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1.
Ecol Evol ; 13(2): e9776, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36789343

ABSTRACT

Birds of prey frequently feature in reintroductions and the hacking technique is typically used. Hacking involves removing large nestlings from donor populations, transferring them to captivity, feeding them ad libitum. Potentially, via the hacking method, the stress of captivity and disruption of parental feeding may be detrimental. Alternatively, the provision of ad libitum food may be advantageous. Although hacking has underpinned reintroduction project successes there has been no research on how the method may affect the health and nutritional status of translocated birds during captivity. We compared blood chemistry data from 55 young White-tailed Eagles, translocated from Norway as part of the species' reintroduction to Scotland, from sampling soon after arriving in captivity and again (≈42 days later) before their release. Numerous significant differences between the first and second samples were found, but no significant interactions showed that the sexes responded similarly to captivity. According to hematological and biochemical metrics, individuals showed several changes during captivity, including in red blood cell parameters, plasma proteins, and white cellular parameters related to the immune system, that indicated improved health status. Captivity with ad libitum food was associated with decreased urea and uric acid values: high values can indicate nutritional stress. Urea values became more normally distributed before release, indicating that ad libitum food had reduced nutritional differences between early nestlings in the season and later ones. Despite plentiful food, both sexes lost body mass before release, suggesting an inherent physiological mechanism to improve flight performance in fledglings. We conclude that hacking improved the health and nutritional status of released eagles which is likely to enable birds to cope with greater costs of exploratory behavior which they may require in reintroduction projects. In this context, we note the absence of survival differences between hacked and wild raptors in previous research.

2.
PLoS One ; 16(8): e0254159, 2021.
Article in English | MEDLINE | ID: mdl-34351932

ABSTRACT

Wind farms can have two broad potential adverse effects on birds via antagonistic processes: displacement from the vicinity of turbines (avoidance), or death through collision with rotating turbine blades. These effects may not be mutually exclusive. Using detailed data from 99 turbines at two wind farms in central Scotland and thousands of GPS-telemetry data from dispersing golden eagles, we tested three hypotheses. Before-and-after-operation analyses supported the hypothesis of avoidance: displacement was reduced at turbine locations in more preferred habitat and with more preferred habitat nearby. After-operation analyses (i.e. from the period when turbines were operational) showed that at higher wind speeds and in highly preferred habitat eagles were less wary of turbines with motionless blades: rejecting our second hypothesis. Our third hypothesis was supported, since at higher wind speeds eagles flew closer to operational turbines; especially-once more-turbines in more preferred habitat. After operation, eagles effectively abandoned inner turbine locations, and flight line records close to rotor blades were rare. While our study indicated that whole-wind farm functional habitat loss through avoidance was the substantial adverse impact, we make recommendations on future wind farm design to minimise collision risk further. These largely entail developers avoiding outer turbine locations which are in and surrounded by swathes of preferred habitat. Our study illustrates the insights which detailed case studies of large raptors at wind farms can bring and emphasises that the balance between avoidance and collision can have several influences.


Subject(s)
Conservation of Natural Resources , Eagles/physiology , Ecosystem , Flight, Animal , Telemetry , Wind , Animal Migration , Animals , Scotland
3.
Glob Chang Biol ; 26(7): 3771-3787, 2020 07.
Article in English | MEDLINE | ID: mdl-32350939

