitation in Pikea remain poorly resolved. Here we provide both rhcL and cox1 sequences for all species of Pikea, including the type of P. pinnata and a paratype of P. robusta. Our data reveal that P. californica, P. pinnata and P. yoshizakii are distinct in both data sets, but P. robusta is synonymous with the earlier-described P. pinnata. Morphological and molecular data show that Pikea from Korea is identical to P. yoshizakii and that the previous report of P. californica in Korea is a misidentification. The genus Pikea is well resolved in the main clade of the Dumontiaceae. This is the first study on the phylogeny of Pikea using rbcL and coxl sequence data. [ABSTRACT FROM AUTHOR]

The common brown alga Scytosiphon lomentaria (Scytosiphonaceae) has generally been regarded as a species complex. In the Pacific, molecular data have shown that it includes more than one species; the diversity in other oceans, however, has not been examined. In the present study, the genetic diversity of S. lomentaria was investigated in 57 samples from the north-east Atlantic (mainly from Ireland) and twofrom the Mediterranean, which were compared with seven samples from Japan. Phylogenetic analyses based on the mitochondrial cytochrome oxidase subunit 3 gene (cox3) and nuclear ribosomal internal transcribed spacers (ITS1 and 2) revealed four separate monophyletic groups. Clades A1 and A2 consisted of the samples from the north-east Atlantic; the Mediterranean samples also belonged to Al. The affiliation of four samples was incongruent between cox3 and ITS trees, suggesting directional mitochondrial introgression from A2 to A l . Clades PI and P2 contained nine samples from the north-east Atlantic, i.e. three Irish, all Norwegian and Icelandic samples, as well as all Pacific samples; in these clades, the cox3 and ITS data were congruent. This is the first documented record of Pacific lineages of Scytosiphon in the north-east Atlantic. Our results indicate that at least four species are passing under the name S. lomentaria in the north-east Atlantic and the Mediterranean. [ABSTRACT FROM AUTHOR]

The taxonomic distinctiveness and distribution of the brown alga Colpomenia phaeodactyla are debatable. The type locality of this species is Puerto Penasco, Mexico, and its distribution includes northeast Asia. We analyzed two gene sequences of specimens of so-called C. phaeodactyla from Korea, Japan and Mexico, in combination with morphological observations of the specimens. Analyses of 71 coxi and 23 rbcL sequences resulted in similar trees in which specimens under the name C. phaeodactyla consisted of two distinct clades. One clade comprised samples from Korea and Japan, and the other clade, from the Gulf of California, was identical to C. durvillei. Additional observations of the morphology and anatomy of the specimens agreed with the molecular data. On the basis of these results, we describe the new species C. wynnei for plants from Korea and Japan. Colpomenia wynnei was distinguished by finger-like sacs with adventitious branchlets when mature and was much contorted, the height of ascocysts being shorter than plurilocular sporangia. Both cox3 and rbcL sequence data strongly supported the monophyly of C. wynnei, C. bullosa and C. durvillei, all being characterized by having elongate thalli. Based on both cox3 and rbcL data sets, we herein propose to synonymise C. phaeodactyla with C. durvillei. [ABSTRACT FROM AUTHOR]

1. The performance of low background (BG) liquid scintillation counter (LSC) was evaluated for practical purposes of non-clinical drug absorption, distribution, metabolism and excretion (ADME) studies. The measurement conditions for the radioactivity for low BG LSC were investigated and metabolite profiling in rat plasma after single oral administration of 14C-labeled compounds was performed. Metabolite profiling was also conducted using conventional LSC and accelerator mass spectrometer (AMS), and the performances of these measuring instruments were compared. 2. The established measurement conditions showed good linearity of the calibration curve over the concentration range from 3 to 300 dpm/vial. Metabolite profiling using low BG LSC for the plasma samples diluted to 5-55 times was comparable to that using conventional LSC for the undiluted plasma samples. Meanwhile, metabolite profiling using AMS for the plasma samples diluted to 250-2000 times was comparable to that using conventional LSC. 3. These results suggest that the application of low BG LSC is one of the useful tools for non-clinical ADME studies and that it is possible to select conventional LSC, low BG LSC or AMS for radioactivity measurement by considering the specific radioactivity of the compounds and the predicted concentrations of radioactivity in biological samples in ADME studies. [ABSTRACT FROM AUTHOR]

A ceramic honeycomb was employed in a 1-kW class compact tubular fuel reformer based on noncatalytic partial oxidation (POX) of methanol. POX was stabilized on the outlet surface of the ceramic honeycomb under various experimental conditions with different equivalence ratios (φ) and thermal loads (qload); the latter represents the thermal input to the reformer calculated from the lower heating value (LHV) of methanol. The best performance of the reformer was achieved at φ = 3.5, and the adiabatic flame temperature was achieved. The location where the reaction occurred was determined, and the reaction was found to stabilize at an almost identical location under a wide range of thermal load conditions. This robust feature of the reaction is a significant characteristic of the ceramic honeycomb. By inserting a secondary honeycomb downstream of the reaction region, it was possible to move the reaction region upstream. This shifting of the reaction region was a result of the energy regeneration attributed to the adiabatic features of the honeycomb, and resulted in an improvement in reformer performance. [ABSTRACT FROM AUTHOR]

