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"ADAMS, M. D"
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Freshwater Sponges Have Functional, Sealing Epithelia with High Transepithelial Resistance and Negative Transepithelial Potential
Epithelial tissue - the sealed and polarized layer of cells that regulates transport of ions and solutes between the environment and the internal milieu - is a defining characteristic of the Eumetazoa. Sponges, the most ancient metazoan phylum, are generally believed to lack true epithelia, but their ability to occlude passage of ions has never been tested. Here we show that freshwater sponges (Demospongiae, Haplosclerida) have functional epithelia with high transepithelial electrical resistance (TER), a transepithelial potential (TEP), and low permeability to small-molecule diffusion. Curiously, the Amphimedon queenslandica sponge genome lacks the classical occluding genes [5] considered necessary to regulate sealing and control of ion transport. The fact that freshwater sponge epithelia can seal suggests that either occluding molecules have been lost in some sponge lineages, or demosponges use novel molecular complexes for epithelial occlusion; if the latter, it raises the possibility that mechanisms for occlusion used by sponges may exist in other metazoa. Importantly, our results imply that functional epithelia evolved either several times, or once, in the ancestor of the Metazoa.
Journal Article
في جوف النكتة : الفكاهة لعكس هندسة العقل
الفكاهة تقف خلف أسئلة حول ما نضحك لأجله لماذا نرى الطرفة القديمة وكأنها موضة قديمة ؟ كيف تاثرت الفكاهة بالتطور ؟ النكتة لها جوف، وفي كل مرة ستخدم غرضا ما، إذ تتعدد أغراضها وبالطبع لن تنجح النكتة المغشوشة ! فإما أن تضحك لها، أو أن لا تتفاعل معها. يفكك هذا الكتاب الفكاهة وعلاقتها بالأدراك ويكشف أدوارا تلعبها الفكاهة في حياتنا اليومية ربما لم ننتبه لها بالاصل، وربما لم لكن نعرف أنها نابعة من الفكاهة الضحك المعدي والفكاهة الإدراكية، كلها مواضيع ساخنة ترتبط بالتطور والنظرية الداروينية التي انطلقت كسفينة لا يمكن إيقافها طالما توفرت رياح المعرفة وتوفر السؤال الصحيح.
Book
Chromosome 2 Sequence of the Human Malaria Parasite Plasmodium falciparum
Chromosome 2 of Plasmodium falciparum was sequenced; this sequence contains 947,103 base pairs and encodes 210 predicted genes. In comparison with the Saccharomyces cerevisiae genome, chromosome 2 has a lower gene density, introns are more frequent, and proteins are markedly enriched in nonglobular domains. A family of surface proteins, rifins, that may play a role in antigenic variation was identified. The complete sequencing of chromosome 2 has shown that sequencing of the A + T-rich P. falciparum genome is technically feasible.
Journal Article
Superman : President Luthor
His fame bolstered after helping to rebuild Gotham City after an earthquake, billionaire Lex Luthor decides to run for the highest office in the land, the American presidency.
Book
Characterizing the Developmental Trajectory of Sirolimus Clearance in Neonates and Infants
Sirolimus is increasingly being used in neonates and infants, but the mechanistic basis of age‐dependent changes in sirolimus disposition has not been fully addressed yet. In order to characterize the age‐dependent changes, serial sirolimus clearance (CL) estimates in individual young pediatric patients were collected and analyzed by population modeling analysis. In addition, sirolimus metabolite formation was also investigated to further substantiate the corresponding age‐dependent change in CYP3A activity. The increasing pattern over time of allometrically size‐normalized sirolimus CL estimates vs. age was well described by a sigmoidal Emax model. This age‐dependent increase was also observed within each individual patient over a 4‐year study period. CYP3A‐dependent sirolimus metabolite formation changed in a similar fashion. This study clearly demonstrates the rapid increase of sirolimus CL over time in neonates and infants, indicating the developmental change. This developmental pattern can be explained by a parallel increase in CYP3A metabolic activity.
Journal Article
Whole-Genome Random Sequencing and Assembly of Haemophilus Influenzae Rd
An approach for genome analysis based on sequencing and assembly of unselected pieces of DNA from the whole chromosome has been applied to obtain the complete nucleotide sequence (1,830, 137 base pairs) of the genome from the bacterium Haemophilus influenzae Rd. This approach eliminates the need for initial mapping efforts and is therefore applicable to the vast array of microbial species for which genome maps are unavailable. The H. influenzae Rd genome sequence (Genome Sequence DataBase accession number L42023) represents the only complete genome sequence from a free-living organism.
Journal Article
Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi
The genome of the bacterium
Borrelia burgdorferi
B31, the aetiologic agent of Lyme disease, contains a linear chromosome of 910,725 base pairs and at least 17 linear and circular plasmids with a combined size of more than 533,000 base pairs. The chromosome contains 853 genes encoding a basic set of proteins for DNA replication, transcription, translation, solute transport and energy metabolism, but, like
Mycoplasma genitalium
, it contains no genes for cellular biosynthetic reactions. Because
B. burgdorferi
and
M. genitalium
are distantly related eubacteria, we suggest that their limited metabolic capacities reflect convergent evolution by gene loss from more metabolically competent progenitors. Of 430 genes on 11 plasmids, most have no known biological function; 39% of plasmid genes are paralogues that form 47 gene families. The biological significance of the multiple plasmid-encoded genes is not clear, although they may be involved in antigenic variation or immune evasion.
Journal Article
The Minimal Gene Complement of Mycoplasma genitalium
The complete nucleotide sequence (580,070 base pairs) of the Mycoplasma genitalium genome, the smallest known genome of any free-living organism, has been determined by whole-genome random sequencing and assembly. A total of only 470 predicted coding regions were identified that include genes required for DNA replication, transcription and translation, DNA repair, cellular transport, and energy metabolism. Comparison of this genome to that of Haemophilus influenzae suggests that differences in genome content are reflected as profound differences in physiology and metabolic capacity between these two organisms.
Journal Article
Development of a Pediatric Physiologically Based Pharmacokinetic Model for Sirolimus: Applying Principles of Growth and Maturation in Neonates and Infants
This study describes the maturation of sirolimus clearance in a cohort of very young pediatric patients with vascular anomalies. The relationship between allometrically scaled in vivo clearance and age was described by the Emax model in patients aged 1 month to 2 years. Consistent with the observed increase, in vitro intrinsic clearance of sirolimus using pediatric liver microsomes showed a similar age‐dependent increase. In children older than 2 years, allometrically scaled sirolimus clearance did not show further maturation. Simulated clearance estimates with a sirolimus physiologically based pharmacokinetic model that included CYP3A4/5/7 and CYP2C8 maturation profiles were in close agreement with observed in vivo clearance values. In addition, physiologically based pharmacokinetic model‐simulated sirolimus pharmacokinetic profiles predicted the actual observations well. These results demonstrate the utility of a physiologically based pharmacokinetic modeling approach for the prediction of the developmental trajectory of sirolimus metabolic activity and its effects on total body clearance in neonates and infants. CPT Pharmacometrics Syst. Pharmacol. (2015) 4, 127–134; doi:10.1038/psp4.17; published online on 4 February 2015.
Journal Article