ABSTRACT

Climate change and anthropogenic nitrogen deposition are widely regarded as important drivers of environmental change in alpine habitats. However, due to the difficulties working in high-elevation mountain systems, the impacts of these drivers on alpine breeding species have rarely been investigated. The Eurasian dotterel (Charadrius morinellus) is a migratory wader, which has been the subject of uniquely long-term and spatially widespread monitoring effort in Scotland, where it breeds in alpine areas in dwindling numbers. Here we analyse data sets spanning three decades, to investigate whether key potential drivers of environmental change in Scottish mountains (snow lie, elevated summer temperatures and nitrogen deposition) have contributed to the population decline of dotterel. We also consider the role of rainfall on the species' wintering grounds in North Africa. We found that dotterel declines-in both density and site occupancy of breeding males-primarily occurred on low and intermediate elevation sites. High-elevation sites mostly continued to be occupied, but males occurred at lower densities in years following snow-rich winters, suggesting that high-elevation snow cover displaced dotterel to lower sites. Wintering ground rainfall was positively associated with densities of breeding males two springs later. Dotterel densities were reduced at low and intermediate sites where nitrogen deposition was greatest, but not at high-elevation sites. While climatic factors explained variation in breeding density between years, they did not seem to explain the species' uphill retreat and decline. We cannot rule out the possibility that dotterel have increasingly settled on higher sites previously unavailable due to extensive snow cover, while changes associated with nitrogen deposition may also have rendered lower lying sites less suitable for breeding. Causes of population and range changes in mountain-breeding species are thus liable to be complex, involving multiple anthropogenic drivers of environmental change acting widely across annual and migratory life cycles.


Subject(s)
Birds , Climate Change , Africa, Northern , Animals , Breeding , Male , Population Dynamics , Scotland , Seasons
4.
J Anim Ecol ; 87(6): 1587-1599, 2018 11.
Article in English | MEDLINE | ID: mdl-29975797

ABSTRACT

For many species, there is evidence that breeding performance changes as an individual ages. In iteroparous species, breeding performance often increases through early life and is expected to level out or even decline (senesce) later in life. An individual's sex and conditions experienced in early life may also affect breeding performance and how this changes with age. Long-term monitoring of individuals from reintroduced populations can provide unique opportunities to explore age-related trends in breeding performance that might otherwise be logistically challenging. We used a unique dataset from a reintroduced population of white-tailed eagles Haliaeetus albicilla in Scotland, which has been intensively monitored since their initial reintroduction in 1975, to study age- and sex-specific trends in two measures of breeding performance. This monitoring provided data on the breeding performance of known individuals ranging in age from 3 to 26 years. We also explored changes in breeding performance in relation to early life experience (i.e., whether they were released or fledged in the wild). Breeding performance increased with age in early life in a similar manner for both sexes. We found stronger evidence for senescence in breeding performance in males than females. However, late-life female breeding success was associated with early life experience, while male senescent trends were not apparently impacted by conditions experienced during early life. Sexual differences in senescence mean that older males are less likely to breed successfully compared to older females, and this may influence females' mate changes later in life. This difference may suggest a linked sexual difference in survival rates or the possibility of proactive partner change by females in later life in this typically monogamous biparental species.


Subject(s)
Raptors , Aging , Animals , Breeding , Female , Male , Reproduction , Scotland , Sexual Behavior, Animal
5.
Am J Case Rep ; 18: 1302-1308, 2017 Dec 07.
Article in English | MEDLINE | ID: mdl-29213030

ABSTRACT

BACKGROUND Vertebrobasilar dolichoectasia (VBD) is a complex progressive arterial disease characterized by dilation, elongation, and tortuosity of the vertebral and basilar arteries, and may be congenital or acquired. VBD may lead to progressive compression of the brainstem, cranial nerve abnormalities, and intracranial hemorrhage, but may also be associated with arterial thrombosis, with ischemic stroke as the most common clinical outcome. CASE REPORT Two cases of VBD are presented, both with acute bilateral ophthalmoplegia and cranial nerve palsies, and vertebrobasilar arterial thrombosis that resulted in ischemic stroke. CONCLUSIONS VBD is a complex arterial disease with a variety of clinical manifestation, with bilateral ophthalmoplegia being a rare presentation. Clinical management of VBD is a challenge as there are no current management guidelines. Therefore, clinical management of cases of VBD should be individualized to balance the risks and benefits of treatment options for each patient.


