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1.
The alpha-like globin gene cluster in rabbits contains embryonic zeta-
globin genes, an adult alpha-globin gene, and theta-globin genes of
undetermined function. The basic arrangement of genes, deduced from
analysis of cloned DNA fragments, is 5'-zeta 0-zeta 1-alpha 1-theta 1- zeta
2-zeta 3-theta 2-3'. However, the pattern of restriction fragments
containing zeta- and theta-globin genes varies among individual rabbits.
Analysis of BamHI fragments of genomic DNA from 24 New Zealand white
rabbits revealed eight different patterns of fragments containing
zeta-globin genes. The large BamHI fragments containing genes zeta 0 and
zeta 1 are polymorphic in length, whereas a 1.9-kb fragment containing the
zeta 2 gene and the 3.5-kb fragment containing the zeta 3 gene do not vary
in size. In contrast to this constancy in the size of the restriction
fragments, the copy number of the zeta 2 and zeta 3 genes does vary among
different rabbits. No length polymorphism was detected in the BamHI
fragments containing the theta-globin genes, but again the copy number
varies for restriction fragments containing the theta 2 gene. The alpha 1-
and theta 1-globin genes are located in a nonpolymorphic 7.2-kb BamHI
fragment. The combined data from hybridization with both zeta and theta
probes shows that the BamHI cleavage pattern does not vary within the
region 5'-alpha 1-theta 1- zeta 2-zeta 3-theta 2-3', but the pattern
genomic blot-hybridization patterns for the progeny of parental rabbits
with different zeta-globin gene patterns shows that the polymorphic
patterns are inherited in a Mendelian fashion. Two different haplotypes
have been mapped based on the genomic blot-hybridization data. The
variation in the alpha-like globin gene cluster in the rabbit population
results both from differences in the copy number of the duplication block
containing the zeta-zeta-theta gene set and from the presence or absence of
polymorphic BamHI sites.
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2.
Trimethyloxonium modification of single batrachotoxin-activated sodium channels in planar bilayers. Changes in unit conductance and in block by saxitoxin and calcium 总被引:13,自引:9,他引:4 下载免费PDF全文
Single batrachotoxin-activated sodium channels from rat brain were modified by trimethyloxonium (TMO) after incorporation in planar lipid bilayers. TMO modification eliminated saxitoxin (STX) sensitivity, reduced the single channel conductance by 37%, and reduced calcium block of inward sodium currents. These effects always occurred concomitantly, in an all-or-none fashion. Calcium and STX protected sodium channels from TMO modification with potencies similar to their affinities for block. Calcium inhibited STX binding to rat brain membrane vesicles and relieved toxin block of channels in bilayers, apparently by competing with STX for the toxin binding site. These results suggest that toxins, permeant cations, and blocking cations can interact with a common site on the sodium channel near the extracellular surface. It is likely that permeant cations transiently bind to this superficial site, as the first of several steps in passing inward through the channel. 相似文献
3.
The effect of several biotic and abiotic factors on the fecundityand hatching success of Calanus helgolandicus was tested duringshort- and long-term incubations. The results show that thevariations of the reproductive responses of C.helgolandicusare time dependent and rely on the type of factor tested. Whenstandardized over a 24 h incubation period, estimates ofin situproduction and egg viability can be obtained with good accuracy. 相似文献
4.
P. Ward A. Atkinson A. W. A. Murray A. G. Wood R. Williams S. A. Poulet 《Polar Biology》1995,15(3):195-208
Zooplankton abundance and biomass were determined during January 1990 at two stations to the north-west of South Georgia using a Longhurst Hardy Plankton Recorder (LHPR). At both shelf and oceanic station sites, zooplankton biomass, (excluding Euphausia superba), was found to be ca. 13 g dry mass m–2. Copepods and small euphausiids dominated the catches. These estimates are over 4 times higher than values generally reported for the Southern Ocean and may reflect firstly, the high productivity of the study area, secondly, the time of year, summer, when biomass for many species is maximal, and thirdly, the high sampling efficiency of the LHPR. Principal components analysis disclosed similarities and differences between adjacent depth strata in terms of abundance, biomass and species composition. At both stations most variability occurred in the mixed layer (0–60 m) and thermocline (60–120 m) with depth horizons below this being more homogeneous. Diel migrations were observed for most taxa with abundance increasing in the mixed layer at night. At the oceanic station, species and higher taxa belonging to the mesopelagic community were generally well spread throughout this domain and, with the exception of Pleuromamma robusta and Metridia curticauda, showed little evidence of migration. The grazing impact of the epipelagic community (copepods and small euphausiids) was estimated to remove 3–4% of the microbial standing stock day–1 and a conservative 25% and 56% of daily primary production at the oceanic and shelf stations respectively. 相似文献
5.
Christina Gros Laura Chauvigné Ana?s Poulet Yoann Menon Frédéric Ausseil Isabelle Dufau Paola B. Arimondo 《Nucleic acids research》2013,41(19):e185
DNA methylation is an important epigenetic mark in eukaryotes, and aberrant pattern of this modification is involved in numerous diseases such as cancers. Interestingly, DNA methylation is reversible and thus is considered a promising therapeutic target. Therefore, there is a need for identifying new small inhibitors of C5 DNA methyltransferases (DNMTs). Despite the development of numerous in vitro DNMT assays, there is a lack of reliable tests suitable for high-throughput screening, which can also give insights into inhibitor mechanisms of action. We developed a new test based on scintillation proximity assay meeting these requirements. After optimizing our assay on human DNMT1 and calibrating it with two known inhibitors, we carried out S-Adenosyl-l-Methionine and DNA competition studies on three inhibitors and were able to determine each mechanism of action. Finally, we showed that our test was applicable to 3 other methyltransferases sources: human DNMT3A, bacterial M.SssI and cellular extracts as well. 相似文献
6.
