A Novel Antigen Sensitive to Calcium Chelation That is Associated with the Tip Links and Kinocilial Links of Sensory Hair Bundles

Tip links are extracellular, cell-surface-associated filaments of unknown molecular composition that are thought to gate the mechanotransducer channel of the sensory hair cell. They disappear from the hair bundle in response to calcium chelation and lanthanum treatment and resist degradation by the protease subtilisin. A monoclonal antibody derived from a hybridoma screen identified a novel antigen associated with tip links, the tip-link antigen. The tip-link antigen is also associated with kinocilial links, subtilisin-resistant filaments that are sensitive to calcium chelation and connect the kinocilium to the tallest stereocilia of the hair bundle. Furthermore, the tip-link antigen is expressed in the retina, where it is associated with the ciliary calyx, a ring of microvilli that surrounds the outer segment of the photoreceptor. The tip-link antigen rapidly disappears from the surface of the hair bundle in response to calcium chelation. It is also subtilisin resistant, relative to the ankle-link antigen, an antigen associated with another type of hair bundle link. The tip-link antigen is lanthanum sensitive and, like tip links, reappears on the surface of the hair bundle after calcium chelation. The monoclonal antibody to the tip-link antigen immunoprecipitates two concanavalin A-reactive polypeptides with apparent molecular masses of 200 and 250 kDa from detergent extracts of the retina. These results provide the first identification of a cell surface antigen associated with tip links, indicate that tip links share properties in common with kinocilial links, and reveal a second epitope that, along with the ankle-link antigen, is common to both sensory hair bundles and the ciliary calyx of photoreceptors

The toxic sheep collar for control of sheep-killing coyotes: A progress report

The toxic sheep collar is the most selective method known for killing coyotes that prey on domestic sheep. The concept dates back to the early 1900's and has been studied at the Denver Wildlife Research Center (DWRC) since 1974. Field tests with sodium cyanide (NaCN) in 1975 were unsuccessful due to repellent properties of the toxicant and to the apparent reluctance of coyotes to attack tethered lambs wearing bulky collars. Coyotes attacked one or more tethered, collared lambs in 7 of the 19 test pastures. In all, 14 collared lambs were attacked. Eight of the collars were punctured but no dead coyotes were recovered. A smaller collar containing diphacinone was field tested in 1976. The diphacinone-filled collars were readily accepted by coyotes and lethal to them, but the slow action (5-16 days between dosing and death) of diphacinone made it difficult to assess the effectiveness of these collars under field conditions. Target flocks containing 1 to 12 collared lambs plus uncollared ewes were placed in 15 fenced pastures from which the larger ranch flocks had been removed after repeated coyote predation. One or more collared lambs were attacked in 11 of the 15 tests. An unknown number of coyotes were killed, and in most tests the subsequent incidence of predation was lower than that before the test. Captive coyotes continued to kill sheep for 4 or 5 days after they received a lethal dose of diphacinone; therefore a faster-acting toxicant is needed. This research has shown that problem coyotes can be killed with toxic collars, but further studies are needed to determine the feasibility of this approach compared with traditional means of control. In most tests to date the frequency of coyote predation has been too low and too irregular to permit effective use of the collar; target flocks were in the field for an average of 10 days before being attacked. The known disadvantages of the method include the need to sacrifice live lambs, the human hazards associated with the use of toxicants under field conditions, and the costs of managing target flocks and other sheep in the problem areas

EFFICACY OF COMPOUND 1080 LIVESTOCK PROTECTION COLLARS FOR KILLING COYOTES THAT ATTACK SHEEP

Efficacy of Compound 1080 LP Collars was studied under pen and field conditions. Coyotes poisoned themselves by attacking collared sheep and biting the collars. In 54 pen tests where 1 or 2 captive coyotes had opportunity to attack 1 collared lamb, 41 lambs were attacked and 26 collars were punctured. Of 25 different coyotes offered lambs with collars containing 5 or 10 mg sodium fluoroacetate (FAC)/ml, 23 coyotes attacked and 21 died after collars were punctured in their first (n = 17), second (n = 3), or fifth (n = 1) test. For 11 captive coyotes that punctured rubber collars, the average time to death was 217 min (range 115 to 436 min). Collars were placed on approximately 3 percent of the sheep on 4 Idaho and 7 Montana sheep ranches. Coyotes attacked 67 uncollared and 68 collared sheep, punctured 32 collars, and may have punctured 2 other collars that were not found. Documented rates of collar puncture were 48% for all attacks on collared sheep and 64% for neck-throat attacks. Eight collars were punctured on fences, thorns or brush. All coyotes that punctured collars probably died, but only 3 dead coyotes were found. Adverse impacts on humans, domestic animals, and nontarget wildlife were not seen. The LP Collar is a safe, effective, and selective technique for removing coyotes that attack sheep

Aminoglycoside-Induced Phosphatidylserine Externalization in Sensory Hair Cells Is Regionally Restricted, Rapid, and Reversible