Subject(s)
Brain Infarction/etiology , Intracranial Thrombosis/etiology , Ophthalmoplegia/etiology , Vertebrobasilar Insufficiency/complications , Acute Disease , Aged , Brain Infarction/diagnostic imaging , Cranial Nerve Diseases/etiology , Female , Humans , Intracranial Thrombosis/diagnostic imaging , Male , Middle Aged
6.
PLoS One ; 12(3): e0173956, 2017.
Article in English | MEDLINE | ID: mdl-28306744

ABSTRACT

Understanding the ranging behaviours of species can be helpful in effective conservation planning. However, for many species that are rare, occur at low densities, or occupy challenging environments, this information is often lacking. The Martial Eagle (Polemaetus bellicosus) is a low density apex predator declining in both non-protected and protected areas in southern Africa, and little is known about its ranging behaviour. We use GPS tags fitted to Martial Eagles (n = 8) in Kruger National Park (KNP), South Africa to describe their ranging behaviour and habitat preference. This represents the first time that such movements have been quantified in adult Martial Eagles. Territorial eagles (n = 6) held home ranges averaging ca. 108 km2. Home range estimates were similar to expectations based on inter-nest distances, and these large home range sizes could constrain the carrying capacity of even the largest conservation areas. Two tagged individuals classed as adults on plumage apparently did not hold a territory, and accordingly ranged more widely (ca. 44,000 km2), and beyond KNP boundaries as floaters. Another two territorial individuals abandoned their territories and joined the 'floater' population, and so ranged widely after leaving their territories. These unexpected movements after territory abandonment could indicate underlying environmental degradation. Relatively high mortality of these wide-ranging 'floaters' due to anthropogenic causes (three of four) raises further concerns for the species' persistence. Habitat preference models suggested Martial Eagles used areas preferentially that were closer to rivers, had higher tree cover, and were classed as dense bush rather than open bush or grassland. These results can be used by conservation managers to help guide actions to preserve breeding Martial Eagles at an appropriate spatial scale.


Subject(s)
Conservation of Natural Resources , Eagles/physiology , Ecosystem , Animals , Geographic Information Systems , South Africa
7.
PLoS One ; 12(2): e0172685, 2017.
Article in English | MEDLINE | ID: mdl-28231316

ABSTRACT

Wind farm development can combat climate change but may also threaten bird populations' persistence through collision with wind turbine blades if such development is improperly planned strategically and cumulatively. Such improper planning may often occur. Numerous wind farms are planned in a region hosting the only cinereous vulture population in south-eastern Europe. We combined range use modelling and a Collision Risk Model (CRM) to predict the cumulative collision mortality for cinereous vulture under all operating and proposed wind farms. Four different vulture avoidance rates were considered in the CRM. Cumulative collision mortality was expected to be eight to ten times greater in the future (proposed and operating wind farms) than currently (operating wind farms), equivalent to 44% of the current population (103 individuals) if all proposals are authorized (2744 MW). Even under the most optimistic scenario whereby authorized proposals will not collectively exceed the national target for wind harnessing in the study area (960 MW), cumulative collision mortality would still be high (17% of current population) and likely lead to population extinction. Under any wind farm proposal scenario, over 92% of expected deaths would occur in the core area of the population, further implying inadequate spatial planning and implementation of relevant European legislation with scant regard for governmental obligations to protect key species. On the basis of a sensitivity map we derive a spatially explicit solution that could meet the national target of wind harnessing with a minimum conservation cost of less than 1% population loss providing that the population mortality (5.2%) caused by the operating wind farms in the core area would be totally mitigated. Under other scenarios, the vulture population would probably be at serious risk of extinction. Our 'win-win' approach is appropriate to other potential conflicts where wind farms may cumulatively threaten wildlife populations.


Subject(s)
Conservation of Natural Resources/methods , Energy-Generating Resources , Falconiformes , Models, Theoretical , Wind , Animals , Climate Change , Europe, Eastern
8.
J Anim Ecol ; 85(4): 892-902, 2016 07.
Article in English | MEDLINE | ID: mdl-26990178