Abstract Opportunistic sightings and strandings of Caperea marginata (n=196) from the vicinity of Australia and New Zealand (1884 to early 2007) were used to relate geographic and temporal patterns to oceanographic and broad-scale climatic variability. Records were not uniformly distributed along the coast and more (69%) were from Australia than New Zealand. Seven coastal whale ‘hotspots’ were identified which accounted for 61% of records with locality data. Half of the hotspot records were from southeast (37) and northwest (20) Tasmania—others each had 9–15 events. Upwelling and/or high zooplankton abundance has been documented near all whale hotspots. Records of C. marginata occurred in all months, with 75% in spring and summer. Inter-annual variability showed broad agreement between increased whale records (usually in spring/summer) and strongly positive ‘Niño 3.4’ during 1980–1995 but not thereafter. Coastal upwelling and productivity increase during climatic phenomena such as El Niño and are likely to be quickly beneficial to plankton-feeding whales such as C. marginata. 相似文献
7.
An Evaluation of the Impact of PD‐1 Pathway Blockade on Reproductive Safety of Therapeutic PD‐1 Inhibitors 下载免费PDF全文
Frederique M. Poulet Jayanthi J. Wolf Danuta J. Herzyk Joseph J. DeGeorge 《Birth defects research. Part B, Developmental and reproductive toxicology》2016,107(2):108-119
This report discusses the principles of reproductive toxicity risk assessment for biopharmaceuticals blocking the PD‐1/programmed cell death ligand 1 (PD‐L1) pathway, which have been developed for the treatment of patients with advanced malignancies. The PD‐1/PD‐L1 pathway is a T‐cell co‐inhibitory pathway that normally maintains immune tolerance to self. Its role in pregnancy is to maintain immune tolerance to the fetal allograft. In cancer patients, this signaling pathway is hijacked by some neoplasms to avoid immune destruction. PD‐1/PD‐L1‐blocking agents enhance functional activity of the target lymphocytes to eventually cause immune rejection of the tumor. A therapeutic blockade of PD‐1/PD‐L1 pathway that occurs at full target engagement provides a unique challenge to address the risk to pregnancy because disruption of the same pathway may also reduce or abrogate maternal immune tolerance to the fetal alloantigens inherited through the father. Typically, nonclinical reproductive and developmental toxicity (DART) studies in animals (rats and rabbits) with clinical drug candidates are conducted to identify potential risk in humans and to determine exposure margin for the effects on reproduction as part of the risk assessment. However, for biopharmaceuticals for which the desired mechanism of action cannot be separated from potential deleterious effects to the fetus and when the only relevant toxicology species is nonhuman primate (NHP), the risk to reproduction can be predicted by a mechanism‐based assessment using data generated from murine surrogate models as supportive information without conducting DART in NHPs. Such an approach has been used in the evaluation of pregnancy risk of anti‐PD‐1 agent, pembrolizumab, and has been demonstrated as an important alternative to performing DART studies in NHPs 相似文献
8.
Vilizzi Lorenzo Copp Gordon H. Adamovich Boris Almeida David Chan Joleen Davison Phil I. Dembski Samuel Ekmekçi F. Güler Ferincz Árpád Forneck Sandra C. Hill Jeffrey E. Kim Jeong-Eun Koutsikos Nicholas Leuven Rob S. E. W. Luna Sergio A. Magalhães Filomena Marr Sean M. Mendoza Roberto Mourão Carlos F. Neal J. Wesley Onikura Norio Perdikaris Costas Piria Marina Poulet Nicolas Puntila Riikka Range Inês L. Simonović Predrag Ribeiro Filipe Tarkan Ali Serhan Troca Débora F. A. Vardakas Leonidas Verreycken Hugo Vintsek Lizaveta Weyl Olaf L. F. Yeo Darren C. J. Zeng Yiwen 《Reviews in Fish Biology and Fisheries》2019,29(3):529-568
Reviews in Fish Biology and Fisheries - The freshwater Fish Invasiveness Screening Kit (FISK) has been applied in 35 risk assessment areas in 45 countries across the six inhabited continents (11... 相似文献
9.
10.
Jolanda?HM?van Bilsen Josée?PA?Wagenaar-Hilbers Maarten?JF?van der Cammen Mariska?EA?van Dijk Willem?van Eden Marca?HM?WaubenEmail author 《Arthritis research & therapy》2002,4(4):R2
We have recently found that matrix metalloproteinases (MMPs) are targets for T-cell and B-cell reactivity in experimental
arthritis. In the present article, we investigate whether modulation of MMP-specific T-cell responses could influence the
course of adjuvant arthritis (AA). Lewis rats were treated nasally with MMP peptides prior to or after AA induction. Administration
of the MMP-10 or the MMP-16 peptide prior to AA induction reduced the arthritic symptoms. In contrast, administration of the
MMP-10 peptide after AA induction aggravated the arthritic symptoms. The present study shows the possible usefulness of MMP
peptides for immunotherapy. However, a clear understanding of proper timing of peptide administration is crucial for the development
of such therapies. 相似文献