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Using a cross-sectional comparison group design, 4,746 ethnically diverse middle and high school students from 31 public schools in a metropolitan area were surveyed about their health, emotional factors (self-esteem, depressive symptoms, and suicidality), and behaviors (tobacco, alcohol, and drug use). Based on regression analyses that adjusted for gender, race, school level, and socioeconomic status, adolescents with chronic health conditions were significantly more likely to report depressive symptoms and low self-esteem than adolescents without chronic health conditions; they were almost twice as likely to have considered suicide and over 31/2 times more likely to have attempted suicide. They also reported greater use of cigarettes, marijuana, and illicit drugs. Given the extent of behavioral and emotional problems among adolescents with chronic health conditions, appropriate referrals and mental health services for these adolescents are warranted. [ABSTRACT FROM AUTHOR]

The authors investigated the possible association between a mother's nausea during pregnancy and her child's risk for a congenital heart defect using data from the population-based Atlanta Birth Defects Case-Control Study conducted in 1982-1983. Case infants (n = 998) had nonsyndromic congenital heart defects and control infants (n = 3,029) had no congenital defects. Nausea during pregnancy (NP) was graded in eight levels of 'severity' based on its onset, frequency, and duration. Level 1, the most severe NP, was associated with a lower risk for a congenital heart defect in the child (odds ratio (OR) = 0.81, 95% confidence interval (CI) 0.67-0.99) compared with no nausea. The lower risk tended to disappear with less severe levels of nausea, and the trend was statistically significant. Overall, early NP (levels 1 to 4 combined) with use of antinausea medication, particularly Bendectin (doxylamine, dicyclomine (dropped from the formulation in 1976), pyridoxine (vitamin B6)), was associated with a lower risk for congenital heart defects compared with: 1) absence of nausea (OR = 0.67, 95% CI 0.50-0.92), and 2) nausea without medication use (OR = 0.70, 95% CI 0.50-0.94). The results suggest that pregnancy hormones and factors or, alternatively, a component of Bendectin (most probably pyridoxine) may be important for normal heart development. These findings outline potential areas for future research on and prevention of congenital heart defects. [ABSTRACT FROM AUTHOR]

Spina bifida and anencephaly are serious birth defects. To reduce the occurrence of these birth defects, the Food and Drug Administration authorized the fortification of all enriched cereal grain products with folic acid in March 1996, with compliance mandatory by January 1998. This report reviews data reported to CDC's National Center for Health Statistics (NCHS) regarding spina bifida and anencephaly prevalence for live births in the United States during 199--2001. Since 1989, NCHS has compiled birth defect data from checkboxes that appear on birth certificates. For consistency in trends, this report uses data for 199--2001 from all U.S. reporting areas except Maryland, New Mexico, and New York. Data for 2001 are preliminary. During1996-2001, a 23% decline occurred in neural tube defects (spina bifida and anencephaly combined). Spina bifida declined 24% during this period, and anencephaly declined 21%. The United States has experienced declines in spina bifida and anencephaly cases since folic acid fortification of all enriched cereal grain products. The observed declines have translated into approximately 920 infants being born without these serious defects each year. Continued monitoring of the occurrence of spina bifida and anencephaly will be necessary to evaluate the effectiveness of folic acid fortification. [ABSTRACT FROM AUTHOR]

Background: Folic acid supplements are recommended for women of childbearing age to prevent neural tube defects in their offspring. Results of some studies, however, suggest an increase in multiple births associated with use of vitamin supplements that contain folic acid during pregnancy. Our aim was to assess this association.Methods: We used data from a population-based cohort study from which we assessed the occurrence of multiple births in women (n=242015) who had participated in a campaign to prevent neural tube defects with folic acid supplements (400 microg per day) in China. Folic acid use was ascertained before pregnancy outcome was known. We studied the relation between multiple births and any use of folic acid pills before or during early pregnancy; additionally, we investigated mechanisms by which folic acid could potentially affect the occurrence of multiple births by examining pill-taking at three time periods: before ovulation, around the time of fertilisation, and after conception.Findings: 1496 (0.62%) multiple births occurred in a cohort of 242015 women who had registered with the study between October, 1993, and September, 1995, and who had a pregnancy not affected by a birth defect; the rate of multiple births in women who did and did not take folic acid before or during early pregnancy was 0.59% and 0.65%, respectively (rate ratio 0.91; 95% CI 0.82-1.00).Interpretation: Our findings suggest that consumption of folic acid supplements during pregnancy is not associated with an increased occurrence of multiple births. [ABSTRACT FROM AUTHOR]