K ogame K., K urihara A., C ho G.Y., L ee K.M., S herwood A.R. and B oo S.M. 2011. sp. nov. (Scytosiphonaceae, Phaeophyceae) from the Hawaiian Islands. Phycologia 50: 563-573. DOI: 10.2216/10-75.1 A new brown alga sp. nov. (Scytosiphonaceae) is described from the Hawaiian Islands based on morphological observations and phylogenetic analyses of DNA sequences of the chloroplast-encoded rbcL gene and the ITS1-5.8S-ITS2 region of the nuclear ribosomal cistron. The thalli are linear and complanate, up to 15 cm in length and 0.8 cm in width with rhizoidal filaments in the medulla. This species is morphologically distinguishable from other species by having ascocysts among plurilocular zoidangia. Molecular phylogenetic analyses revealed that samples of form a distinct clade that is sister to the clade of (J. Agardh) Vinogradova. All our collections of Hawaiian from the main Hawaiian Islands were assigned to . [ABSTRACT FROM AUTHOR]

Sequence variations of the internal transcribed spacers (ITS) 1 and 2 of the nrDNA and the partial RuBisCO large subunit gene-spacer-partial RuBisCO small subunit gene (rbcL-sp-S) region were investigated in samples of Scytosiphon lomentaria (Lyngbye) Link from 50 localities in the Pacific (Australia, Japan, Korea, New Zealand, Russia and United States) and the North Atlantic. ITS1 and ITS2 sequences were determined for 83 samples, the rbcL-sp-S region for 43 samples, and complete rbcL sequences for two European and three Japanese samples. Molecular phylogenetic analyses using rbcL sequences were performed including S. lomentaria and 15 other scytosiphonacean species. In the rbcL analyses the S. lomentaria samples made a clade consisting of a Pacific and a European subclade. These two subclades also were supported by the ITS and rbcL-sp-S analyses. The nucleotide differences in rbcL were 1.8-2.3% (27-33 bp/1,467 bp) between the two subclades. Such differences are so large that they are considered as indicating different, although cryptic, species. In the ITS analyses the Pacific clade was further divided into two well-supported subclades. In the Pacific clade sample localities were not geographically related to the molecular phylogeny: both subclades included samples from Korea, Japan, Oregon and New Zealand. Artificial translocations are suggested to have occurred because identical sequences were found from localities far from each other, for example, Korea and the United States, the United States and New Zealand. The two Pacific groups are possibly two distinct but cryptic species. [ABSTRACT FROM AUTHOR]

The order Ralfsiales was established to accommodate the brown algal taxa having a crustose thallus, an isomorphic life history, discoid early development of the thallus and containing a single, plate-shaped chloroplast without pyrenoids in each cell. However, the validity of the order has been questioned by many researchers because several exceptions to these criteria have been found within the order. Molecular phylogenetic analysis of the taxa assigned to the order, using rbcL DNA sequences, reveals that Ralfsiales is not a monophyletic group but is separated into two major groups, excluding Lithodermataceae, which were not included in the present analysis: clade I, comprising the members of Ralfsiaceae, Mesosporaceae, A nalipus japonicus and Heteroralfsia saxicola; and clade II, consisting of Diplura species, sister to the Ishigeales clade. On the basis of these results, we propose emendment of the Ralfsiales to contain only species having (1) discoidal early development of the thallus; (2) intercalary plurilocular gametangia with terminal cells and terminal unilocular zoidangia; and (3) a crustose phase in the life history. Furthermore, we propose the establishment of the new family Neoralfsiaceae to accommodate the new genus Neoralfsia, on the basis of Ralfsia expansa. [ABSTRACT FROM AUTHOR]

