Eradication of the mongoose is crucial for the conservation of three endemic bird species in Yambaru,Okinawa Island,Japan

Okinawa Island, Japan, is a globally important biodiversity hotspot. Three endemic bird species, Okinawa rail (Hypotaenidia okinawae), Okinawa woodpecker (Dendrocopos noguchii), and Okinawa robin (Larvivora namiyei), are found only in the Yambaru region of the northern part of Okinawa Island. In order to conserve endemic species, it is important to determine the effect of alien species on endemic species. We conducted playback surveys four times every three years from 2007 to 2016 to evaluate the recent distribution of these three forest-dwelling bird species during the breeding season. Then, the association between the numbers of detections of these three species with the invasive mongoose density and the hardwood forest area was evaluated with a generalized additive mixed model (GAMM). The results showed that the distribution areas of these bird species have been recovering since the 2007 within the small Indian mongoose (Urva auropunctata) controlled area. The GAMM results showed that these bird species were abundant in areas with fewer small Indian mongooses and larger areas of hardwood forests. Thus, the mongoose had a negative impact not only on the flightless rails but also on the woodpeckers and the robins. In recent years, most of the old-growth forests have been designated as protected forests, and large-scale logging is no longer taking place in Yambaru. Eradication of the mongoose is particularly important for the conservation of these three endemic bird species.

     

The clinical significance of 5% change in vital capacity in patients with idiopathic pulmonary fibrosis: extended analysis of the pirfenidone trial

Background

The rate of decline in forced expiratory volume in 1 second (FEV₁) is representative of the natural history of COPD. Sparse information exists regarding the associations between the magnitude of annualised loss of FEV₁ with other endpoints.

Methods

Retrospective analysis of UPLIFT^® trial (four-year, randomized, double-blind, placebo-controlled trial of tiotropium 18 μg daily in chronic obstructive pulmonary disease [COPD], n = 5993). Decline of FEV₁ was analysed with random co-efficient regression. Patients were categorised according to quartiles based on the rate of decline (RoD) in post-bronchodilator FEV_1. The St George's Respiratory Questionnaire (SGRQ) total score, exacerbations and mortality were assessed within each quartile.

Results

Mean (standard error [SE]) post-bronchodilator FEV₁ increased in the first quartile (Q1) by 37 (1) mL/year. The other quartiles showed annualised declines in FEV₁ (mL/year) as follows: Q2 = 24 (1), Q3 = 59 (1) and Q4 = 125 (2). Age, gender, respiratory medication use at baseline and SGRQ did not distinguish groups. The patient subgroup with the largest RoD had less severe lung disease at baseline and contained a higher proportion of current smokers. The percentage of patients with ≥ 1 exacerbation showed a minimal difference from the lowest to the largest RoD, but exacerbation rates increased with increasing RoD. The highest proportion of patients with ≥ 1 hospitalised exacerbation was in Q4 (Q1 = 19.5% [tiotropium], 26% [control]; Q4 = 33.8% [tiotropium] and 33.1% [control]). Time to first exacerbation and hospitalised exacerbation was shorter with increasing RoD. Rate of decline in SGRQ increased in direct proportion to each quartile. The group with the largest RoD had the highest mortality.

Conclusion

Patients can be grouped into different RoD quartiles with the observation of different clinical outcomes indicating that specific (or more aggressive) approaches to management may be needed.

Trial Registration

ClinicalTrials.gov number, NCT00144339     

Time-lapse imaging reveals symmetric neurogenic cell division of GFAP-expressing progenitors for expansion of postnatal dentate granule neurons