ABSTRACT

Deciphering the causes of variation in reproductive success is a fundamental issue in ecology, as the number of offspring produced is an important driver of individual fitness and population dynamics. Little is known, however, about how different factors interact to drive variation in reproduction, such as whether an individual's response to extrinsic conditions (e.g. food availability or predation) varies according to its intrinsic attributes (e.g. age, previous allocation of resources towards reproduction). We used 29 years of reproductive data from marked female tawny owls and natural variation in food availability (field vole) and predator abundance (northern goshawk) to quantify the extent to which extrinsic and intrinsic factors interact to influence owl reproductive traits (breeding propensity, clutch size and nest abandonment). Extrinsic and intrinsic factors appeared to interact to affect breeding propensity (which accounted for 83% of the variation in owl reproductive success). Breeding propensity increased with vole density, although increasing goshawk abundance reduced the strength of this relationship. Owls became slightly more likely to breed as they aged, although this was only apparent for individuals who had fledged chicks the year before. Owls laid larger clutches when food was more abundant. When owls were breeding in territories less exposed to goshawk predation, 99·5% of all breeding attempts reached the fledging stage. In contrast, the probability of breeding attempts reaching the fledging stage in territories more exposed to goshawk predation depended on the amount of resources an owl had already allocated towards reproduction (averaging 87·7% for owls with clutches of 1-2 eggs compared to 97·5% for owls with clutches of 4-6 eggs). Overall, our results suggested that changes in extrinsic conditions (predominantly food availability, but also predator abundance) had the greatest influence on owl reproduction. In response to deteriorating extrinsic conditions (fewer voles and more goshawks), owls appeared to breed more frequently, but allocated fewer resources per breeding attempt. However, intrinsic attributes also appeared to have a relatively small influence on how an individual responded to variation in extrinsic conditions, which indicates that owl reproductive decisions were shaped by a complex series of extrinsic and intrinsic trade-offs.


Subject(s)
Clutch Size/physiology , Predatory Behavior , Reproduction/physiology , Strigiformes/physiology , Age Factors , Animals , Arvicolinae , Ecosystem , Falconiformes , Female , Nesting Behavior , Population Dynamics
9.
J Anim Ecol ; 84(3): 692-701, 2015 May.
Article in English | MEDLINE | ID: mdl-25334013

ABSTRACT

Currently, there is no general agreement about the extent to which predators impact prey population dynamics and it is often poorly predicted by predation rates and species abundances. This could, in part be caused by variation in the type of selective predation occurring. Notably, if predation is selective on categories of individuals that contribute little to future generations, it may moderate the impact of predation on prey population dynamics. However, despite its prevalence, selective predation has seldom been studied in this context. Using recoveries of ringed tawny owls (Strix aluco) predated by 'superpredators', northern goshawks (Accipiter gentilis) as they colonized the area, we investigated the extent to which predation was sex and age-selective. Predation of juvenile owls was disproportionately high. Amongst adults, predation was strongly biased towards females and predation risk appeared to increase with age. This implies age-selective predation may shape the decline in survival with age, observed in tawny owls. To determine whether selective predation can modulate the overall impact of predation, age-based population matrix models were used to simulate the impact of five different patterns of age-selective predation, including the pattern actually observed in the study site. The overall impact on owl population size varied by up to 50%, depending on the pattern of selective predation. The simulation of the observed pattern of predation had a relatively small impact on population size, close to the least harmful scenario, predation on juveniles only. The actual changes in owl population size and structure observed during goshawk colonization were also analysed. Owl population size and immigration were unrelated to goshawk abundance. However, goshawk abundance appeared to interact with owl food availability to have a delayed effect on recruitment into the population. This study provides strong evidence to suggest that predation of other predators is both age and sex-selective and that selective predation of individuals with a low reproductive value may mitigate the overall impact of predators on prey population dynamics. Consequently, our results highlight how accounting for the type of selective predation occurring is likely to improve future predictions of the overall impact of predation.


Subject(s)
Hawks/physiology , Predatory Behavior , Strigiformes/physiology , Age Factors , Animals , England , Female , Food Chain , Male , Models, Biological , Population Dynamics , Sex Factors
10.
BMC Ecol ; 13: 42, 2013 Nov 06.
Article in English | MEDLINE | ID: mdl-24192328

