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991.
Aude Nicolas Kevin P. Kenna Alan E. Renton Nicola Ticozzi Faraz Faghri Ruth Chia Janice A. Dominov Brendan J. Kenna Mike A. Nalls Pamela Keagle Alberto M. Rivera Wouter van Rheenen Natalie A. Murphy Joke J.F.A. van Vugt Joshua T. Geiger Rick A. Van der Spek Hannah A. Pliner John E. Landers 《Neuron》2018,97(6):1268-1283.e6
992.
Meryl Wang David Zhu Jianwei Zhu Ruth Nussinov Buyong Ma 《Journal of molecular recognition : JMR》2018,31(5)
Deciphering antibody‐protein antigen recognition is of fundamental and practical significance. We constructed an antibody structural dataset, partitioned it into human and murine subgroups, and compared it with nonantibody protein‐protein complexes. We investigated the physicochemical properties of regions on and away from the antibody‐antigen interfaces, including net charge, overall antibody charge distributions, and their potential role in antigen interaction. We observed that amino acid preference in antibody‐protein antigen recognition is entropy driven, with residues having low side‐chain entropy appearing to compensate for the high backbone entropy in interaction with protein antigens. Antibodies prefer charged and polar antigen residues and bridging water molecules. They also prefer positive net charge, presumably to promote interaction with negatively charged protein antigens, which are common in proteomes. Antibody‐antigen interfaces have large percentages of Tyr, Ser, and Asp, but little Lys. Electrostatic and hydrophobic interactions in the Ag binding sites might be coupled with Fab domains through organized charge and residue distributions away from the binding interfaces. Here we describe some features of antibody‐antigen interfaces and of Fab domains as compared with nonantibody protein‐protein interactions. The distributions of interface residues in human and murine antibodies do not differ significantly. Overall, our results provide not only a local but also a global anatomy of antibody structures. 相似文献
993.
994.
Daniel Padfield Angus Buckling Ruth Warfield Chris Lowe Gabriel Yvon‐Durocher 《Ecology letters》2018,21(8):1152-1161
Quantifying variation in ecosystem metabolism is critical to predicting the impacts of environmental change on the carbon cycle. We used a metabolic scaling framework to investigate how body size and temperature influence phytoplankton community metabolism. We tested this framework using phytoplankton sampled from an outdoor mesocosm experiment, where communities had been either experimentally warmed (+ 4 °C) for 10 years or left at ambient temperature. Warmed and ambient phytoplankton communities differed substantially in their taxonomic composition and size structure. Despite this, the response of primary production and community respiration to long‐ and short‐term warming could be estimated using a model that accounted for the size‐ and temperature dependence of individual metabolism, and the community abundance‐body size distribution. This work demonstrates that the key metabolic fluxes that determine the carbon balance of planktonic ecosystems can be approximated using metabolic scaling theory, with knowledge of the individual size distribution and environmental temperature. 相似文献
995.
Ankit X. Sharma Ezekiel B. Quittner-Strom Young Lee Joshua A. Johnson Sarah A. Martin Xinxin Yu Jianping Li John Lu Zheqing Cai Shiuhwei Chen May-yun Wang Yiyi Zhang Mackenzie J. Pearson Andie C. Dorn Jeffrey G. McDonald Ruth Gordillo Hai Yan Dung Thai William L. Holland 《Cell reports》2018,22(7):1760-1773
996.
Maryam Ahmadian Sihao Liu Shannon M. Reilly Nasun Hah Weiwei Fan Eiji Yoshihara Pooja Jha C. Daniel De Magalhaes Filho Sandra Jacinto Andrew V. Gomez Yang Dai Ruth T. Yu Christopher Liddle Annette R. Atkins Johan Auwerx Alan R. Saltiel Michael Downes Ronald M. Evans 《Cell reports》2018,22(11):2849-2859
997.