Granule cells in the hippocampus, a region critical for memory and learning, are generated mainly during the early postnatal period but neurogenesis continues in adulthood. Postnatal neuronal production is carried out by primary progenitors that express glial fibrillary acidic protein (GFAP) and they are assumed to function as stem cells. A central question regarding postnatal dentate neurogenesis is how astrocyte-like progenitors produce neurons. To reveal cell division patterns and the process of neuronal differentiation of astrocyte-like neural progenitors, we performed time-lapse imaging in cultured hippocampal slices from early postnatal transgenic mice with mouse GFAP promoter-controlled enhanced green fluorescent protein (mGFAP-eGFP Tg mice) in combination with a retrovirus carrying a red fluorescent protein gene. Our results showed that the majority of GFAP-eGFP+ progenitor cells that express GFAP, Sox2 and nestin divided symmetrically to produce pairs of GFAP+ cells (45%) or pairs of neuron-committed cells (45%), whereas a minority divided asymmetrically to generate GFAP+ cells and neuron-committed cells (10%). The present results suggest that a substantial number of GFAP-expressing progenitors functions as transient amplifying progenitors, at least in an early postnatal dentate gyrus, although a small population appears to be stem cell-like progenitors. From the present data, we discuss possible cell division patterns of adult GFAP+ progenitors.     

Isolation and characterization of human trophoblast side-population (SP) cells in primary villous cytotrophoblasts and HTR-8/SVneo cell line

Recently, numerous studies have identified that immature cell populations including stem cells and progenitor cells can be found among "side-population" (SP) cells. Although SP cells isolated from some adult tissues have been reported elsewhere, isolation and characterization of human trophoblast SP remained to be reported. In this study, HTR-8/SVneo cells and human primary villous cytotrophoblasts (vCTBs) were stained with Hoechst 33342 and SP and non-SP (NSP) fractions were isolated using a cell sorter. A small population of SP cells was identified in HTR-8/SVneo cells and in vCTBs. SP cells expressed several vCTB-specific markers and failed to express syncytiotrophoblast (STB) or extravillous cytotrophopblast (EVT)-specific differentiation markers. SP cells formed colonies and proliferated on mouse embryonic fibroblast (MEF) feeder cells or in MEF conditioned medium supplemented with heparin/FGF2, and they also showed long-term repopulating property. SP cells could differentiate into both STB and EVT cell lineages and expressed several differentiation markers. Microarray analysis revealed that IL7R and IL1R2 were exclusively expressed in SP cells and not in NSP cells. vCTB cells sorted as positive for both IL7R and IL1R2 failed to express trophoblast differentiation markers and spontaneously differentiated into both STB and EVT in basal medium. These features shown by the SP cells suggested that IL7R and IL1R2 are available as markers to detect the SP cells and that vCTB progenitor cells and trophoblast stem cells were involved in the SP cell population.     

Functional role of a putative carbonic anhydrase II-binding domain in the electrogenic Na+ -HCO₃- cotransporter NBCe1 expressed in Xenopus oocytes

The electrogenic Na+ -HCO?? cotransporter NBCe1 plays essential roles in the regulation of systemic and/or local pH. Homozygous inactivating mutations in NBCe1 cause proximal renal tubular acidosis associated with ocular abnormalities. We recently showed that defective membrane expression of NBCe1, caused by several mutations such as Delta65bp (S982NfsX4), is also associated with familial migraine. The Delta65bp mutant is quite unique in that it lacks a putative carbonic anhydrase (CA) II-binding domain but still shows an apparently normal transport activity in Xenopus oocytes. In this addendum, we show that the co-expression of CAII together with the wild-type NBCe1 or the Delta65bp mutant does not enhance the NBCe1 activities in oocytes. Moreover, a carbonic anhydrase inhibitor acetazolamide fails to inhibit the wild-type or the Delta65bp activities co-expressed with CAII. These results indicate that a bicarbonate transport metabolon proposed for the interaction between CAII and NBCe1 does not work at least in Xenopus oocytes.     

How does acyl chain length affect thermotropic phase behavior of saturated diacylphosphatidylcholine–cholesterol binary bilayers?