Background: Although taking supplements that contain 400 microg of folic acid before and during early pregnancy reduces a woman's risk for having a baby with a neural-tube defect (NTD), the effects of such supplements on other pregnancy outcomes remain unclear. We examined whether the use of such supplements affects the occurrence of miscarriage.Methods: Participants were women in China who had taken part in a recent folic acid campaign to prevent NTDs and who had registered in this campaign before they became pregnant for the first time. We examined the risk for miscarriage among women who had confirmed pregnancies and who had or had not taken pills containing only 400 microg of folic acid before and during early pregnancy.Results: The overall rate of miscarriage was 9.1% (2155/23806). The rates of miscarriage among women who had and had not taken folic acid pills before and during the first trimester were 9.0% and 9.3%, respectively (risk ratio 0.97 [95% CI 0.84-1.12]). The distributions of gestational age at pregnancy diagnosis and at miscarriage were similar for both groups of women.Interpretation: In this population-based study of a cohort of women whose use of folic acid supplements while pregnant had been previously documented and who had been pregnant for the first time, we found no evidence that daily consumption of 400 microg of folic acid before and during early pregnancy influenced their risk for miscarriage. [ABSTRACT FROM AUTHOR]

Background: Riluzole exhibits neuroprotective and therapeutic effects in several neurological disease models associated with excessive synaptic glutamate (Glu) release. We recently showed riluzole prevents acute excitotoxic hippocampal neural injury at 3 days in the kainic acid (KA) model of temporal lobe epilepsy (TLE). Currently, it is unknown if preventing acute neural injury and the neuroinflammatory response is sufficient to suppress epileptogenesis., Methods: The KA rat model of TLE was used to determine if riluzole attenuates acute hippocampal neural injury and reactive gliosis. KA was administered to adult male Sprague-Dawley (250 g) rats at 5 mg/kg/hr until status epilepticus (SE) was observed, and riluzole was administered at 10 mg/kg 1 h and 4 h after SE and once per day for the next 2 days. Immunostaining was used to assess neural injury (FJC and NeuN), microglial activation (Iba1 and ED-1/CD68) and astrogliosis (GFAP and vimentin) at day 7 and day 14 after KA-induced SE. Learning and memory tests (Y-maze, Novel object recognition test, Barnes maze), behavioral hyperexcitability tests, and spontaneous generalized recurrent seizure (SRS) activity (24-hour video monitoring) were assessed at 11-15 weeks., Results: Here we show that KA-induced hippocampal neural injury precedes the neuroimmune response and that riluzole attenuates acute neural injury, microglial activation, and astrogliosis at 7 and 14 days. We find that reducing acute hippocampal injury and the associated neuroimmune response following KA-induced SE by riluzole attenuates hippocampal-dependent cognitive impairment, behavioral hyperexcitability, and tonic/clonic generalized SRS activity after 3 months. We also show that riluzole attenuates SE-associated body weight loss during the first week after KA-induced SE., Discussion: Riluzole acts on multiple targets that are involved to prevent excessive synaptic Glu transmission and excitotoxic neuronal injury. Attenuating KA-induced neural injury and subsequent microglia/astrocyte activation in the hippocampus and extralimbic regions with riluzole reduces TLE-associated cognitive deficits and generalized SRS and suggests that riluzole could be a potential antiepileptogenic drug., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Kyllo, Allocco, Hei, Wulff and Erickson.)