Denise Karaoglu Hanzatian Annette Schwartz Farid Gizatullin Jamie Erickson Kangwen Deng Ruth Villanueva 《MABS-AUSTIN》2018,10(5):765-777
Therapeutic monoclonal antibodies and endogenous IgG antibodies show limited uptake into the central nervous system (CNS) due to the blood-brain barrier (BBB), which regulates and controls the selective and specific transport of both exogenous and endogenous materials to the brain. The use of natural transport mechanisms, such as receptor-mediated transcytosis (RMT), to deliver antibody therapeutics into the brain have been studied in rodents and monkeys. Recent successful examples include monovalent bispecific antibodies and mono- or bivalent fusion proteins; however, these formats do not have the capability to bind to both the CNS target and the BBB transport receptor in a bivalent fashion as a canonical antibody would. Dual-variable-domain immunoglobulin (DVD-Ig) proteins offer a bispecific format where monoclonal antibody-like bivalency to both the BBB receptor and the therapeutic target is preserved, enabling independent engineering of binding affinity, potency, valency, epitope and conformation, essential for successful generation of clinical candidates for CNS applications with desired drug-like properties. Each of these parameters can affect the binding and transcytosis ability mediated by different receptors on the brain endothelium differentially, allowing exploration of diverse properties. Here, we describe generation and characterization of several different DVD-Ig proteins, specific for four different CNS targets, capable of crossing the BBB through transcytosis mediated by the transferrin receptor 1 (TfR1). After systemic administration of each DVD-Ig, we used two independent methods in parallel to observe specific uptake into the brain. An electrochemiluminescent-based sensitive quantitative assay and a semi-quantitative immunohistochemistry technique were used for brain concentration determination and biodistribution/localization in brain, respectively. Significantly enhanced brain uptake and retention was observed for all TfR1 DVD-Ig proteins regardless of the CNS target or the systemic administration route selected. 相似文献
998.
AbstractSmall game seems to have increased during the Upper Palaeolithic to the detriment of large game on the Iberian Peninsula. The economical and socio-cultural factors associated with this ecological shift represent a widely discussed topic. The present work attempts to elucidate the subsistence strategies occurring through the Late Pleistocene in Iberia using the example of the Molí del Salt (Tarragona, Spain), an archaeological site located in the NE of the Iberian Peninsula. The taphonomical analysis of faunal remains shows a high incidence of human activity on different taxonomical groups, although the European rabbit (Oryctolagus cuniculus) stands out. This taxon presents cut-marks related to various processing activities (e.g. skinning and defleshing) and intentional bone breakage to access marrow. The abundance of specimens with human-induced damage enables us to make inferences regarding the procurement strategies and the occupational patterns at the site, where long and stable occupations seem to have occurred. 相似文献
999.
A novel double nucleotide substitution in the HMG box of the SRY gene associated with Swyer syndrome 总被引:2,自引:0,他引:2
E. Battiloro Barbara Angeletti Maria Cristina Tozzi Lida Bruni Sergio Tondini Piero Vignetti Roberto Verna E. D’Ambrosio 《Human genetics》1997,100(5-6):585-587
We describe a novel double nucleotide substitution in the SRY gene of a 46,XY female with gonadal dysgenesis or Swyer syndrome.
The SRY sequence was analysed by both the single-strand conformational polymorphism assay and direct DNA sequencing of products
from the polymerase chain reaction. A double nucleotide substitution was identified at codon 18 of the conserved HMG box motif,
causing an arginine to asparagine amino-acid substitution. The altered residue is situated in the high mobility group (HMG)-related
box of the SRY protein, a potential DNA-binding domain. Since the mutation abolishes one HhaI recognition site, the results were confirmed by HhaI restriction mapping. No other mutations were found in the remaining regions of the gene. The corresponding DNA region from
the patient’s brother was analysed and found to be normal. We conclude that the SRY mutation in the reported XY female occurred
de novo and is associated with sex reversal.
Received: 16 December 1996 / Accepted: 5 May 1997 相似文献
1000.
Andreas Houben Carolyn R. Leach Dawn Verlin Ruth Rofe Jeremy N. Timmis 《Chromosoma》1997,106(8):513-519
Dot-like micro B chromosomes of Brachycome dichromosomatica were analysed for their sequence composition. Southern hybridization patterns of a total micro B probe to genomic DNA from
plants with and without micro Bs demonstrated that the micro Bs shared sequences with the A chromosomes. In addition to telomere,
rDNA and common A and B chromosome sequences, a new B-specific, highly methylated tandem repeat (Bdm29) was detected. After
in situ hybridization with Bdm29 the entire micro B chromosome was labelled and clustering of the condensed micro Bs could
be observed at interphase. A high number of Bdm29-like sequences were also found in the larger B chromosomes of B. dichromosomatica and in other Bs within the genus Brachycome.
Received: 30 May 1997; in revised form: 20 August 1997 / Accepted: 20 August 1997 相似文献