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81.
Justus E Awad D Hohnholt M Schaffran T Edwards K Karlsson G Damian L Gabel D 《Bioconjugate chemistry》2007,18(4):1287-1293
A new class of lipids, containing the closo-dodecaborate cluster, has been synthesized. Two lipids, S-(N, N-(2-dimyristoyloxyethyl)acetamido)thioundecahydro-closo-dodecaborate (2-) (B-6-14) and S-(N, N-(2-dipalmitoyloxyethyl)acetamido)thioundecahydro-closo-dodecaborate (2-) (B-6-16) are described. Both of them have a double-tailed lipophilic part and a headgroup carrying two negative charges. Differential scanning calorimetry shows that B-6-14 and B-6-16 bilayers have main phase transition temperatures of 18.8 and 37.9 degrees C, respectively. Above the transition temperature of 18.8 degrees C, B-6-14 can form liposomal vesicles, representing the first boron-containing lipid with this capability. Upon cooling below the transition temperature, stiff bilayers are formed. When incorporated into liposomal formulations with equimolar amounts of distearoyl phosphatidylcholine (DSPC) and cholesterol, stable liposomes are obtained. The zeta-potential measurements indicate that both B-6-14- and B-6-16-containing vesicles are negatively charged, with the most negative potential described of any liposome so far. The liposomes are of high potential value as transporters of boron to tumor cells in treatments based on boron neutron capture therapy (BNCT). Liposomes prepared from B-6-14 were slightly less toxic in V79 Chinese hamster cells (IC50 5.6 mM) than unformulated Na2B12H11SH (IC50 3.9 mM), while liposomes prepared from B-6-16 were not toxic even at 30 mM. 相似文献
82.
Knowledge of the genetic population structure lies at the heart of mapping studies aiming genes responsible for Mendelian and complex traits. The Quebec population, which is of mostly French descent, is considered an excellent model for such genetic epidemiological endeavours because it is a young founder population. Yet, the assessment of the founder effect has relied mostly on the observed distribution of monogenic diseases and on the analysis of the underlying mutations with investigations focusing on the Saguenay region. To eliminate this clinical bias and to obtain a more complete image of the genetic diversity, different regional populations of Quebec were investigated by analysing neutral markers that represent maternal, paternal and X chromosome lineages. Results indicate that Quebec does not appear more homogeneous nor significantly different from European populations. However, a series of regional founder effects, particularly visible at the level of rare variants, are observed. These effects can be explained by the successive migrations of descendants of the first immigrants from the initial sites of settlement towards the outer regions. Depending on the number of founders and their diversity, as well as on the degree of isolation and the magnitude of the interbreeding with the neighbouring or local populations, such as Amerindians or later migrants, the consequences of these regional founder effects are more or less detectable in the contemporary population. 相似文献
83.
84.
Alesci Marco Smith Rebecca L. Ayala Santacruz Jorge Damian Camperio Ciani Andrea 《Primates; journal of primatology》2022,63(2):161-171
Primates - Increasing urbanisation is encroaching into natural habitats and sometimes forcing wildlife into urban centres. Whether or not wildlife can thrive in an urban environment is dependent on... 相似文献
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86.
Mark Schaller Damian R. Murray Adrian Bangerter 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2015,370(1669)
The ‘behavioural immune system’ is composed of mechanisms that evolved as a means of facilitating behaviours that minimized infection risk and enhanced fitness. Recent empirical research on human populations suggests that these mechanisms have unique consequences for many aspects of human sociality—including sexual attitudes, gregariousness, xenophobia, conformity to majority opinion and conservative sociopolitical attitudes. Throughout much of human evolutionary history, these consequences may have had beneficial health implications; but health implications in modern human societies remain unclear. This article summarizes pertinent ways in which modern human societies are similar to and different from the ecologies within which the behavioural immune system evolved. By attending to these similarities and differences, we identify a set of plausible implications—both positive and negative—that the behavioural immune system may have on health outcomes in contemporary human contexts. We discuss both individual-level infection risk and population-level epidemiological outcomes. We also discuss a variety of additional implications, including compliance with public health policies, the adoption of novel therapeutic interventions and actual immunological functioning. Research on the behavioural immune system, and its implications in contemporary human societies, can provide unique insights into relationships between fitness, sociality and health. 相似文献
87.
