Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Unique Dimerization Topology and Countercation Binding Modes in 12-Metallacrown-4 Compounds

Seven dimeric metallacrowns (MC) based on Ln[12-MCM(III)N(shi)-4], where LnIII=Dy, Ho, Yb, or Y, MIII=Mn or Ga, and shi3− is salicylhydroximate, have been synthesized and characterized by single-crystal X-ray diffraction, and for the dysprosium-manganese dimers, the magnetic properties have been measured. In each dimer two Ln[12-MCM(III)N(shi)-4] units are linked by four bridging dicarboxylate anions (isophthalate, trimesate, dinicotinate, or 2,2′-dithiodibenzoate). Three different countercations (sodium, gallium(III), or pyridinium) were used to maintain charge balance of the dimer. While pyridinium does not bind to the dimer, the choice of the dicarboxylate dictates where the countercations Na+ or GaIII bind. With isophthalate and trimesate, the sodium ion binds to the central MC cavity opposite of the LnIII, and with dinicotinate the sodium or gallium(III) ions bind to the pyridyl nitrogen of the dinicotinate. All three Dy2Mn8 dimers exhibit an out-of-phase magnetic susceptibility signal consistent with a shallow barrier to magnetization relaxation

Unique Dimerization Topology and Countercation Binding Modes in 12-Metallacrown-4 Compounds

Seven dimeric metallacrowns (MC) based on Ln[12-MCM(III)N(shi)-4], where LnIII=Dy, Ho, Yb, or Y, MIII=Mn or Ga, and shi3− is salicylhydroximate, have been synthesized and characterized by single-crystal X-ray diffraction, and for the dysprosium-manganese dimers, the magnetic properties have been measured. In each dimer two Ln[12-MCM(III)N(shi)-4] units are linked by four bridging dicarboxylate anions (isophthalate, trimesate, dinicotinate, or 2,2′-dithiodibenzoate). Three different countercations (sodium, gallium(III), or pyridinium) were used to maintain charge balance of the dimer. While pyridinium does not bind to the dimer, the choice of the dicarboxylate dictates where the countercations Na+ or GaIII bind. With isophthalate and trimesate, the sodium ion binds to the central MC cavity opposite of the LnIII, and with dinicotinate the sodium or gallium(III) ions bind to the pyridyl nitrogen of the dinicotinate. All three Dy2Mn8 dimers exhibit an out-of-phase magnetic susceptibility signal consistent with a shallow barrier to magnetization relaxation.The structures of seven dimeric heterometallic metallacrowns are described. Each dimer consists of two 12-metallacrown-4 units (ring metals Mn3+ or Ga3+) linked together by dicarboxylate anions (isophthalate, trimesate, dinicotinate, or 2,2′-dithiodibenzoate). Each metallacrown unit also contains one lanthanide ion bound to the central cavity. Lastly, the magnetism of the dysprosium-manganese dimers is examined, and each display slow magnetic relaxation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/175227/1/ejic202200439_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/175227/2/ejic202200439.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/175227/3/ejic202200439-sup-0001-misc_information.pd

Role of nitric oxide signaling components in differentiation of embryonic stem cells into myocardial cells

Nitric oxide (NO) is involved in number of physiological and pathological events. Our previous studies demonstrated a differential expression of NO signaling components in mouse and human ES cells. Here, we demonstrate the effect of NO donors and soluble guanylyl cyclase (sGC) activators in differentiation of ES cells into myocardial cells. Our results with mouse and human ES cells demonstrate an increase in Nkx2.5 and myosin light chain (MLC2) mRNA expression on exposure of cells to NO donors and a decrease in mRNA expression of both cardiac-specific genes with nonspecific NOS inhibitor and a concomitant increase and decrease in the mRNA levels of sGC α1 subunit. Although sGC activators alone exhibited an increase in mRNA expression of cardiac genes (MLC2 and Nkx2.5), robust inductions of mRNA and protein expression of marker genes were observed when NO donors and sGC activators were combined. Measurement of NO metabolites revealed an increase in the nitrite levels in the conditioned media and cell lysates on exposure of cells to the different concentrations of NO donors. cGMP analysis in undifferentiated stem cells revealed a lack of stimulation with NO donors. Differentiated cells however, acquired the ability to be stimulated by NO donors. Although, 3-(4-amino-5-cyclopropylpyrimidin-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo [3,4-b]pyridine (BAY 41-2272) alone was able to stimulate cGMP accumulation, the combination of NO donors and BAY 41-2272 stimulated cGMP levels more than either of the agents separately. These studies demonstrate that cGMP-mediated NO signaling plays an important role in the differentiation of ES cells into myocardial cells