The aminophospholipid phosphatidylserine (PS) is normally restricted to the inner leaflet of the plasma membrane. During certain cellular processes, including apoptosis, PS translocates to the outer leaflet and can be labeled with externally applied annexin V, a calcium-dependent PS-binding protein. In mouse cochlear cultures, annexin V labeling reveals that the aminoglycoside antibiotic neomycin induces rapid PS externalization, specifically on the apical surface of hair cells. PS externalization is observed within ~75 s of neomycin perfusion, first on the hair bundle and then on membrane blebs forming around the apical surface. Whole-cell capacitance also increases significantly within minutes of neomycin application, indicating that blebbing is accompanied by membrane addition to the hair cell surface. PS externalization and membrane blebbing can, nonetheless, occur independently. Pretreating hair cells with calcium chelators, a procedure that blocks mechanotransduction, or overexpressing a phosphatidylinositol 4,5-biphosphate (PIP2)-binding pleckstrin homology domain, can reduce neomycin-induced PS externalization, suggesting that neomycin enters hair cells via transduction channels, clusters PIP2, and thereby activates lipid scrambling. The effects of short-term neomycin treatment are reversible. After neomycin washout, PS is no longer detected on the apical surface, apical membrane blebs disappear, and surface-bound annexin V is internalized, distributing throughout the supranuclear cytoplasm of the hair cell. Hair cells can therefore repair, and recover from, neomycin-induced surface damage. Hair cells lacking myosin VI, a minus-end directed actin-based motor implicated in endocytosis, can also recover from brief neomycin treatment. Internalized annexin V, however, remains below the apical surface, thereby pinpointing a critical role for myosin VI in the transport of endocytosed material away from the periphery of the hair cell

Malaria intervention scale-up in Africa : effectiveness predictions for health programme planning tools, based on dynamic transmission modelling

Scale-up of malaria prevention and treatment needs to continue to further important gains made in the past decade, but national strategies and budget allocations are not always evidence-based. Statistical models were developed summarizing dynamically simulated relations between increases in coverage and intervention impact, to inform a malaria module in the Spectrum health programme planning tool.; The dynamic Plasmodium falciparum transmission model OpenMalaria was used to simulate health effects of scale-up of insecticide-treated net (ITN) usage, indoor residual spraying (IRS), management of uncomplicated malaria cases (CM) and seasonal malaria chemoprophylaxis (SMC) over a 10-year horizon, over a range of settings with stable endemic malaria. Generalized linear regression models (GLMs) were used to summarize determinants of impact across a range of sub-Sahara African settings.; Selected (best) GLMs explained 94-97 % of variation in simulated post-intervention parasite infection prevalence, 86-97 % of variation in case incidence (three age groups, three 3-year horizons), and 74-95 % of variation in malaria mortality. For any given effective population coverage, CM and ITNs were predicted to avert most prevalent infections, cases and deaths, with lower impacts for IRS, and impacts of SMC limited to young children reached. Proportional impacts were larger at lower endemicity, and (except for SMC) largest in low-endemic settings with little seasonality. Incremental health impacts for a given coverage increase started to diminish noticeably at above ~40 % coverage, while in high-endemic settings, CM and ITNs acted in synergy by lowering endemicity. Vector control and CM, by reducing endemicity and acquired immunity, entail a partial rebound in malaria mortality among people above 5 years of age from around 5-7 years following scale-up. SMC does not reduce endemicity, but slightly shifts malaria to older ages by reducing immunity in child cohorts reached.; Health improvements following malaria intervention scale-up vary with endemicity, seasonality, age and time. Statistical models can emulate epidemiological dynamics and inform strategic planning and target setting for malaria control

Paléophytogéographie et paléoclimats postglaciaires dans l’ouest du Bas-Saint-Laurent, Québec

