Mammalian Fbh1 is important to restore normal mitotic progression following decatenation stress

We have addressed the role of the F-box helicase 1 (Fbh1) protein during genome maintenance in mammalian cells. For this, we generated two mouse embryonic stem cell lines deficient for Fbh1: one with a homozygous deletion of the N-terminal F-box domain (Fbh1^f/f), and the other with a homozygous disruption (Fbh1^?/?). Consistent with previous reports of Fbh1-deficiency in vertebrate cells, we found that Fbh1^?/? cells show a moderate increase in Rad51 localization to DNA damage, but no clear defect in chromosome break repair. In contrast, we found that Fbh1^f/f cells show a decrease in Rad51 localization to DNA damage and increased cytoplasmic localization of Rad51. However, these Fbh1^f/f cells show no clear defects in chromosome break repair. Since some Rad51 partners and F-box-associated proteins (Skp1-Cul1) have been implicated in progression through mitosis, we considered whether Fbh1 might play a role in this process. To test this hypothesis, we disrupted mitosis using catalytic topoisomerase II inhibitors (bisdioxopiperazines), which inhibit chromosome decatenation. We found that both Fbh1^f/f and Fbh1^?/? cells show hypersensitivity to topoisomerase II catalytic inhibitors, even though the degree of decatenation stress was not affected. Furthermore, following topoisomerase II catalytic inhibition, both Fbh1-deficient cell lines show substantial defects in anaphase separation of chromosomes. These results indicate that Fbh1 is important for restoration of normal mitotic progression following decatenation stress.     

Filter-feeding gelatinous macrozooplankton response to climate change and implications for benthic food supply and global carbon cycle

It is often suggested that gelatinous zooplankton may benefit from anthropogenic pressures of all kinds and in particular from climate change. Large pelagic tunicates, for example, are likely to be favored over other types of macrozooplankton due to their filter-feeding mode, which gives them access to small preys thought to be less affected by climate change than larger preys. In this study, we provide model-based estimate of potential community changes in macrozooplankton composition and estimate for the first time their effects on benthic food supply and on the ocean carbon cycle under two 21st-century climate-change scenarios. Forced with output from an Earth System Model climate projections, our ocean biogeochemical model simulates a large reduction in macrozooplankton biomass in response to anthropogenic climate change, but shows that gelatinous macrozooplankton are less affected than nongelatinous macrozooplankton, with global biomass declines estimated at −2.8% and −3.5%, respectively, for every 1°C of warming. The inclusion of gelatinous macrozooplankon in our ocean biogeochemical model has a limited effect on anthropogenic carbon uptake in the 21st century, but impacts the projected decline in particulate organic matter fluxes in the deep ocean. In subtropical oligotrophic gyres, where gelatinous zooplankton dominate macrozooplankton, the decline in the amount of organic matter reaching the seafloor is reduced by a factor of 2 when gelatinous macrozooplankton are considered (−17.5% vs. −29.7% when gelatinous macrozooplankton are not considered, all for 2100 under RCP8.5). The shift to gelatinous macrozooplankton in the future ocean therefore buffers the decline in deep carbon fluxes and should be taken into account when assessing potential changes in deep carbon storage and the risks that deep ecosystems may face when confronted with a decline in their food source.     

Contrasting Gene Decay in Subterranean Vertebrates: Insights from Cavefishes and Fossorial Mammals

Evolution sometimes proceeds by loss, especially when structures and genes become dispensable after an environmental shift relaxes functional constraints. Subterranean vertebrates are outstanding models to analyze this process, and gene decay can serve as a readout. We sought to understand some general principles on the extent and tempo of the decay of genes involved in vision, circadian clock, and pigmentation in cavefishes. The analysis of the genomes of two Cuban species belonging to the genus Lucifuga provided evidence for the largest loss of eye-specific genes and nonvisual opsin genes reported so far in cavefishes. Comparisons with a recently evolved cave population of Astyanax mexicanus and three species belonging to the Chinese tetraploid genus Sinocyclocheilus revealed the combined effects of the level of eye regression, time, and genome ploidy on eye-specific gene pseudogenization. The limited extent of gene decay in all these cavefishes and the very small number of loss-of-function mutations per pseudogene suggest that their eye degeneration may not be very ancient, ranging from early to late Pleistocene. This is in sharp contrast with the identification of several vision genes carrying many loss-of-function mutations in ancient fossorial mammals, further suggesting that blind fishes cannot thrive more than a few million years in cave ecosystems.     

