Mechanisms underpinning adaptations in placental calcium transport in normal mice and those with fetal growth restriction

Fetal delivery of calcium, via the placenta, is crucial for appropriate skeletal mineralization. We have previously demonstrated that maternofetal calcium transport, per gram placenta, is increased in the placental specific insulin-like growth factor 2 knockout mouse (P0) model of fetal growth restriction (FGR) compared to wild type littermates (WTL). This effect was mirrored in wild-type (WT) mice comparing lightest vs. heaviest (LvH) placentas in a litter. In both models increased placental calcium transport was associated with normalization of fetal calcium content. Despite this adaptation being observed in small normal (WT), and small dysfunctional (P0) placentas, mechanisms underpinning these changes remain unknown. Parathyroid hormone-related protein (PTHrP), elevated in cord blood in FGR and known to stimulate plasma membrane calcium ATPase, might be important. We hypothesized that PTHrP expression would be increased in LvH WT placentas, and in P0 vs. WTL. We used calcium pathway-focused PCR arrays to assess whether mechanisms underpinning these adaptations in LvH WT placentas, and in P0 vs. WTL, were similar. PTHrP protein expression was not different between LvH WT placentas at E18.5 but trended toward increased expression (139%; P = 0.06) in P0 vs. WTL. PCR arrays demonstrated that four genes were differentially expressed in LvH WT placentas including increased expression of the calcium-binding protein calmodulin 1 (1.6-fold; P < 0.05). Twenty-four genes were differentially expressed in placentas of P0 vs. WTL; significant reductions were observed in expression of S100 calcium binding protein G (2-fold; P < 0.01), parathyroid hormone 1 receptor (1.7-fold; P < 0.01) and PTHrP (2-fold; P < 0.05), whilst serum/glucocorticoid-regulated kinase 1 (SGK1), a regulator of nutrient transporters, was increased (1.4 fold; P < 0.05). Tartrate resistant acid phosphatase 5 (TRAP5 encoded by Acp5) was reduced in placentas of both LvH WT and P0 vs. WTL (1.6- and 1.7-fold, respectively; P < 0.05). Signaling events underpinning adaptations in calcium transport are distinct between LvH placentas of WT mice and those in P0 vs. WTL. Calcium binding proteins appear important in functional adaptations in the former whilst PTHrP and SGK1 are also implicated in the latter. These data facilitate understanding of mechanisms underpinning placental calcium transport adaptation in normal and growth restricted fetuses

A polynomial bound for untangling geometric planar graphs

To untangle a geometric graph means to move some of the vertices so that the resulting geometric graph has no crossings. Pach and Tardos [Discrete Comput. Geom., 2002] asked if every n-vertex geometric planar graph can be untangled while keeping at least n^\epsilon vertices fixed. We answer this question in the affirmative with \epsilon=1/4. The previous best known bound was \Omega((\log n / \log\log n)^{1/2}). We also consider untangling geometric trees. It is known that every n-vertex geometric tree can be untangled while keeping at least (n/3)^{1/2} vertices fixed, while the best upper bound was O(n\log n)^{2/3}. We answer a question of Spillner and Wolff [arXiv:0709.0170 2007] by closing this gap for untangling trees. In particular, we show that for infinitely many values of n, there is an n-vertex geometric tree that cannot be untangled while keeping more than 3(n^{1/2}-1) vertices fixed. Moreover, we improve the lower bound to (n/2)^{1/2}.Comment: 14 pages, 7 figure

Human placental uptake of glutamine and glutamate is reduced in fetal growth restriction

Fetal growth restriction (FGR) is a significant risk factor for stillbirth, neonatal complications and adulthood morbidity. Compared with those of appropriate weight for gestational age (AGA), FGR babies have smaller placentas with reduced activity of amino acid transporter systems A and L, thought to contribute to poor fetal growth. The amino acids glutamine and glutamate are essential for normal placental function and fetal development; whether transport of these is altered in FGR is unknown. We hypothesised that FGR is associated with reduced placental glutamine and glutamate transporter activity and expression, and propose the mammalian target of rapamycin (mTOR) signaling pathway as a candidate mechanism. FGR infants [individualised birth weight ratio (IBR) < 5th centile] had lighter placentas, reduced initial rate uptake of 14C-glutamine and 14C-glutamate (per mg placental protein) but higher expression of key transporter proteins (glutamine: LAT1, LAT2, SNAT5, glutamate: EAAT1) versus AGA [IBR 20th–80th]. In further experiments, in vitro exposure to rapamycin inhibited placental glutamine and glutamate uptake (24 h, uncomplicated pregnancies) indicating a role of mTOR in regulating placental transport of these amino acids. These data support our hypothesis and suggest that abnormal glutamine and glutamate transporter activity is part of the spectrum of placental dysfunction in FGR

CD-independent subsets in meet-distributive lattices

A subset $X$ of a finite lattice $L$ is CD-independent if the meet of any two incomparable elements of $X$ equals 0. In 2009, Cz\'edli, Hartmann and Schmidt proved that any two maximal CD-independent subsets of a finite distributive lattice have the same number of elements. In this paper, we prove that if $L$ is a finite meet-distributive lattice, then the size of every CD-independent subset of $L$ is at most the number of atoms of $L$ plus the length of $L$. If, in addition, there is no three-element antichain of meet-irreducible elements, then we give a recursive description of maximal CD-independent subsets. Finally, to give an application of CD-independent subsets, we give a new approach to count islands on a rectangular board.Comment: 14 pages, 4 figure