Thermotropic phase behavior of diacylphosphatidylcholine (CnPC)–cholesterol binary bilayers (n = 14–16) was examined by fluorescence spectroscopy using 6-propionyl-2-(dimethylamino)naphthalene (Prodan) and differential scanning calorimetry. The former technique can detect structural changes of the bilayer in response to the changes in polarity around Prodan molecules partitioned in a relatively hydrophilic region of the bilayer, while the latter is sensitive to the conformational changes of the acyl chains. On the basis of the data from both techniques, we propose possible temperature T–cholesterol composition X_ch phase diagrams for these binary bilayers. A notable feature of our phase diagrams, including our previous results for diheptadecanoylphosphatidylcholine (C17PC) and distearoylphosphatidylcholine (C18PC), is that there is a peritectic-like point around X_ch = 0.15, which can be interpreted as indicating the formation of a 1:6-complex of cholesterol and CnPCs within the binary bilayer irrespective of the acyl chain length. We could give a reasonable explanation for such complex formation using the modified superlattice view. Our results also showed that the X_ch value of the abolition of the main transition is almost constant for n = 14–17 (ca. 0.33), while it increases to ca. 0.50 for n = 18. By contrast, a biphasic n-dependence of X_ch was observed for the abolition of the pretransition, suggesting that there are at least two antagonistic n-dependent factors. We speculate that this could be explained by the enhancement of the van der Waals interaction with increases in n and the weakening of the repulsion between the neighboring headgroups with decreases in n.     

Neonicotinoid resistance and cDNA sequences of nicotinic acetylcholine receptor subunits of the western flower thrips Frankliniella occidentalis (Thysanoptera: Thripidae)

The western flower thrips, Frankliniella occidentalis (Pergande), is difficult to control because of high insecticide resistance. In this study, susceptibility to major insecticides was examined in two Japanese strains (H-1 and KC) and a Chinese strain (BJ) using a leaf-dipping method. All three strains were resistant to permethrin and acetamiprid at agriculturally recommended doses. The median lethal concentration (LC₅₀) for acetamiprid was 1720 ppm in strain H-1, 4780 ppm in strain KC and >6680 ppm in strain BJ. In the presence of piperonyl butoxide, an inhibitor of cytochrome P450 monooxygenases, the LC₅₀ for acetamiprid was 312 ppm in strain H-1, 837 ppm in strain KC and 1250 ppm in strain BJ. These results suggested that metabolism by cytochrome P450 monooxygenases is involved in acetamiprid resistance in these strains, though other factors also seem to play a role. Furthermore, cDNA cloning of the nicotinic acetylcholine receptor (nAChR) subunits was performed using degenerate primers, and the presence or absence of a point mutation in nAChR β1 was confirmed. The R81T mutation that had been reported in Myzus persicae (Sulzer) nAChR β1 was not found in F. occidentalis strains tested in this study.     

Oxidative stress potentially enhances FcεRI-mediated leukotriene C4 release dependent on the late-phase increase of intracellular glutathione in mast cells

Cysteinyl leukotrienes (cysLTs), which include leukotriene C₄ (LTC₄), are the predominant class of LTs synthesized by mast cells. CysLTs can induce many of the abnormalities seen in asthma. LTC₄ is generated by the conjugation of LTA₄ with reduced glutathione (GSH) by LTC₄ synthase. During screening of the effects of prostanoids on high-affinity IgE receptor (FcεRI)-mediated LTC₄ release from mast cells, we realized that some prostanoids, including ONO-AE1-259-01 and ONO-AE-248, inhibited LTC₄ release, which was associated with a decrease in the amount of intracellular total GSH. We ascertained that l-buthionine-S,R-sulfoximine (BSO), a selective inhibitor of glutamate-cysteine ligase, inhibited LTC₄ release. In addition, cell-permeable GSH, the glutathione reduced form ethyl ester (GSH-OEt), enhanced LTC₄ release in accordance with the change in intracellular total GSH. Depletion of intracellular total GSH induced by ONO-AE-248 or BSO enhanced FcεRI-mediated LTB₄ release in contrast to LTC₄. Oxidative stress contributes to many pathological conditions including asthma. GSH is a major soluble antioxidant and a cofactor for several detoxifying enzymes including GSH peroxidase. Exposure of mast cells to hydrogen peroxide (H₂O₂) or diamide to mimic oxidative stress unexpectedly increased rather than decreased the intracellular reduced GSH content as well as total GSH in the late phase (i.e., 24 or 48 h after exposure), which was accompanied by an increase in LTC₄ release. In conclusion, FcεRI-mediated LTC₄ release from mast cells is mainly regulated by the amount of intracellular GSH. In some cases, oxidative stress may induce a late-phase increase in intracellular GSH, resulting in enhanced LTC₄ release from mast cells.