β-Carbon eliminations of aryl, allylic, and propargylic alkoxides of Rh(i), Pd(ii), and Cu(i) are key elementary reactions in the proposed mechanisms of homogeneously catalysed cross-coupling, group transfer, and annulation. Besides the handful of studies with isolable Rh(i)-alkoxides, β-carbon eliminations of Pd(ii)- and Cu(i)-alkoxides are less definitive. Herein, we provide a comprehensive synthetic, structural, and mechanistic study on the β-alkynyl eliminations of isolable secondary and tertiary propargylic alkoxide Cu(i) complexes, LCuOC(H)(Ph)C[triple bond, length as m-dash]CPh and LCuOC(Ar F ) 2 C[triple bond, length as m-dash]CPh (L = N-heterocyclic carbene (NHC), dppf, S -BINAP), to produce monomeric (NHC)CuC[triple bond, length as m-dash]CPh, dimeric [(diphosphine)CuC[triple bond, length as m-dash]CPh] 2 , and the corresponding carbonyl. Selective β-alkynyl over β-hydrogen elimination was observed for NHC- and diphosphine-supported secondary propargylic alkoxide complexes. The mechanism for the first-order reaction of β-carbon elimination of (IPr*Me)CuOC(Ar F ) 2 C[triple bond, length as m-dash]CPh is proposed to occur through an organized four-centred transition state via a Cu-alkyne π complex based on Eyring analysis of variable-temperature reaction rates by UV-vis kinetic analysis to provide Δ H ‡ = 24(1) kcal mol -1 , Δ S ‡ = -8(3) e.u., and Δ G ‡ (25 °C) = 27 kcal mol -1 over a temperature range of 60-100 °C. Additional quantitative UV-vis kinetic studies conclude that the electronic and steric properties of the NHC ligands engendered a marginal effect on the elimination rate, requiring 2-3 h at 100 °C for completion, whereas complete β-alkynyl eliminations of diphosphine-supported propargylic alkoxides were observed in 1-2 h at 25 °C., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A series of thiosemicarbazonato-hydrazinatopyridine zinc(II) complexes were evaluated as direct air CO 2 capture agents. The complexes sequester CO 2 in a methanol solution as a metal-coordinated methylcarbonate. The reaction is reversible upon sparging of solutions with an inert gas (N 2 or Ar). The capture process involves metal-ligand cooperativity with the noncoordinating nitrogen of the hydrazinatopyridine functional group serving as a Brønsted-Lowry base and the zinc acting as a Lewis acid. In this study, the pendent amine of the thiosemicarbazonato group was varied to include 4-phenyl (ZnL 5 ), 4-(trifluoromethyl)phenyl (ZnL 6 ), 4-cyanophenyl (ZnL 7 ), 4-tolyl (ZnL 8 ), and 4-naphthyl (ZnL 9 ). Hyperconjugation between the pendent group and the ligand core resulted in modulation of the metal ion acidity, as quantified by ligand exchange equilibrium constants ( K 3 = 193-511) and ligand basicity (p K a,MeOH = 11.09-11.94). Variations in electronic structure that decreased ligand basicity were more than offset by increases in Lewis acidity. The equilibrium constant ( K 1 ) for CO 2 capture varied from 46300 to 73700. Overall, the value of K 1 was directly related to the relative Lewis acidity of the complexes ( K 3 ). Notably, there was an overall inverse relationship between K 1 and the ligand basicity. The results provide insights into ligand design to further improve CO 2 capture.

Obtaining the complex refractive index vectors n ( ν ~) and k ( ν ~) allows calculation of the (infrared) reflectance spectrum that is obtained from a solid in any of its many morphological forms. We report an adaptation to the KBr pellet technique using two gravimetric dilutions to derive quantitative n ( ν ~)/ k ( ν ~) for dozens of powders with greater repeatability. The optical constants of bisphenol A and sucrose are compared to those derived by other methods, particularly for powdered materials. The variability of the k values for bisphenol A was examined by 10 individual measurements, showing an average coefficient of variation for k peak heights of 5.6%. Though no established standards exist, the pellet-derived k peak values of bisphenol A differ by 11% and 31% from their single-angle- and ellipsometry-derived values, respectively. These values provide an initial estimate of the precision and accuracy of complex refractive indices that can be derived using this method. Limitations and advantages of the method are discussed, the salient advantage being a more rapid method to derive n / k for those species that do not readily form crystals or specular pellets.

