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171.
Clare McW. H. Benskin Kenneth Wilson Keith Jones and Ian R. Hartley 《Biological reviews of the Cambridge Philosophical Society》2009,84(3):349-373
The importance of wild birds as potential vectors of disease has received recent renewed empirical interest, especially regarding human health. Understanding the spread of bacterial pathogens in wild birds may serve as a useful model for examining the spread of other disease organisms, both amongst birds, and from birds to other taxa. Information regarding the normal gastrointestinal bacterial flora is limited for the majority of wild bird species, with the few well-studied examples concentrating on bacteria that are zoonotic and/or relate to avian species of commercial interest. However, most studies are limited by small sample sizes, the frequent absence of longitudinal data, and the constraints of using selective techniques to isolate specific pathogens. The pathogenic genera found in the gut are often those suspected to exist in the birds' habitat, and although correlations are made between bacterial pathogens in the avian gut and those found in their foraging grounds, little is known about the effect of the pathogen on the host, unless the causative organism is lethal. In this review, we provide an overview of the main bacterial pathogens isolated from birds (with particular emphasis on enteropathogenic bacteria) which have the potential to cause disease in both birds and humans, whilst drawing attention to the limitations of traditional detection methods and possible study biases. We consider factors likely to affect the susceptibility of birds to bacterial pathogens, including environmental exposure and heterogeneities within the host population, and present probable avenues of disease transmission amongst birds and from birds to other animal taxa. Our primary aim is to identify gaps in current knowledge and to propose areas for future study. 相似文献
172.
Taila Hartley Madura Siva Elida Lai Tracy Teodoro Liling Zhang Allen Volchuk 《BMC cell biology》2010,11(1):59
Background
Cells respond to endoplasmic reticulum stress (ER) stress by activating the unfolded protein response. To study the ER stress response in pancreatic β-cells we developed a model system that allows for pathophysiological ER stress based on the Akita mouse. This mouse strain expresses a mutant insulin 2 gene (C96Y), which prevents normal proinsulin folding causing ER stress and eventual β-cell apoptosis. A double-stable pancreatic β-cell line (pTet-ON INS-1) with inducible expression of insulin 2 (C96Y) fused to EGFP was generated to study the ER stress response. 相似文献173.
Masterson LA Spanswick VJ Hartley JA Begent RH Howard PW Thurston DE 《Bioorganic & medicinal chemistry letters》2006,16(2):252-256
The design, synthesis and evaluation of four novel pyrrolo[2,1-c][1,4]benzodiazepine (PBD) prodrugs (1a,b and 2a,b; ) for potential use in carboxypeptidase G2 (CPG2)-based antibody-directed enzyme prodrug therapy (ADEPT) is reported. Although all four prodrugs were shown to be less cytotoxic than the released parent PBDs 3 and 4, the urea prodrugs 1b and 2b were found to be too unstable for use in ADEPT, whereas carbamates 1a and 2a are both stable in an aqueous environment and are good substrates for CPG2. 相似文献
174.
Optimal allocation of Red List assessments to guide conservation of biodiversity in a rapidly changing world
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Virgilio Hermoso Stephanie Renee Januchowski‐Hartley Simon Linke David Dudgeon Paulo Petry Peter McIntyre 《Global Change Biology》2017,23(9):3525-3532
The IUCN Red List is the most extensive source of conservation status assessments for species worldwide, but important gaps in coverage remain. Here, we demonstrate the use of a spatial prioritization approach to efficiently prioritize species assessments to achieve increased and up‐to‐date coverage efficiently. We focus on freshwater fishes, which constitute a significant portion of vertebrate diversity, although comprehensive assessments are available for only 46% of species. We used marxan to identify ecoregions for future assessments that maximize the coverage of species while accounting for anthropogenic stress. We identified a set of priority regions that would help assess one‐third (ca 4000 species) of all freshwater fishes in need of assessment by 2020. Such assessments could be achieved without increasing current investment levels. Our approach is suitable for any taxon and can help ensure that species threat assessments are sufficiently complete to guide global conservation efforts in a rapidly changing world. 相似文献
175.
Climate change and nesting behaviour in vertebrates: a review of the ecological threats and potential for adaptive responses
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Mark C. Mainwaring Iain Barber Denis C. Deeming David A. Pike Elizabeth A. Roznik Ian R. Hartley 《Biological reviews of the Cambridge Philosophical Society》2017,92(4):1991-2002
Nest building is a taxonomically widespread and diverse trait that allows animals to alter local environments to create optimal conditions for offspring development. However, there is growing evidence that climate change is adversely affecting nest‐building in animals directly, for example via sea‐level rises that flood nests, reduced availability of building materials, and suboptimal sex allocation in species exhibiting temperature‐dependent sex determination. Climate change is also affecting nesting species indirectly, via range shifts into suboptimal nesting areas, reduced quality of nest‐building environments, and changes in interactions with nest predators and parasites. The ability of animals to adapt to sustained and rapid environmental change is crucial for the long‐term persistence of many species. Many animals are known to be capable of adjusting nesting behaviour adaptively across environmental gradients and in line with seasonal changes, and this existing plasticity potentially facilitates adaptation to anthropogenic climate change. However, whilst alterations in nesting phenology, site selection and design may facilitate short‐term adaptations, the ability of nest‐building animals to adapt over longer timescales is likely to be influenced by the heritable basis of such behaviour. We urgently need to understand how the behaviour and ecology of nest‐building in animals is affected by climate change, and particularly how altered patterns of nesting behaviour affect individual fitness and population persistence. We begin our review by summarising how predictable variation in environmental conditions influences nest‐building animals, before highlighting the ecological threats facing nest‐building animals experiencing anthropogenic climate change and examining the potential for changes in nest location and/or design to provide adaptive short‐ and long‐term responses to changing environmental conditions. We end by identifying areas that we believe warrant the most urgent attention for further research. 相似文献
176.