Mechanisms Underpinning Adaptations in Placental Calcium Transport in Normal Mice and Those With Fetal Growth Restriction

Fetal delivery of calcium, via the placenta, is crucial for appropriate skeletal mineralization. We have previously demonstrated that maternofetal calcium transport, per gram placenta, is increased in the placental specific insulin-like growth factor 2 knockout mouse (P0) model of fetal growth restriction (FGR) compared to wild type littermates (WTL). This effect was mirrored in wild-type (WT) mice comparing lightest vs. heaviest (LvH) placentas in a litter. In both models increased placental calcium transport was associated with normalization of fetal calcium content. Despite this adaptation being observed in small normal (WT), and small dysfunctional (P0) placentas, mechanisms underpinning these changes remain unknown. Parathyroid hormone-related protein (PTHrP), elevated in cord blood in FGR and known to stimulate plasma membrane calcium ATPase, might be important. We hypothesized that PTHrP expression would be increased in LvH WT placentas, and in P0 vs. WTL. We used calcium pathway-focused PCR arrays to assess whether mechanisms underpinning these adaptations in LvH WT placentas, and in P0 vs. WTL, were similar. PTHrP protein expression was not different between LvH WT placentas at E18.5 but trended toward increased expression (139%; P = 0.06) in P0 vs. WTL. PCR arrays demonstrated that four genes were differentially expressed in LvH WT placentas including increased expression of the calcium-binding protein calmodulin 1 (1.6-fold; P < 0.05). Twenty-four genes were differentially expressed in placentas of P0 vs. WTL; significant reductions were observed in expression of S100 calcium binding protein G (2-fold; P < 0.01), parathyroid hormone 1 receptor (1.7-fold; P < 0.01) and PTHrP (2-fold; P < 0.05), whilst serum/glucocorticoid-regulated kinase 1 (SGK1), a regulator of nutrient transporters, was increased (1.4 fold; P < 0.05). Tartrate resistant acid phosphatase 5 (TRAP5 encoded by Acp5) was reduced in placentas of both LvH WT and P0 vs. WTL (1.6- and 1.7-fold, respectively; P < 0.05). Signaling events underpinning adaptations in calcium transport are distinct between LvH placentas of WT mice and those in P0 vs. WTL. Calcium binding proteins appear important in functional adaptations in the former whilst PTHrP and SGK1 are also implicated in the latter. These data facilitate understanding of mechanisms underpinning placental calcium transport adaptation in normal and growth restricted fetuses

(2-Hydroxy­phenyl­imido-κN)(methano­lato-κO)[2-(2-oxidobenzyl­ideneamino)phenolato-κ2 O,N,O′](triphenyl­phosphine-κP)rhenium(V)

In the neutral title compound, [Re(C6H5NO)(C13H9NO2)(CH3O)(C18H15P)], an 18-valence-electron complex, the ReV ion lies in an octa­hedral coordination geometry with the tridentate dianionic Schiff base 2-(2-oxidobenzyl­idene­amino)phenolate ligand occupying three equatorial coordination sites, and with the triphenyl­phosphine ligand situated trans to the imine N atom. The ReV coordination is completed with a methano­late ligand and a 2-hydroxy­phenyl­imido(2-) ligand. There are two molecules in the asymmetric unit. The crystal structure involves O—H⋯O and C—H⋯O hydrogen bonds. One N and one C atom are disordered over two positions; the site occupancy factors are ca 0.7 and 0.3

Maximum union-free subfamilies

An old problem of Moser asks: how large of a union-free subfamily does every family of m sets have? A family of sets is called union-free if there are no three distinct sets in the family such that the union of two of the sets is equal to the third set. We show that every family of m sets contains a union-free subfamily of size at least \lfloor \sqrt{4m+1}\rfloor - 1 and that this bound is tight. This solves Moser's problem and proves a conjecture of Erd\H{o}s and Shelah from 1972. More generally, a family of sets is a-union-free if there are no a+1 distinct sets in the family such that one of them is equal to the union of a others. We determine up to an absolute multiplicative constant factor the size of the largest guaranteed a-union-free subfamily of a family of m sets. Our result verifies in a strong form a conjecture of Barat, F\"{u}redi, Kantor, Kim and Patkos.Comment: 10 page

Complete genome sequence of the Medicago microsymbiont Ensifer (Sinorhizobium) medicae strain WSM419

Ensifer (Sinorhizobium) medicae is an effective nitrogen fixing microsymbiont of a diverse range of annual Medicago (medic) species. Strain WSM419 is an aerobic, motile, non-spore forming, Gram-negative rod isolated from a M. murex root nodule collected in Sardinia, Italy in 1981. WSM419 was manufactured commercially in Australia as an inoculant for annual medics during 1985 to 1993 due to its nitrogen fixation, saprophytic competence and acid tolerance properties. Here we describe the basic features of this organism, together with the complete genome sequence, and annotation. This is the first report of a complete genome se-quence for a microsymbiont of the group of annual medic species adapted to acid soils. We reveal that its genome size is 6,817,576 bp encoding 6,518 protein-coding genes and 81 RNA only encoding genes. The genome contains a chromosome of size 3,781,904 bp and 3 plasmids of size 1,570,951 bp, 1,245,408 bp and 219,313 bp. The smallest plasmid is a fea-ture unique to this medic microsymbiont