The start of a human life program

正The genetic information of a human being is encoded in the genomic DNA of about 3 billion base pairs.Every new individual starts from a one-cell zygote,or called fertilized egg,carrying genetic and epigenetic information from the parents.The developmental process from one single cell to a whole organism depends on the differential regulation of the genetic information encoded     

Mesoporous silica templated-albumin nanoparticles with high doxorubicin payload for drug delivery assessed with a 3-D tumor cell model

Human serum albumin (HSA) nanoparticles emerge as promising carriers for drug delivery. Among challenges, one important issue is the design of HSA nanoparticles with a low mean size of ca. 50?nm and having a high drug payload. The original strategy developed here is to use sacrificial mesoporous nanosilica templates having a diameter close to 30?nm to drive the protein nanocapsule formation. This new approach ensures first an efficient high drug loading (ca. 30%) of Doxorubicin (DOX) in the porous silica by functionalizing silica with an aminosiloxane layer and then allows the one-step adsorption and the physical cross-linking of HSA by modifying the silica surface with isobutyramide (IBAM) groups. After silica template removal, homogenous DOX-loaded HSA nanocapsules (30–60?nm size) with high drug loading capacity (ca. 88%) are thus formed. Such nanocapsules are shown efficient in multicellular tumor spheroid models (MCTS) of human hepatocarcinoma cells by their significant growth inhibition with respect to controls. Such a new synthesis approach paves the way toward new protein based nanocarriers for drug delivery.     

The Orphan Kinesin PAKRP2 Achieves Processive Motility via a Noncanonical Stepping Mechanism

Phragmoplast-associated kinesin-related protein 2 (PAKRP2) is an orphan kinesin in Arabidopsis thaliana that is thought to transport vesicles along phragmoplast microtubules for cell plate formation. Here, using single-molecule fluorescence microscopy, we show that PAKRP2 is the first orphan kinesin to exhibit processive plus-end-directed motility on single microtubules as individual homodimers. Our results show that PAKRP2 processivity is achieved despite having an exceptionally long (32 residues) neck linker. Furthermore, using high-resolution nanoparticle tracking, we find that PAKRP2 steps via a hand-over-hand mechanism that includes frequent side steps, a prolonged diffusional search of the tethered head, and tight coupling of the ATP hydrolysis cycle to the forward-stepping cycle. Interestingly, truncating the PAKRP2 neck linker to 14 residues decreases the run length of PAKRP2; thus, the long neck linker enhances the processive behavior. Based on the canonical model of kinesin stepping, such a long neck linker is expected to decrease the processivity and disrupt the coupling of ATP hydrolysis to forward stepping. Therefore, we conclude that PAKRP2 employs a noncanonical strategy for processive motility, wherein a long neck linker is coupled with a slow ATP hydrolysis rate to allow for an extended diffusional search during each step without sacrificing processivity or efficiency.     

CD150high Bone Marrow Tregs Maintain Hematopoietic Stem Cell Quiescence and Immune Privilege via Adenosine

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Against expectation: a short sequence with high signal elucidates cone snail phylogeny

A short (259 nucleotide) conserved intronic sequence (CIS) is surprisingly informative for delineating deep phylogenetic relationships in cone snails. Conus species previously have been assigned to clades based on the evidence from mitochondrial 12S and 16S rRNA gene sequences (1129 bp). Despite their length, these genes lack the phylogenetic information necessary to resolve the relationships among the clades. Here we show that the relationships can be inferred from just 46 sites in the very short CIS sequence (a portion of "intron 9" of the γ-glutamyl carboxylase gene). This is counterintuitive because in short sequences sampling error (noise) often drowns out phylogenetic signal. The intron 9 CIS is rich in synapomorphies that define the divergence patterns among eight clades of worm- and fish-hunting Conus, and it contains almost no homoplasy. Parsimony, maximum likelihood and Bayesian analyses of the combined sequences (mt rRNA+CIS) confirm most of the relationships among 23 Conus sequences. This phylogeny implies that fish-hunting behavior evolved at least twice during the history of Conus-once among New World species and independently in the Indo-Pacific clades.