ABSTRACT

BACKGROUND: Dispersal comprises three broad stages - departure from the natal or breeding locations, subsequent travel, and settlement. These stages are difficult to measure, and vary considerably between sexes, age classes, individuals and geographically. We used tracking data from 24 golden eagles, fitted with long-lived GPS satellite transmitters as nestlings, which we followed during their first year. We estimated the timing of emigration from natal sites using ten previously published methods. We propose and evaluate two new methods. The first of these uses published ranging distances of parents as a measure of the natal home range, with the requirement that juveniles must exceed it for a minimum of 10 days (a literature-based measure of the maximum time that a juvenile can survive without food from its parents). The second method uses the biggest difference in the proportion of locations inside and outside of the natal home range smoothed over a 30 day period to assign the point of emigration. We used the latter as the standard against which we compared the ten published methods. RESULTS: The start of golden eagle dispersal occurred from 39 until 250 days after fledging (based on method 12). Previously published methods provided very different estimates of the point of emigration with a general tendency for most to apparently assign it prematurely. By contrast the two methods we proposed provided very similar estimates for the point of emigration that under visual examination appeared to fit the definition of emigration much better. CONCLUSIONS: We have used simple methods to decide when an individual has dispersed - they are rigorous and repeatable. Despite one method requiring much more information, both methods provided robust estimates for when individuals emigrated at the start of natal dispersal. Considerable individual variation in recorded behaviour appears to account for the difficulty capturing the point of emigration and these results demonstrate the potential pitfalls associated with species exhibiting complex dispersal behaviour. We anticipate that coupled with the rapidly increasing availability of tracking data, our new methods will, for at least some species, provide a far simpler and more biologically representative approach to determine the timing of emigration.


Subject(s)
Animal Distribution , Raptors/physiology , Animals , Geographic Information Systems , Scotland
11.
Blood Coagul Fibrinolysis ; 13(3): 187-92, 2002 Apr.
Article in English | MEDLINE | ID: mdl-11943931

ABSTRACT

Thromboembolism is not uncommon in multiple myeloma (MM) patients on treatment, but its pathogenesis remains poorly understood. We report the results of a prospective randomized trial of 62 newly diagnosed MM patients tested at baseline for hypercoagulability and treated with intensive chemotherapy with or without thalidomide in a randomized fashion. During the induction phase, 12 patients (19%) developed evidence of deep venous thrombosis (DVT), which was significantly more common in the thalidomide arm (36%) than in the control group (3%) (P = 0.001). Fourteen patients (23%) were found to have a baseline-reduced response to activated protein C (APC) in the absence of factor V Leiden mutation. Using a Kaplan-Meier analysis, a significantly higher proportion of patients with APC resistance developed DVT (5/14 versus 7/38; P = 0.04) irrespective of thalidomide administration. The risk of DVT was highest (50%) in patients with APC resistance on thalidomide. None of the patients with normal APC response and not receiving thalidomide developed DVT. In conclusion, in this series, acquired APC resistance was present in almost one-quarter of newly diagnosed myeloma patients and significantly increased the risk of DVT.


Subject(s)
Activated Protein C Resistance/etiology , Multiple Myeloma/blood , Thrombophilia/etiology , Venous Thrombosis/epidemiology , Activated Protein C Resistance/epidemiology , Activated Protein C Resistance/genetics , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Blood Coagulation Tests , Cisplatin/administration & dosage , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Dexamethasone/administration & dosage , Doxorubicin/administration & dosage , Etoposide/administration & dosage , Factor V/analysis , Female , Hematopoietic Stem Cell Transplantation , Humans , Incidence , Life Tables , Male , Middle Aged , Multiple Myeloma/complications , Multiple Myeloma/drug therapy , Multiple Myeloma/therapy , Risk , Thalidomide/administration & dosage , Thalidomide/adverse effects , Thalidomide/pharmacology , Vincristine/administration & dosage
12.
Org Lett ; 3(21): 3265-8, 2001 Oct 18.
Article in English | MEDLINE | ID: mdl-11594810

ABSTRACT

[reaction: see text]. A trisaccharide donor containing a cis-Galpalpha(1-->4)Galp linkage was prepared using a synthetic strategy based on chemoenzymatic oligosaccharide synthesis on a soluble polymeric support. Significantly, only retaining glycosyltransferases gave complete reactions, whereas inverting enzymes showed little or no activity with poly(ethylene glycol) (MPEG)-bound lactose as an acceptor. The MPEG-attached trisaccharide was shown to bind to Verotoxin-1 by transfer NOE studies through the Galpalpha(1-->4)Galp portion of the molecule.