Studies in the Capparaceae XXX: Capparicordis, a new genus from the neotropics

Capparicordis, genus novum is established for Capparicordis crotonoides, C. tweediana, and C. yunckeri, all new combinations here established for three former species of the New World Capparis, Sect. Colicodendron. The first two are xerophytic shrubs or small trees easily separated by flower color, and the last is a grapple-hook scrambler of which flowers are unknown. They have allopatric distributions: C. crotonoides is found in Peru and Ecuador west of the Andes, C. tweediana from Argentina to Bolivia and Paraguay east of the Andes, whereas C. yunckeri is a rare, local endemic from the arid woodlands near Coyoles in northern Honduras. All have stellate pubescence, broadly cordate to subrotund-reniform leaves with (sub)palmate venation at the leaf blade base; a valvate calyx with closed aestivation; baccate subspherical fruits dehiscent by 2–4 valves (indehiscent in C. yunckeri?); cochleate-reniform seeds surrounded by a pulp-derived sarcotesta densely infiltrated by unbranched, unicellular hairs from the testa; and snow-white embryos. Capparicordis crotonoides has n=8 chromosomes.     

Evolution,diversity and interactions with past human populations of recently extinct Pholidoscelis lizards (Squamata: Teiidae) from the Guadeloupe Islands (French West-Indies)

This paper aims to demonstrate how subfossil bone remains from Pleistocene and Holocene deposits can help to reconstruct the history of recently extinct taxa through the example of Pholidoscelis lizards from the Guadeloupe Islands in the French West Indies. To achieve this, we conducted a new anatomical and zooarchaeological study of fossil Pholidoscelis remains collected from 23 archaeological and paleontological deposits on the Guadeloupe Islands from which this genus is nowadays absent. Our results shed light on the past existence of large Pholidoscelis lizards on all the Guadeloupe islands but also on the difficulties of confident specific identification for these remains. Nevertheless, we suggest a possible past occurrence of the now extinct Pholidoscelis major on nearly all of the Guadeloupe islands. In addition, we identified a new Pholidoscelis species, Pholidoscelis turukaeraensis sp. nov., on Marie-Galante Island, where no Pholidoscelis lizards were previously reported. This new species underwent an increase in size after the end of the Pleistocene period, possibly due to reduced predation pressure. We also highlight the consumption of Pholidoscelis lizards by pre-Columbian Amerindians and the huge impact of European colonization, which led to the extinction of all these lizards in less than 300 years.http://zoobank.org/urn:lsid:zoobank.org:pub:15C39436-A083-483F-B35E-78807B606904     

Improved antibacterial activities of coumarin antibiotics bearing 5',5'-dialkylnoviose: biological activity of RU79115

A new series of coumarin inhibitors of DNA gyrase B bearing a N-propargyloxycarbamate at C-3' of various 5',5'-dialkylnoviose, including RU79115, were synthesised and their antibacterial activities have been delineated. Introduction of dialkyl substituents at 5'5'-position of noviose leads to coumarin analogues with improved in vitro and in vivo antibacterial activity.     

Host-Seeking Behavior and Dispersal of Triatoma infestans,a Vector of Chagas Disease,under Semi-field Conditions