High affinity methylaminoisobutyric acid(MeAIB)/glutamine(Gln) transport activity regulated by neuronal firing occurs at the plasma membrane in mature rat hippocampal neuron-enriched cultures. Spontaneous Ca 2+ -regulated transport activity was similarly inhibited by riluzole, a benzothiazole anticonvulsant agent, and by novel naphthalenyl substituted aminothiazole derivatives such as SKA-378. Here, we report that spontaneous transport activity is stimulated by 4-aminopyridine (4-AP) and that phorbol-myristate acetate (PMA) increases high K + stimulated transport activity that is inhibited by staurosporine. 4-AP-stimulated spontaneous and PMA-stimulated high K + -induced transport is not present at 7 days in vitro (DIV) and is maximal by DIV∼21. The relative affinity for MeAIB is similar for spontaneous and high K + -stimulated transport (K m  ∼ 50 μM) suggesting that a single transporter is involved. While riluzole and SKA-378 inhibit spontaneous transport with equal potency (IC 50 ∼ 1 μM), they exhibit decreased (∼3-5 X) potency for 4-AP-stimulated spontaneous transport. Interestingly, high K + -stimulated MeAIB transport displays lower and differential sensitivity to the two compounds. SKA-378-related halogenated derivatives of SKA-75 (SKA-219, SKA-377 and SKA-375) preferentially inhibit high K + -induced expression of MeAIB transport activity at the plasma membrane (IC 50  < 25 μM), compared to SKA-75 and riluzole (IC 50  > 100 μM). Ca 2+ -dependent spontaneous and high K + -stimulated MeAIB transport activity is blocked by ω-conotoxin MVIIC, ω-agatoxin IVA, ω-agatoxin TK (IC 50 ∼ 500 nM) or cadmium ion (IC 50 ∼ 20 μM) demonstrating that P/Q-type Ca V channels that are required for activity-regulated presynaptic vesicular glutamate (Glu) release are also required for high-affinity MeAIB transport expression at the plasma membrane. We suggest that neural activity driven and Ca 2+ dependent trafficking of the high affinity MeAIB transporter to the plasma membrane is a unique target to understand mechanisms of Glu/Gln recycling in synapses and acute neuroprotection against excitotoxic presynaptic Glu induced neural injury., Competing Interests: The authors have no conflict of interests., (© 2023 The Authors.)

Mutant B.4.1 , generated via EMS mutagenesis in Drosophila melanogaster , was studied by undergraduate students participating in the Fly-CURE. After inducing genetically mosaic tissue in the adult eye, B.4.1 mutant tissue displays a robust increase in cell division and a rough appearance. Complementation mapping and sequence analysis identified a nonsense mutation in the gene CG1603 , which we named clifford ( cliff ) due to observed increases in red-pigmented mutant tissue compared to controls. cliff encodes a zinc finger-containing protein implicated in transcriptional control. RNAi knockdown of cliff similarly results in rough eyes, confirming a role for Cliff in eye development., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2023 by the authors.)

Mechanistic studies of substrate insertion into dimeric [(NHC)CuH] 2 (NHC=N-heterocyclic carbene) complexes with two bridging hydrides have been shown to require dimer dissociation to generate transient, highly reactive (NHC)Cu-H monomers in solution. Using single-crystal to single-crystal (SC-SC) transformations, we discovered a new pathway of stepwise insertion of CO 2 into [(NHC)CuH] 2 without complete dissociation of the dimer. The first CO 2 insertion into dimeric [(IPr*OMe)CuH] 2 (IPr*OMe=N,N'-bis(2,6-bis(diphenylmethyl)-4-methoxy-phenyl)imidazole-2-ylidene) produced a dicopper formate hydride [(IPr*OMe)Cu] 2 (μ-1,3-O 2 CH)(μ-H). A second CO 2 insertion produced a dicopper bis(formate), [(IPr*OMe)Cu] 2 (μ-1,3-O 2 CH)(μ-1,1-O 2 CH), containing two different bonding modes of the bridging formate. These dicopper formate complexes are inaccessible from solution reactions since the dicopper core cleanly ruptures to monomeric complexes when dissolved in a solvent., (© 2023 The Authors. Published by Wiley-VCH GmbH.)