The presence or absence of gamete fusion in the dioecious and isogamous brown alga Scytosiphon lomentaria (Scytosiphonaceae, Phaeophyceae) was investigated for thalli collected from three localities, Oshoro, Asari and Muroran in Hokkaido, northern Japan. Both sexual and asexual thalli were found in each locality. These sexual (35 samples) and asexual thalli (15 samples) were used to establish unialgal cultures. ITS2 sequences were determined in all cultures, the rbc L-spacer-S in 14, and cox 3 in 25 cultures. Thirteen haplotypes (A1–4, B, C1–4, D, E1–3) were found in ITS2 sequences (241–252&ThickSpace;bp). Ten haplotypes (A1–4, B, C1–4 and D) were found in sexual samples: haplotypes A and B were found in Oshoro, C and D in Asari, and C in Muroran. Haplotypes E1–3 were found in asexual samples. Sequence divergence values (including gap information) were less than 4.03% among sexual samples (A, B, C and D types), 0.38–0.77% among asexual samples (E types) and 4.39–5.70% between sexual and asexual samples. In the mitochondrial cox 3 gene region (543&ThickSpace;bp), six haplotypes (K1–3, L, M and N) were obtained. Cox 3-K types were found in samples of ITS2-A types, cox 3-L type in ITS2-B type, cox 3-M type in ITS2-C and D types, and cox 3-N type in ITS2-E types. For cox 3 sequences, nucleotide differences were 0.18–4.42% among sexual samples (K, L and M types), but 8.66–10.31% between sexual and asexual samples (N type). In partial rbc L (174&ThickSpace;bp)-spacer (188&ThickSpace;bp)-partial rbc S (90&ThickSpace;bp) sequences, six haplotypes (R–W) were found although there were 1–4&ThickSpace;bp nucleotide differences among these haplotypes. R, U and W types were found in sexual samples, and S, T and V types in asexual samples. Results of the sequence analyses suggest that our presumed asexual thalli are genetically different from sexual thalli and may be derived from populations that lack sexual reproduction. [ABSTRACT FROM AUTHOR]

Vegetative and reproductive structures, including the anatomy of young blades, spermatangia, female reproductive organs, post-fertilization development, and tetrasporangia were examined for the little-known red alga, Anatheca montagnei , from Hann Bay, Dakar, Senegal, western Africa, close to the type locality. Carpogonial branches and auxiliary cells develop on cortical filaments in slightly raised nemathecium-like structures. The fertilized carpogonium produces two unbranched, non-septate connecting filaments. The auxiliary cell is one of the intercalary cortical cells, and, together with the surrounding darkly-staining cortical cells, constitutes an auxiliary cell complex that is visible prior to diploidization. The diploidized auxiliary cell cuts off a single gonimoblast initial, which in turn divides to form a placentate cystocarp without distinct enveloping filaments. The cystocarps are contained in cystocarpic protuberances or papillae that are situated on the surfaces and margins of the female blade. Tetrasporangia are cut off laterally from their parental cells and are zonately divided. The alga is characterized by the above-mentioned combination of features but its position within the Solieriaceae was not demonstrated by our rbc L analyses. [ABSTRACT FROM AUTHOR]

A small prostrate filamentous brown alga, isolated from the warm temperate Pacific coast of Japan, was cultured to investigate its life history, morphology, ultrastructure and molecular phylogenetic position. The isolate had an isomorphic, diphasic life history with anisogamous sexual reproduction. Gametogenesis was regulated by temperature and occurred only at temperatures =14°C. At higher temperatures, gametophytes reproduced by means of asexual zoids. All swarmers from plurilocular and unilocular zoidangia lacked an eyespot. Both sporophytes and gametophytes had oligostichous filamentous axes, lateral hairs with a basal sheath and no erect thalli. Three to eight oblong chloroplasts, each with a protruding pyrenoid, aggregated to form a stellate chloroplast configuration. All these morphological features suggested that this alga belongs to the genus Asterocladon . Plurilocular gametangia produced in an intercalary or terminal position and zoids lacking eyespots, are, however, unlike those of Asterocladon lobatum , formerly the only member of the genus. Therefore, we described the alga as a new taxon, Asterocladon interjectum sp. nov. Molecular phylogenetic analyses based on the large RUBISCO subunit ( rbc L) and partial SSU nuclear ribosomal RNA gene sequences showed that A. interjectum , A. lobatum and Asteronema rhodochortonoides together formed a monophyletic clade, sister to the Ectocarpales sensu lato . Because the molecular phylogenetic analyses showed Asteronema to be paraphyletic, but monophyly of Asterocladon spp. and Asteronema rhodochortonoides was supported by the absence of cytoplasmic invaginations in pyrenoids, Asteronema rhodochortonoides was transferred to Asterocladon and an emended generic circumscription of Asterocladon was included. [ABSTRACT FROM AUTHOR]

An abstract of the article "Crossing Experiments in the Scytosiphon Lomentaria Complex (Phaeophyceae) in Japan," by K Kogame and S Ishikawa, is presented.

An abstract of the article "Differense of Elimination Timing in Male Mitochondria and Mitochondrial DNA After Fertilization Between Isogamous and Oogamous Brown Algae," by K. Kimura, K. Kogame, S. Uwai, C. Nagasato and T. Motomura, is presented.

An abstract of the article "A Phylogenetic Study of Japanese Articulated Coralline Algae (Rhodophyta)," by D. Sato, S. Shimada, K. Kogame, and M. Baba is presented.