Chagas disease affects millions of people in Latin America. The control of this vector-borne disease focuses on halting transmission by reducing or eliminating insect vector populations. Most transmission of Trypanosoma cruzi, the causative agent of Chagas disease, involves insects living within or very close to households and feeding mostly on domestic animals. As animal hosts can be intermittently present it is important to understand how host availability can modify transmission risk to humans and to characterize the host-seeking dispersal of triatomine vectors on a very fine scale. We used a semi-field system with motion-detection cameras to characterize the dispersal of Triatoma infestans, and compare the behavior of vector populations in the constant presence of hosts (guinea pigs), and after the removal of the hosts. The emigration rate – net insect population decline in original refuge – following host removal was on average 19.7% of insects per 10 days compared to 10.2% in constant host populations (p = 0.029). However, dispersal of T. infestans occurred in both directions, towards and away from the initial location of the hosts. The majority of insects that moved towards the original location of guinea pigs remained there for 4 weeks. Oviposition and mortality were observed and analyzed in the context of insect dispersal, but only mortality was higher in the group where animal hosts were removed (p-value <0.01). We discuss different survival strategies associated with the observed behavior and its implications for vector control. Removing domestic animals in infested areas increases vector dispersal from the first day of host removal. The implications of these patterns of vector dispersal in a field setting are not yet known but could result in movement towards human rooms.     

Transposition of the human Hsmar1 transposon: rate-limiting steps and the importance of the flanking TA dinucleotide in second strand cleavage

Hsmar1 is a member of the mariner family of DNA transposons. Although widespread in nature, their molecular mechanism remains obscure. Many other cut-and-paste elements use a hairpin intermediate to cleave the two strands of DNA at each transposon end. However, this intermediate is absent in mariner, suggesting that these elements use a fundamentally different mechanism for second-strand cleavage. We have taken advantage of the faithful and efficient in vitro reaction provided by Hsmar1 to characterize the products and intermediates of transposition. We report different factors that particularly affect the reaction, which are the reaction pH and the transposase concentration. Kinetic analysis revealed that first-strand nicking and integration are rapid. The rate of the reaction is limited in part by the divalent metal ion-dependent assembly of a complex between transposase and the transposon end(s) prior to the first catalytic step. Second-strand cleavage is the rate-limiting catalytic step of the reaction. We discuss our data in light of a model for the two metal ion catalytic mechanism and propose that mariner excision involves a significant conformational change between first- and second-strand cleavage at each transposon end. Furthermore, this conformational change requires specific contacts between transposase and the flanking TA dinucleotide.     

Epithelial Na+ channel stimulation by n-3 fatty acids requires proximity to a membrane-bound A-kinase-anchoring protein complexed with protein kinase A and phosphodiesterase

Essential polyunsatured fatty acids have been shown to modulate enzymes, channels and transporters, to interact with lipid bilayers and to affect metabolic pathways. We have previously shown that eicosapentanoic acid (EPA, C20:5, n-3) activates epithelial sodium channels (ENaCs) in a cAMP-dependent manner involving stimulation of cAMP-dependent protein kinase (PKA). In the present study, we explored further the mechanism of EPA stimulation of ENaC in A6 cells. Fluorescence resonance energy transfer experiments confirmed activation of PKA by EPA. Consistent with our previous studies, EPA had no further stimulatory effect on amiloride-sensitive transepithelial current (INa) in the presence of CPT-cAMP. Thus, we investigated the effect of EPA on cellular pathways which produce cAMP. EPA did not stimulate adenylate cyclase activity or total cellular cAMP accumulation. However, membrane-bound phosphodiesterase activity was inhibited by EPA from 2.46 pmol/mg of protein/min to 1.3 pmol/mg of protein/min. To investigate the potential role of an A-kinase-anchoring protein (AKAP), we used HT31, an inhibitor of the binding between PKA and AKAPs as well as cerulenin, an inhibitor of myristoylation and palmitoylation. Both agents prevented the stimulatory effect of EPA and CPT-cAMP on INa and drastically decreased the amount of PKA in the apical membrane. Colocalization experiments in A6 cells cotransfected with fluorescently labeled ENaC beta subunit and PKA regulatory subunit confirmed the close proximity of the two proteins and the membrane anchorage of PKA. Last, in A6 cells transfected with a dead mutant of Sgk, an enzyme which up-regulates ENaCs, EPA did not stimulate Na+ current. Our results suggest that stimulation of ENaCs by EPA occurs via SGK in membrane-bound compartments containing an AKAP, activated PKA, and a phosphodiesterase.