Epileptogenic seizures, or status epilepticus (SE), leads to excitotoxic injury in hippocampal and limbic neurons in the kainic acid (KA) animal model of temporal lobe epilepsy (TLE). Here, we have further characterized neural activity regulated methylaminoisobutryic acid (MeAIB)/glutamine transport activity in mature rat hippocampal neurons in vitro that is inhibited by riluzole (IC 50  = 1 μM), an anti-convulsant benzothiazole agent. We screened a library of riluzole derivatives and identified SKA-41 followed by a second screen and synthesized several novel chlorinated aminothiazoles (SKA-377, SKA-378, SKA-379) that are also potent MeAIB transport inhibitors in vitro, and brain penetrant following systemic administration. When administered before KA, SKA-378 did not prevent seizures but still protected the hippocampus and several other limbic areas against SE-induced neurodegeneration at 3d. When SKA-377 - 379, (30 mg/kg) were administered after KA-induced SE, acute neural injury in the CA3, CA1 and CA4/hilus was also largely attenuated. Riluzole (10 mg/kg) blocks acute neural injury. Kinetic analysis of SKA-378 and riluzoles' blockade of Ca 2+ -regulated MeAIB transport in neurons in vitro indicates that inhibition occurs via a non-competitive, indirect mechanism. Sodium channel Na V 1.6 antagonism blocks neural activity regulated MeAIB/Gln transport in vitro (IC 50  = 60 nM) and SKA-378 is the most potent inhibitor of Na V 1.6 (IC 50  = 28 μM) compared to Na V 1.2 (IC 50  = 118 μM) in heterologous cells. However, pharmacokinetic analysis suggests that sodium channel blockade may not be the predominant mechanism of neuroprotection here. Riluzole and our novel aminothiazoles are agents that attenuate acute neural hippocampal injury following KA-induced SE and may help to understand mechanisms involved in the progression of epileptic disease., Competing Interests: Declaration of competing interest The authors have no conflict of interests., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The ability of Cu-H complexes to undergo selective insertion of unsaturated hydrocarbons under mild conditions has rendered them valuable, versatile catalysts. The direct formation of Cu allyl intermediates from unfunctionalized 1,3-dienes and transient Cu hydrides is an appealing strategy for upgrading conjugated diene feedstocks. However, empirical mechanistic studies of the underlying elementary steps and characterization of key intermediates in Cu-H catalysis are sparse. Using [(NHC)CuH] 2 (NHC = N -heterocyclic carbene), we examined the steric effects of NHC ligands on two key elementary steps of CuH-catalyzed carbonyl allylation: the insertion of a diene into the Cu-H bond to produce a Cu-allyl complex, and the formation of C-C bonds from stoichiometric allylations of ketones and aldehydes. The resulting allyl and homoallylic alkoxide complexes have been characterized by NMR spectroscopy and single-crystal X-ray diffraction. Employing isolable (NHC)Cu-allyl complexes, we further evaluated the roles of the ligand size, electronic properties of carbonyl substrates, coordinating groups within the substrate, and solvent on the regioselectivity, diastereoselectivity, and relative rate of the C-C bond formation step. In contrast to the clean allylation of ketones, allylation of aldehydes provided a rare example of a formal β-hydride elimination reaction from a secondary homoallylic alkoxide species. Mechanistic studies of key elementary steps provide insights for a range of catalytic reactions of dienes mediated by hydride complexes.