Subject(s)
Glycosyltransferases/metabolism , Oligosaccharides/chemical synthesis , Carbohydrate Conformation , Glycosylation , Glycosyltransferases/chemistry , Nuclear Magnetic Resonance, Biomolecular , Oligosaccharides/chemistry , Polyethylene Glycols , Protein Binding , Shiga Toxin 1/metabolism , Trisaccharides/chemical synthesis , Trisaccharides/metabolism
13.
J Am Chem Soc ; 123(23): 5460-4, 2001 Jun 13.
Article in English | MEDLINE | ID: mdl-11389627

ABSTRACT

Static and dynamical Density Functional Theory studies of 2,6-di-O-acetyl-3,4-O-isopropylidene-D-galactopyranosyl cation have shown that this cation can exist in two conformers characterized as (2)S(O) and B(2,5), respectively. The (2)S(O) conformer has the O-2 acyl group equatorial with the carbonyl syn to H-2 and is populated by monocyclic oxocarbenium ions. These conformational features are present in the structurally related glycosyl donor ethyl 2,6-di-O-benzoyl-3,4-O-isopropylidene-beta-D-galactothiopyranoside as determined by X-ray diffraction studies. The B(2,5) conformer has O-2 axial and allows the carbonyl to rotate and close the five-membered ring to form a bicyclic dioxolenium ion. Constraints based on natural internal coordinates were implemented to study this conformational transition. In this way the barrier to interconversion has been determined to be 34 kJ mol(-)(1) with a transition state characterized as (O)S(2) and a pathway involving pseudorotation. Thus, for the first time the structures and energetics of the key ions postulated to be involved in neighboring group assisted glycosylation reactions have been determined.

14.
Int Immunopharmacol ; 1(3): 539-50, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11367537

ABSTRACT

beta-Glucans are polysaccharides that act as nonspecific immune system stimulants. However, many beta-Glucans are sparingly soluble in water. This work describes an oxidative procedure, which solubilizes the beta-Glucan from Saccharomyces cerevisiae and maintains its immunostimulatory properties. Furthermore, the carboxylates at the site of oxidation allow for the conjugation of small molecule immunostimulants. Both the parent oxidized beta-glucan and its conjugates with O-beta-alanyl-5-[6-(N,N'-dimethylamino)purin-9-yl]pentanol stimulate cytotoxic T-lymphocytes (CTLs), B cells and macrophages. In addition, they both stimulate natural killer (NK) cells, a property which the small molecule purine does not possess.


Subject(s)
Adjuvants, Immunologic/chemistry , Adjuvants, Immunologic/pharmacology , Glucans/chemistry , Glucans/pharmacology , Adjuvants, Immunologic/isolation & purification , Animals , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , Carbohydrate Sequence , Female , Glucans/isolation & purification , Humans , In Vitro Techniques , Killer Cells, Natural/drug effects , Killer Cells, Natural/immunology , Macrophages/drug effects , Macrophages/immunology , Mice , Mice, Inbred C57BL , Molecular Sequence Data , Oxidation-Reduction , Saccharomyces cerevisiae/chemistry , T-Lymphocytes, Cytotoxic/drug effects , T-Lymphocytes, Cytotoxic/immunology
15.
Carbohydr Res ; 328(1): 3-16, 2000 Aug 18.
Article in English | MEDLINE | ID: mdl-11005572

ABSTRACT

Neisseria meningitidis trisaccharide [GlcNAc[(1-->3)Galbeta(1-->4)Glc-R], tetrasaccharide [Galbeta(1-->4)GlcNAcbeta(1--> 3)Galbeta(1-->4)Glc-R], and a pentasaccharide [Neu5Acalpha(2-->3)Galbeta(1-->4)GlcNAcbeta(1-->3)G albeta(1-->4)Glc-SPh] were prepared via conventional chemical synthesis, polymer-supported synthesis, and chemoenzymatic methods, starting from D-lactose. The polymer polyethyleneglycol monomethylether (MPEG) and the linker dioxyxylene (DOX) were used with a lactose-bound acceptor to improve the purification process. Several enzymes (LgtA, GalE-LgtB fusion, and CMP-Neu5Ac synthetase/sialyltransferase fusion) were used for syntheses of these oligosaccharides. Excellent stereo- and regioselectivities as well as high yield (> 90% from Gal(1-->4)Glc-SPh) of the pentasaccharide were obtained. Both of the convenient processes are suitable for efficient preparation of target oligosaccharides.