177.
Boyden ED Campos-Xavier AB Kalamajski S Cameron TL Suarez P Tanackovic G Tanackovich G Andria G Ballhausen D Briggs MD Hartley C Cohn DH Davidson HR Hall C Ikegawa S Jouk PS König R Megarbané A Nishimura G Lachman RS Mortier G Rimoin DL Rogers RC Rossi M Sawada H Scott R Unger S Valadares ER Bateman JF Warman ML Superti-Furga A Bonafé L 《American journal of human genetics》2011,(6):767-772
Spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type (lepto-SEMDJL, aka SEMDJL, Hall type), is an autosomal dominant skeletal disorder that, in spite of being relatively common among skeletal dysplasias, has eluded molecular elucidation so far. We used whole-exome sequencing of five unrelated individuals with lepto-SEMDJL to identify mutations in KIF22 as the cause of this skeletal condition. Missense mutations affecting one of two adjacent amino acids in the motor domain of KIF22 were present in 20 familial cases from eight families and in 12 other sporadic cases. The skeletal and connective tissue phenotype produced by these specific mutations point to functions of KIF22 beyond those previously ascribed functions involving chromosome segregation. Although we have found Kif22 to be strongly upregulated at the growth plate, the precise pathogenetic mechanisms remain to be elucidated. 相似文献
178.
Chavda S Liu Y Babu B Davis R Sielaff A Ruprich J Westrate L Tronrud C Ferguson A Franks A Tzou S Adkins C Rice T Mackay H Kluza J Tahir SA Lin S Kiakos K Bruce CD Wilson WD Hartley JA Lee M 《Biochemistry》2011,50(15):3127-3136
With the aim of incorporating a recognition element that acts as a fluorescent probe upon binding to DNA, three novel pyrrole (P) and imidazole (I)-containing polyamides were synthesized. The compounds contain a p-anisylbenzimidazolecarboxamido (Hx) moiety attached to a PP, IP, or PI unit, giving compounds HxPP (2), HxIP (3), and HxPI (4), respectively. These fluorescent hybrids were tested against their complementary nonfluorescent, non-formamido tetraamide counterparts, namely, PPPP (5), PPIP (6), and PPPI (7) (cognate sequences 5'-AAATTT-3', 5'-ATCGAT-3', and 5'-ACATGT-3', respectively). The binding affinities for both series of polyamides for their cognate and noncognate sequences were ascertained by surface plasmon resonance (SPR) studies, which revealed that the Hx-containing polyamides gave binding constants in the 10(6) M(-1) range while little binding was observed for the noncognates. The binding data were further compared to the corresponding and previously reported formamido-triamides f-PPP (8), f-PIP (9), and f-PPI (10). DNase I footprinting studies provided additional evidence that the Hx moiety behaved similarly to two consecutive pyrroles (PP found in 5-7), which also behaved like a formamido-pyrrole (f-P) unit found in distamycin and many formamido-triamides, including 8-10. The biophysical characterization of polyamides 2-7 on their binding to the abovementioned DNA sequences was determined using thermal melts (ΔT(M)), circular dichroism (CD), and isothermal titration calorimetry (ITC) studies. Density functional calculations (B3LYP) provided a theoretical framework that explains the similarity between PP and Hx on the basis of molecular electrostatic surfaces and dipole moments. Furthermore, emission studies on polyamides 2 and 3 showed that upon excitation at 322 nm binding to their respective cognate sequences resulted in an increase in fluorescence at 370 nm. These low molecular weight polyamides show promise for use as probes for monitoring DNA recognition processes in cells. 相似文献
179.
Benzoyl and cinnamoyl nitrogen mustard derivatives of benzoheterocyclic analogues of the tallimustine: synthesis and antitumour activity 总被引:1,自引:0,他引:1
Baraldi PG Romagnoli R Giovanna Pavani M del Carmen Nunez M Bingham JP Hartley JA 《Bioorganic & medicinal chemistry》2002,10(5):1611-1618
A series of benzoyl and cinnamoyl nitrogen mustards tethered to different benzoheterocycles and to oligopyrroles structurally related to netropsin consisting of two pyrrole-amide units and terminating with an amidine moiety have been synthesised and a structure--activity relationship determined. Derivatives 3--10 have been evaluated for their sequence selective alkylating properties and cytotoxicity against human K562 leukaemia cells. They are 2- to 50-fold less cytotoxic than tallimustine, with compound 8 being the most potent member of this series. Among tallimustine isosters, the compounds with an indole 3 or benzothiophene 6 are 4-fold less cytotoxic than tallimustine, while the compounds with an N-methyl indole or benzofuran showed a 7- and 14-fold reduced cytotoxic potency, respectively. Our preliminary results indicate that these derivatives preferentially bind to AT-rich sequence with a sequence selectivity similar to tallimustine. 相似文献
180.
Angela Logan Helena M. Cochemé Pamela Boon Li Pun Nadezda Apostolova Robin A.J. Smith Lesley Larsen David S. Larsen Andrew M. James Ian M. Fearnley Sebastian Rogatti Tracy A. Prime Peter G. Finichiu Anna Dare Edward T. Chouchani Victoria R. Pell Carmen Methner Caroline Quin Stephen J. McQuaker Thomas Krieg Richard C. Hartley Michael P. Murphy 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014