L'analyse pollinique des sédiments de quatre lacs du Bas-Saint-Laurent et de la Côte-du-Sud permet de retracer l'existence d'une phase initiale de toundra s'étendant sur une durée estimée à 500-1000 ans, après à la déglaciation. Cette toundra montre un développement progressif à partir d'un quasi-désert jusqu'à un stade arbustif à bouleau glanduleux, en passant par un stade herbacé riche en plantes arctiques-alpines dont la présence est confirmée par l'analyse macrofossile. L'accumulation organique dans les lacs ne survient que vers 9500-9200 BP, soit plus de 2000 ans après la déglaciation, et correspond à l'arrivée des premiers arbres, d'après les macrorestes. Le tardiglaciaire régional paraît donc avoir été climatiquement très rigoureux par rapport aux régions sises au sud-ouest et au sud, dans les Appalaches. Les forêts sont restées ouvertes jusque vers 8000 BP, constituées surtout de l'épinette noire, des peupliers, du mélèze et du bouleau blanc. La zone pollinique correspondante est dominée par l'aulne crispé, qui a dû jouer un rôle important dans le couvert végétal durant une période caractérisée par une forte incidence des feux. Par la suite, la végétation moderne s'est établie, soit une mosaïque de sapinières et d'érablières avec sensiblement les mêmes séquences physiographiques et les mêmes gradients phytogéographiques régionaux que ceux actuellement constatés dans ce secteur des Appalaches. Les cédrières tourbeuses et les sapinières humides à thuya répandues actuellement dans les basses terres estuariennes et à la marge nord du plateau appalachien ne se sont toutefois développées que vers 3600 ans avant l'actuel. L'Optimum climatique holocene n'est clairement marqué que par une plus grande abondance du pin blanc de 7000 à 3600 ans BP, notamment à la marge nord du plateau appalachien.Postglacial paleophytogeography and paleoclimates in the western part of the Lower Saint Lawrence River region, Québec. Pollen analysis of the sediments of four lakes in the Lower Saint Lawrence River region, north of Maine, shows that tundra vegetation existed during an estimated period of 500 to 1000 years following ice retreat. Progressive development of the tundra from a quasi-desert to a shrub stage with dwarf birch, through an herb stage rich in arctic-alpine taxa is confirmed by macrofossil analysis. Organic sedimentation in the lakes started only around 9500-9200 BP, that is to say more than 2000 years after ice retreat, and is coincident with the arrival of the first trees (macrofossils) in the area. The regional late-glacial climate was thus apparently very harsh, compared to the Appalachian regions located to the south and southwest. Black spruce, the poplars, larch and white birch comprised the forests which remained open until around 8000 BP. The corresponding pollen zone is dominated by green alder which played a major role in the plant cover during a period characterized by a great incidence of fire. Afterwards, the modern vegetation developed, corresponding to a mosaic of fir and maple communities with physiographic sequences and regional phytogeographic gradients similar to those present today within this section of the Appalachian range. Eastern white cedar, which nowadays occupies the wet or boggy sites of the estuarine lowlands and of the northern margin of the Appalachian plateau, whether in pure stands or with balsam fir, began to increase by 3600 BP. The Holocene Climatic Optimum is clearly marked in the study area only by a greater abundance of white pine, especially at the northern margin of the Appalachian plateau between 7000 abd 3600 BP.Mit der Pollenanalyse der Sedimente von vier Seen IaBt sich der Beginn einer Tundra-Phase nachweisen, die nach der Enteisung schâtzungsweise 500-1000 Jahre dauerte. Diese Tundra zeigt eine progressive Entwicklung, ausgehend von einer Quasi-wiiste bis hin zu einem Buschstadium mit Zwergbirke uber ein Pflanzenstadium, das reich an arktisch-alpinen Pflanzen war, deren Vorkommen durch die makrofossile Analyse bestàtigt wird. Die organische Sedimentierung in den Seen tritt erst gegen 9500-9200 Jahre v.u.Z. auf, d.h. uber 2000 Jahre nach Enteisung, und sie entspricht der Ankunft der ers-ten Baume, den Makroresten nach zu schlieBen. Das régionale Spâtglazial scheint demnach klimatisch sehr rauh gewesen zu sein im Vergleich zu den sudwestlich und sudlich gelegenen Gebieten in den Appa-lachen. Die Wàlder blieben bis gegen 8000 v.u.Z. offen und bestanden vor allem aus Schwarztanne, Pappel, Làrche und WeiB-birke. Das entsprechende Pollengebiet ist dominiert von Grunerle, welche eine wichtige RoIIe in der Pflanzendecke gespielt haben mu(3, in einer Zeit, in der gehâuft Brànde auftraten. In der Folgezeit hat sich die moderne Vegetation angesiedelt, d.h. ein Mosaik von Tannen- und Ahornwàldern. Indessen haben die torfhaltigen Zedernwàlder und die feuch-ten Thuja-Tannenwâlder, die gegenwartig in den Mundungs-Niederungen und am Nord-saum des Appalachenplateaus verbreitet sind, sich erst gegen 3600 v.u.Z. entwickelt. Das KIimatische Optimum im Holozan ist nur durch eine grôBere FuIIe der WeiBtanne von 7000 bis 3600 Jahre v.u.Z. klar gekennzeichnet

COYOTES, SHEEP AND LITHIUM CHLORIDE

The use of LiCl-treated baits and carcasses has been advocated as a means of controlling coyote predation on sheep through a process known as aversive conditioning or taste aversion. While some investigators have made well publicized claims of damage reduction through the use of LiCl on sheep ranges, other researchers have experienced difficulty establishing prey aversion in captive coyotes. The conflicting results suggest a need for extensive, carefully controlled research in both pen and field situations before valid conclusions can be reached regarding aversive conditioning as a depredations control method

COYOTES, SHEEP AND LITHIUM CHLORIDE

The use of LiCl-treated baits and carcasses has been advocated as a means of controlling coyote predation on sheep through a process known as aversive conditioning or taste aversion. While some investigators have made well publicized claims of damage reduction through the use of LiCl on sheep ranges, other researchers have experienced difficulty establishing prey aversion in captive coyotes. The conflicting results suggest a need for extensive, carefully controlled research in both pen and field situations before valid conclusions can be reached regarding aversive conditioning as a depredations control method