Subject(s)
Antigens, Bacterial/chemistry , Bacterial Proteins , Lipopolysaccharides/chemistry , Neisseria meningitidis/chemistry , Oligosaccharides/chemistry , Polysaccharides, Bacterial/chemistry , Carbohydrate Sequence , Glycosyltransferases/metabolism , Molecular Sequence Data , N-Acetylglucosaminyltransferases/genetics , N-Acetylglucosaminyltransferases/metabolism , Neisseria meningitidis/pathogenicity , Sialyltransferases/genetics , Sialyltransferases/metabolism
16.
Org Lett ; 2(6): 751-3, 2000 Mar 23.
Article in English | MEDLINE | ID: mdl-10754677

ABSTRACT

[formula: see text] Numerous glycoconjugates contain the disaccharide Neu5Ac alpha (2-->3)DGalp. An efficient way to incorporate this disaccharide into synthetic glycoconjugates is to develop a disaccharide building block. This communication reports a chemoenzymatic route to such a building block which requires as few as four steps. Some examples using more chemical steps are also presented, which increase the flexibility. These disaccharide donors were used to prepare synthetic trisaccharides.


Subject(s)
Disaccharides/chemistry , Oligosaccharides/chemistry , Oligosaccharides/chemical synthesis , Sialic Acids , Carbohydrate Conformation , Carbohydrate Sequence , Glycoconjugates/chemistry , Molecular Sequence Data
17.
Carbohydr Res ; 319(1-4): 1-16, 1999 Jun 30.
Article in English | MEDLINE | ID: mdl-10520252

ABSTRACT

As part of our program to design, develop and prepare protective vaccines against the bacterial pathogens Group B Streptococcus, we report the synthesis of a disialylated hexasaccharide. This hexasaccharide represents a portion of the serotype-specific capsular polysaccharide of Type VIII that has the tetrasaccharide repeat unit [beta-L-Rhap-(1-->4)-beta-D-Glcp-(1-->4)-[alpha-Neu5Ac-(2--> 3)]-beta-D- Galp-(1-->4)]n. A tetrasaccharide corresponding to this repeat unit has been synthesized by us [E. Eichler, H.J. Jennings, D.M. Whitfield, J. Carbohydr. Chem., 16 (1997) 385-411]. Since the protective epitopes are believed to involve several repeat units, methods to extend this tetrasaccharide were examined. This objective requires a glycosylation of the unreactive OH-4 of the beta-L-Rhap, which was accomplished by coupling a D-Galp glycosyl trichloroacetimidate donor with a beta-L-Rhap-(1-->4)-D-Glcp acceptor. Subsequent coupling of this trisaccharide as a donor to an alpha-Neu5Ac-(2-->3)-D-Galp disaccharide acceptor gave a pentasaccharide. The pentasaccharide was deprotected and enzymatically sialylated using an alpha-(2-->3)-sialyltransferase from Campylobacter jejuni to give the title hexasaccahride alpha-Neu5Ac-(2-->3)- beta-D-Galp-(1-->4)-beta-L-Rhap-(1-->4)-beta-D-Glcp-(1-->4)-[alpha -Neu5Ac- (2-->3)]-beta-D-Galp-(1-->O)-(CH2)3N3.