Serena C. Hedgepeth M. Iveth Garcia Larry E. Wagner II Ana M. Rodriguez Sree V. Chintapalli Russell R. Snyder Gary D. V. Hankins Beric R. Henderson Kirsty M. Brodie David I. Yule Damian B. van Rossum Darren Boehning 《The Journal of biological chemistry》2015,290(11):7304-7313
The inositol 1,4,5-trisphosphate receptor (IP3R) is a ubiquitously expressed endoplasmic reticulum (ER)-resident calcium channel. Calcium release mediated by IP3Rs influences many signaling pathways, including those regulating apoptosis. IP3R activity is regulated by protein-protein interactions, including binding to proto-oncogenes and tumor suppressors to regulate cell death. Here we show that the IP3R binds to the tumor suppressor BRCA1. BRCA1 binding directly sensitizes the IP3R to its ligand, IP3. BRCA1 is recruited to the ER during apoptosis in an IP3R-dependent manner, and, in addition, a pool of BRCA1 protein is constitutively associated with the ER under non-apoptotic conditions. This is likely mediated by a novel lipid binding activity of the first BRCA1 C terminus domain of BRCA1. These findings provide a mechanistic explanation by which BRCA1 can act as a proapoptotic protein. 相似文献
88.
p53 Modulates Notch Signaling in MCF‐7 Breast Cancer Cells by Associating With the Notch Transcriptional Complex Via MAML1 下载免费PDF全文
Jieun Yun Ingrid Espinoza Antonio Pannuti Damian Romero Luis Martinez Mary Caskey Adina Stanculescu Maurizio Bocchetta Paola Rizzo Vimla Band Hamid Band Hwan Mook Kim Song‐Kyu Park Keon Wook Kang Maria Laura Avantaggiati Christian R. Gomez Todd Golde Barbara Osborne Lucio Miele 《Journal of cellular physiology》2015,230(12):3115-3127
89.
Ecological niche breadth and microhabitat guild structure in temperate Australian reptiles: Implications for natural resource management in endangered grassy woodland ecosystems 下载免费PDF全文
Damian R. Michael Geoffrey M. Kay Mason Crane Daniel Florance Christopher MacGregor Sachiko Okada Lachlan McBurney David Blair David B. Lindenmayer 《Austral ecology》2015,40(6):651-660
Ecological theory predicts that species with narrow niche requirements (habitat specialists) are more vulnerable to anthropocentric disturbances than those with broad niche requirements (habitat generalists). Hence, understanding a species ecological niche and guild membership would serve as a valuable management tool for providing a priori assessments of a species extinction risk. It also would help to forecast a species capacity to respond to land use change, as what might be expected to occur under financial incentive schemes to improve threatened ecological vegetation communities. However, basic natural history information is lacking for many terrestrial species, particularly reptiles in temperate regions of the world. To overcome this limitation, we collated 3527 reptile observations from 52 species across an endangered woodland ecoregion in south‐eastern Australia and examined ecological niche breadth and microhabitat guild structure. We found 30% of species had low ecological niche values and were classified as habitat specialists associated with large eucalypt trees, woody debris, surface rock or rocky outcrops. Cluster analysis separated species into six broad guilds based on microhabitat similarity. Approximately 80% of species belonged to guilds associated with old growth vegetation attributes or non‐renewable litho‐resources such as surface rock or rocky outcrops. Our results suggest that agri‐environment schemes that focus purely on grazing management are unlikely to provide immediate benefits to broad suites of reptiles associated with old growth vegetation and litho‐resources. Our classification scheme will be useful for identifying reptile species that are potentially vulnerable to anthropocentric disturbances and may require alternative strategies for improving habitat suitability and reptile conservation outcomes in grassy woodland ecosystems. 相似文献
90.
Autotaxin (ATX) is an attractive target for the anticancer therapeutics that inhibits angiogenesis, invasion and migration. ATX is an extracellular lysophospholipase D that hydrolyzes lysophosphatidylcholine to form the bioactive lipid lysophosphatidic acid. The aromatic phosphonate S32826 was the first described nanomolar inhibitor of ATX. However, the tridecylamide substituent on aromatic ring contributed to its poor solubility and bioavailability, severely limiting its utility in vivo. c Log P calculations revealed that the lipophilicity of S32826 could be lowered by shortening its hydrophobic chain and by introducing substituents alpha to the phosphonate. Herein, we describe the synthesis of a small set of α-substituted phosphonate analogs of S32826, and we show that shortening the chain and adding α-halo or α-hydroxy substituents increased solubility; however, ATX inhibition was reduced by most substitutions. An optimal compound was identified for examination of biological effects of ATX inhibition in vivo. 相似文献