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Steve Horvath Abu NM Nazmul-Hossain Rodney PE Pollard Frans GM Kroese Arjan Vissink Cees GM Kallenberg Fred KL Spijkervet Hendrika Bootsma Sara A Michie Sven U Gorr Ammon B Peck Chaochao Cai Hui Zhou David TW Wong 《Arthritis research & therapy》2012,14(6):1-13
Bone tissue has an exceptional quality to regenerate to native tissue in response to injury. However, the fracture repair process requires mechanical stability or a viable biological microenvironment or both to ensure successful healing to native tissue. An improved understanding of the molecular and cellular events that occur during bone repair and remodeling has led to the development of biologic agents that can augment the biological microenvironment and enhance bone repair. Orthobiologics, including stem cells, osteoinductive growth factors, osteoconductive matrices, and anabolic agents, are available clinically for accelerating fracture repair and treatment of compromised bone repair situations like delayed unions and nonunions. Preclinical and clinical studies using biologic agents like recombinant bone morphogenetic proteins have demonstrated an efficacy similar or better than that of autologous bone graft in acute fracture healing. A lack of standardized outcome measures for comparison of biologic agents in clinical fracture repair trials, frequent off-label use, and a limited understanding of the biological activity of these agents at the bone repair site have limited their efficacy in clinical applications. 相似文献
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Deregulation of the cell cycle is a hallmark of cancer that enables limitless cell division. To support this malignant phenotype, cells acquire molecular alterations that abrogate or bypass control mechanisms in signaling pathways and cellular checkpoints that normally function to prevent genomic instability and uncontrolled cell proliferation. Consequently, therapeutic targeting of the cell cycle has long been viewed as a promising anti-cancer strategy. Until recently, attempts to target the cell cycle for cancer therapy using selective inhibitors have proven unsuccessful due to intolerable toxicities and a lack of target specificity. However, improvements in our understanding of malignant cell-specific vulnerabilities has revealed a therapeutic window for preferential targeting of the cell cycle in cancer cells, and has led to the development of agents now in the clinic. In this review, we discuss the latest generation of cell cycle targeting anti-cancer agents for breast cancer, including approved CDK4/6 inhibitors, and investigational TTK and PLK4 inhibitors that are currently in clinical trials. In recognition of the emerging population of ER+ breast cancers with acquired resistance to CDK4/6 inhibitors we suggest new therapeutic avenues to treat these patients. We also offer our perspective on the direction of future research to address the problem of drug resistance, and discuss the mechanistic insights required for the successful implementation of these strategies. 相似文献
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Analysis of Feces Samples Collected from a Wild-Bird Garden Feeding Station in Scotland for the Presence of Verocytotoxin-Producing Escherichia coli O157
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Geoffrey Foster Judith Evans Hazel I. Knight Alastair W. Smith George J. Gunn Lesley J. Allison Barti A. Synge Tom W. Pennycott 《Applied microbiology》2006,72(3):2265-2267
Composite wild bird feces collected at regular intervals from a garden feeding station in southwest Scotland over a 3-year period were examined for verocytotoxin-producing Escherichia coli O157. One sample was positive for Escherichia coli O157. The isolate belonged to phage type 21/28 and possessed vtx2, eaeA, and enterohemorrhagic E. coli hlyA genes. 相似文献
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Lawson B Robinson RA Neimanis A Handeland K Isomursu M Agren EO Hamnes IS Tyler KM Chantrey J Hughes LA Pennycott TW Simpson VR John SK Peck KM Toms MP Bennett M Kirkwood JK Cunningham AA 《EcoHealth》2011,8(2):143-153
Finch trichomonosis emerged in Great Britain in 2005 and led to epidemic mortality and a significant population decline of greenfinches, Carduelis chloris and chaffinches, Fringilla coelebs, in the central and western counties of England and Wales in the autumn of 2006. In this article, we show continued epidemic spread of the disease with a pronounced shift in geographical distribution towards eastern England in 2007. This was followed by international spread to southern Fennoscandia where cases were confirmed at multiple sites in the summer of 2008. Sequence data of the ITS1/5.8S/ITS2 ribosomal region and part of the small subunit (SSU) rRNA gene showed no variation between the British and Fennoscandian parasite strains of Trichomonas gallinae. Epidemiological and historical ring return data support bird migration as a plausible mechanism for the observed pattern of disease spread, and suggest the chaffinch as the most likely primary vector. This finding is novel since, although intuitive, confirmed disease spread by migratory birds is very rare and, when it has been recognised, this has generally been for diseases caused by viral pathogens. We believe this to be the first documented case of the spread of a protozoal emerging infectious disease by migrating birds. 相似文献
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本文综述了香菇(Lentinula edodes)的分类历史,确认其在蘑菇目(Agaricales)Tricholomataceae科下的分类地位,并证实了它与多孔菌目(Poriales)Lentinaceae科的Lentinus属没有联系。根据《真菌、地衣汉语学名命名法规》,作者讨论了译为“香菇属”的Lentinus和“小香菇属”的Lentinellus两属的汉语学名问题,提出Lentinus的汉语学名应订正为“韧伞属”,Lentinellus为“螺壳菌属”。香菇所在的Lentinula属的汉语学名建议为“木菇属”。 相似文献