Subject(s)
Bacterial Capsules , Oligosaccharides/chemical synthesis , Polysaccharides, Bacterial/chemistry , Sialic Acids/chemical synthesis , Streptococcus agalactiae , Bacterial Vaccines , Carbohydrate Sequence , Molecular Sequence Data
18.
Glycoconj J ; 15(1): 75-8, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9530959

ABSTRACT

It was anticipated that stannylation of carbohydrates could be achieved using tin on a polymer-support. Such immobilization simplifies the purification of the carbohydrate because the toxic tin reagent can be removed by filtration. In this case an alkene linker (3-buten-1-ol) was added to chloromethylated 2% cross-linked polystyrene by etherification. Photochemical hydrostannylation with dibutyltinchlorohydride gave a polymer bound trialkyl tin chloride. The Sn-Cl could be hydrolysed with NaOH to yield a resin with terminal Sn-O bonds. Highly regioselective acylation of methyl alpha-D-mannopyranoside (alphaMeMan) to its 3-O-benzoyl derivative was achieved. Traces of the mono 6-O-benzoate and the 3,6-di-O-benzoate were also obtained. Methyl alpha-D-glucopyranoside was also selectively acylated to its 2-O-benzoate but this reaction gave a more complex mixture. The isolated yields (10-30% based on sugar) were disappointingly low. The yields were improved to about 60% with 5% cross-linked resin.


Subject(s)
Carbohydrates/chemistry , Acylation , Monosaccharides/chemistry , Polymers , Tin/chemistry
19.
Immunol Lett ; 54(1): 59-64, 1996 Dec 01.
Article in English | MEDLINE | ID: mdl-9030983

ABSTRACT

Sclerosing keratitis is the major cause of blindness due to onchocerciasis which results from chronic infection with the filarial parasite Onchocerca volvulus. Using a murine model of onchocercal sclerosing keratitis, we have demonstrated previously that predominantly (> 85%) CD3 + /CD4+ T-cells as well as the IL-2 receptor bearing cells infiltrate into the cornea in vivo during development and progress of the disease. The identification of CD4+ subsets TH1 and TH2 based on the cytokine secretion patterns of murine T-lymphocytes has been useful for understanding the immune basis of resistance and pathogenesis in murine models of several parasitic diseases. The present investigation was carried out to demonstrate whether the local immune response at the corneal lesion due to onchocercal interstitial keratitis correlated with such distinct patterns of cytokine production. For that purpose, mRNA was extracted separately from corneas obtained from the diseased eyes and the normal eyes of A/J mice with onchocercal interstitial keratitis, reverse transcribed and amplified by the polymerase chain reaction with four different cytokine specific primers. In corneas obtained from the eyes affected with onchocercal interstitial keratitis, mRNAs coding for IL-4 and IL-5 were up-regulated compared to the normal eyes having no lesions from the same animals. However, the levels of mRNAs for IL-2 and IFN gamma were found to be the same in the diseased and normal eyes. Taken together, these data suggest that IL-4 and IL-5 producing TH2-lymphocytes are active at the corneal lesion due to onchocercal interstitial keratitis.


Subject(s)
Cornea/immunology , Cytokines/biosynthesis , Onchocerca volvulus/immunology , Onchocerciasis, Ocular/immunology , Animals , Antigens, Helminth/immunology , Cornea/parasitology , Cytokines/genetics , Disease Models, Animal , Interferon-gamma/genetics , Interferon-gamma/immunology , Interleukin-2/biosynthesis , Interleukin-2/genetics , Interleukin-4/biosynthesis , Interleukin-4/genetics , Interleukin-5/biosynthesis , Interleukin-5/genetics , Keratitis/immunology , Mice , Mice, Inbred A , Neovascularization, Pathologic , RNA, Messenger , Th1 Cells/immunology , Th2 Cells/immunology , Up-Regulation
20.
Glycoconj J ; 13(1): 5-17, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8785487

ABSTRACT

A short review of the present status of glycosylation reactions is presented. The reactivity of both proven and newer glycosylation methods are briefly discussed. Emphasis is placed on the control of stereochemistry and regiochemistry. As well, the identification and avoidance of side reactions is covered. Polymer-supported synthesis of oligosaccharides is noted as a promising direction for eliminating some of the problems associated with purification. It is suggested that a better understanding of the mechanism of glycosylation reactions is necessary for future improvements to stereoselectivity and regioselectivity. A key advance would be methods for enhancing the reactivity of weakly nucleophilic hydroxyls.


Subject(s)
Glycoconjugates/chemistry , Glycoconjugates/chemical synthesis , Glycosylation , Carbohydrate Sequence , Hydroxylation , Molecular Sequence Data , Molecular Structure , Stereoisomerism
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