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排序方式: 共有260条查询结果,搜索用时 15 毫秒
201.
Smith TM Olejniczak AJ Zermeno JP Tafforeau P Skinner MM Hoffmann A Radovčić J Toussaint M Kruszynski R Menter C Moggi-Cecchi J Glasmacher UA Kullmer O Schrenk F Stringer C Hublin JJ 《Journal of human evolution》2012,62(3):395-411
Recent humans and their fossil relatives are classified as having thick molar enamel, one of very few dental traits that distinguish hominins from living African apes. However, little is known about enamel thickness in the earliest members of the genus Homo, and recent studies of later Homo report considerable intra- and inter-specific variation. In order to assess taxonomic, geographic, and temporal trends in enamel thickness, we applied micro-computed tomographic imaging to 150 fossil Homo teeth spanning two million years. Early Homo postcanine teeth from Africa and Asia show highly variable average and relative enamel thickness (AET and RET) values. Three molars from South Africa exceed Homo AET and RET ranges, resembling the hyper thick Paranthropus condition. Most later Homo groups (archaic European and north African Homo, and fossil and recent Homo sapiens) possess absolutely and relatively thick enamel across the entire dentition. In contrast, Neanderthals show relatively thin enamel in their incisors, canines, premolars, and molars, although incisor AET values are similar to H. sapiens. Comparisons of recent and fossil H. sapiens reveal that dental size reduction has led to a disproportionate decrease in coronal dentine compared with enamel (although both are reduced), leading to relatively thicker enamel in recent humans. General characterizations of hominins as having ‘thick enamel’ thus oversimplify a surprisingly variable craniodental trait with limited taxonomic utility within a genus. Moreover, estimates of dental attrition rates employed in paleodemographic reconstruction may be biased when this variation is not considered. Additional research is necessary to reconstruct hominin dietary ecology since thick enamel is not a prerequisite for hard-object feeding, and it is present in most later Homo species despite advances in technology and food processing. 相似文献
202.
203.
Souza-Fagundes EM Frank AO Feldkamp MD Dorset DC Chazin WJ Rossanese OW Olejniczak ET Fesik SW 《Analytical biochemistry》2012,421(2):742-749
Replication protein A (RPA) interacts with multiple checkpoint proteins and promotes signaling through the ATR kinase, a key regulator of checkpoint pathways in the mammalian response to DNA damage. In cancer cells, increased DNA repair activity contributes to resistance to chemotherapy. Therefore, small molecules that block binding of checkpoint proteins to RPA may inhibit the DNA damage response and, thus, sensitize cancer cells to DNA-damaging agents. Here we report on the development of a homogeneous, high-throughput fluorescence polarization assay for identifying compounds that block the critical protein-protein interaction site in the basic cleft of the 70N domain of RPA (RPA70N). A fluorescein isothiocyanate (FITC)-labeled peptide derived from the ATR cofactor, ATRIP, was used as a probe in the binding assay. The ability of the assay to accurately detect relevant ligands was confirmed using peptides derived from ATRIP, RAD9, MRE11, and p53. The assay was validated for use in high-throughput screening using the Spectrum collection of 2000 compounds. The FPA assay was performed with a Z' factor of ≥ 0.76 in a 384-well format and identified several compounds capable of inhibiting the RPA70N binding interface. 相似文献
204.
ABSTRACT: Co-evolving positions within protein sequences have been used as spatial constraints to develop a computational approach for modeling membrane protein structures. 相似文献
205.
206.
The bacterial protein Hfq participates in the regulation of translation by small noncoding RNAs (sRNAs). Several mechanisms have been proposed to explain the role of Hfq in the regulation by sRNAs binding to the 5′-untranslated mRNA regions. However, it remains unknown how Hfq affects those sRNAs that target the coding sequence. Here, the contribution of Hfq to the annealing of three sRNAs, RybB, SdsR, and MicC, to the coding sequence of Salmonella ompD mRNA was investigated. Hfq bound to ompD mRNA with tight, subnanomolar affinity. Moreover, Hfq strongly accelerated the rates of annealing of RybB and MicC sRNAs to this mRNA, and it also had a small effect on the annealing of SdsR. The experiments using truncated RNAs revealed that the contributions of Hfq to the annealing of each sRNA were individually adjusted depending on the structures of interacting RNAs. In agreement with that, the mRNA structure probing revealed different structural contexts of each sRNA binding site. Additionally, the annealing of RybB and MicC sRNAs induced specific conformational changes in ompD mRNA consistent with local unfolding of mRNA secondary structure. Finally, the mutation analysis showed that the long AU-rich sequence in the 5′-untranslated mRNA region served as an Hfq binding site essential for the annealing of sRNAs to the coding sequence. Overall, the data showed that the functional specificity of Hfq in the annealing of each sRNA to the ompD mRNA coding sequence was determined by the sequence and structure of the interacting RNAs. 相似文献
207.
Evan Perry Jonathan J. Mills Bin Zhao Feng Wang Qi Sun Plamen P. Christov James C. Tarr Tyson A. Rietz Edward T. Olejniczak Taekyu Lee Stephen Fesik 《Bioorganic & medicinal chemistry letters》2019,29(6):786-790
The PD-1 immune checkpoint pathway is a highly validated target for cancer immunotherapy. Despite the potential advantages of small molecule inhibitors over antibodies, the discovery of small molecule checkpoint inhibitors has lagged behind. To discover small molecule inhibitors of the PD-1 pathway, we have utilized a fragment-based approach. Small molecules were identified that bind to PD-L1 and crystal structures of these compounds bound to PD-L1 were obtained. 相似文献
208.
Robert J. Warren II Matt Candeias Adam Labatore Michael Olejniczak Lin Yang 《Journal of Plant Ecology》2019,12(2):201
Aims
A plethora of theories explain species invasion, yet when tested in isolation, support or falsification becomes contingent on study species, system and approach. Our objective was to examine community-level species invasion as a function of multiple competing hypotheses. 相似文献
209.
Jurriaan J H?lzenspies Willem Stoorvogel Ben Colenbrander Bernard AJ Roelen Dagmar R Gutknecht Theo van Haeften 《BMC developmental biology》2009,9(1):8
Background
Mammalian oocytes acquire competence to be fertilized during meiotic maturation. The protein kinase CDC2 plays a pivotal role in several key maturation events, in part through controlled changes in CDC2 localization. Although CDC2 is involved in initiation of maturation, a detailed analysis of CDC2 localization at the onset of maturation is lacking. In this study, the subcellular distribution of CDC2 and its regulatory proteins cyclin B and SPDY in combination with several organelle markers at the onset of pig oocyte maturation has been investigated. 相似文献210.
Gwendoline Kint Kathleen AJ Sonck Geert Schoofs David De Coster Jos Vanderleyden Sigrid CJ De Keersmaecker 《BMC microbiology》2009,9(1):198