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Multiple forms of tubulin in the cytoskeletal and flagellar microtubules of polytomella 总被引:14,自引:9,他引:5
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The alga polytomella contains several organelles composed of microtubules, including four flagella and hundreds of cytoskeletal microtubules. Brown and co-workers have shown (1976. J. Cell Biol. 69:6-125; 1978, Exp. Cell Res. 117: 313-324) that the flagella could be removed and the cytoskeletans dissociated, and that both structures could partially regenerate in the absence of protein synthesis. Because of this, and because both the flagella and the cytoskeletons can be isolated intact, this organism is particularly suitable for studying tubulin heterogeneity and the incorporation of specific tubulins into different microtubule-containing organelles in the same cell. In order to define the different species of tubulin in polytonella cytoplasm, a (35)S- labeled cytoplasmic fraction was subjected to two cycles of assembly and disassembly in the presence of unlabeled brain tubulin. Comparison of the labeled polytomella cytoplasmic tubulin obtained by this procedure with the tubulin of isolated polytomella flagella by two-dimensional gel electrophoresis showed that, whereas the β-tubulin from both cytoplasmic and flagellar tubulin samples comigrated, the two α-tubulins had distinctly different isoelectic points. As a second method of isolating tubulin from the cytoplasm, cells were gently lysed with detergent and intact cytoskeletons obtained. When these cytoskeletons were exposed to cold temperature, the proteins that were released were found to be highly enriched in tubulin; this tubulin, by itself, could be assembled into microtubules in vitro. The predominant α-tubulin of this in vitro- assembled cytoskeletal tubulin corresponded to the major cytoplasmic α-tubulin obtained by coassembly of labeled polytomella cytoplasmic extract with brain tubulin and was quite distinct from the α-tubulin of purified flagella. These results clearly show that two different microtubule-containing organelles from the same cell are composed of distinct tubulins. 相似文献
8.
A genomic library of partially EcoRI-digested DNA from the lesser snow
goose, Anser caerulescens caerulescens, was constructed in the phage vector
Charon 4. Phage containing only unique sequences were identified by
screening plaques with 32P-labeled genomic DNA. Restriction-fragment-
length polymorphisms (RFLPs) were identified by probing DNA from 11-13 male
birds from the breeding colony at La Perouse Bay. Of the 17 probes
examined, all detected RFLPs with at least one of EcoRi, HindIII, Msp1, and
Taq1. Several of them identified highly variable regions with multiple
alleles. These RFLPs are valuable DNA markers that can be used for (1) the
examination of DNA variation, relatedness, and genetic distance and (2)
assessing paternity and maternity. These data suggest that there are higher
levels of variation of DNA sequence in birds than had previously been
thought to exist.
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Maize endosperm ADP-glucose pyrophosphorylase SHRUNKEN2 and BRITTLE2 subunit interactions 总被引:4,自引:0,他引:4
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ADP-glucose pyrophosphorylase (AGP) represents a key regulatory step in polysaccharide synthesis in organisms ranging from bacteria to plants. Higher plant AGPs are complex in nature and are heterotetramers consisting of two similar but distinct subunits. How the subunits are assembled into enzymatically active polymers is not yet understood. Here, we address this issue by using naturally occurring null mutants of the Shrunken2 (Sh2) and Brittle2 (Bt2) loci of maize as well as the yeast two-hybrid expression system. In the absence of the maize endosperm large AGP subunit (SH2), the BT2 subunit remains as a monomer in the developing endosperm. In contrast, the SH2 protein, in the absence of BT2, is found in a complex of 100 kD. A direct interaction between SH2 and BT2 was proven when they were both expressed in yeast. Several motifs are essential for SH2:BT2 interaction because truncations removing the N or C terminus of either subunit eliminate SH2:BT2 interactions. Analysis of subunit interaction mutants (sim) also identified motifs essential for protein interactions. 相似文献
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Functional electrical stimulation can be used to enable spinal cord injured children to participate in cycling training as part of a fitness programme or exercise testing procedure. Exercise can reduce the impact of secondary health conditions due to the injury. Functional electrical stimulation has shown promising results in adults with a spinal cord injury, but additional considerations are needed to realise the method for the child with spinal cord injury, partly owing to their limited force producing capacity. An electric motor provides a practical means of performing cycling at controlled cadences, exercising for longer durations and can also be used for recreational outdoor cycling. Here, a novel real-time control technique is developed for cadence regulation during cycling. A feedback control structure is developed based on an empirical model derived from separate identification tests and pole placement and then verified in a series of reference-tracking tests. The system produced cadence responses in close agreement with reference values in all cases and demonstrated satisfactory robustness of stability characteristics. This approach moves towards the practical application of the technology as a training tool for paediatric spinal cord injured subjects. 相似文献