An unusual diastereodivergent stereoselective allylation reaction is presented. It consists of a palladium-catalyzed allylation reaction of an organocatalytically generated amino isobenzofulvene, where the diastereoselectivity is controlled by the electronic properties of a monodentate, achiral ligand on palladium. One major diastereoisomer is formed using triarylphosphines substituted with neutral or electron-donating substituents of the aryl group, while those with electron-withdrawing substituents favor the other diastereoisomer. The diastereoselectivity correlates with the Taft inductive parameter of substituents on the triarylphosphine ligand on palladium. The synergistic reaction involves both a catalytic secondary amine catalyst for the indene-aldehyde activation and the monodentate phosphine ligands on palladium, affording a highly enantioselective reaction with up to 98 % enantiomeric excess. Based on computational investigations, the role of the monodentate phosphine ligand on the diastereoselectivity is discussed., (© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Transient Cu-H monomers have long been invoked in the mechanisms of substrate insertion in Cu-H catalysis. Their role from Cu-H aggregates has been mostly inferred since ligands to stabilize these monomeric intermediates for systematic studies remain limited. Within the last decade, new sterically demanding N -heterocyclic carbene (NHC) ligands have led to isolable Cu-H dimers and, in some cases, spectroscopic characterization of Cu-H monomers in solution. We report an NHC ligand, IPr*R, containing para R groups of CHPh 2 and CPh 3 on the ligand periphery for the isolation of a Cu-H monomer for insertion of internal alkenes. This reactivity has not been reported for (NHC)CuH complexes despite their common application in Cu-H-catalyzed hydrofunctionalization. Changing from CHPh 2 to CPh 3 impacts the relative concentration of Cu-H monomers, rate of alkene insertion, and reaction of a trisubstituted internal alkene. Specifically, for R = CPh 3 , monomeric (IPr*CPh 3 )CuH was isolated and provided >95% monomer (10 mM in C 6 D 6 ). In contrast, for R = CHPh 2 , solutions of [(IPr*CHPh 2 )CuH] 2 are 80% dimer and 20% (IPr*CHPh 2 )CuH monomer at 25 °C based on 1 H, 13 C, and 1 H- 13 C HMBC NMR spectroscopy. Quantitative 1 H NMR kinetic studies on cyclopentene insertion into Cu-H complexes to form the corresponding Cu-cyclopentyl complexes demonstrate a strong dependence on the rate of insertion and concentration of the Cu-H monomer. Only (IPr*CPh 3 )CuH, which has a high monomer concentration, underwent regioselective insertion of a trisubstituted internal alkene, 1-methylcyclopentene, to give (IPr*CPh 3 )Cu(2-methylcyclopentyl), which has been crystallographically characterized. We also demonstrated that (IPr*CPh 3 )CuH catalyzes the hydroboration of cyclopentene and methylcyclopentene with pinacolborane.

Most ligand designs for reactions catalyzed by (NHC)Cu-H (NHC = N-heterocyclic carbene ligand) have focused on introducing steric bulk near the Cu center. Here, we evaluate the effect of remote ligand modification in a series of [(NHC)CuH] 2 in which the para substituent (R) on the N -aryl groups of the NHC is Me, Et, t Bu, OMe or Cl. Although the R group is distant (6 bonds away) from the reactive Cu center, the complexes have different spectroscopic signatures. Kinetics studies of the insertion of ketone, aldimine, alkyne, and unactivated α-olefin substrates reveal that Cu-H complexes with bulky or electron-rich R groups undergo faster substrate insertion. The predominant cause of this phenomenon is destabilization of the [(NHC)CuH] 2 dimer relative to the (NHC)Cu-H monomer, resulting in faster formation of Cu-H monomer. These findings indicate that remote functionalization of NHCs is a compelling strategy for accelerating the rate of substrate insertion with Cu-H species., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Vesicular glutamate transporters (VGLUTs) control quantal size of glutamatergic transmission and have been the center of numerous studies over the past two decades. VGLUTs contain two independent transport modes that facilitate glutamate packaging into synaptic vesicles and phosphate (Pi) ion transport into the synaptic terminal. While a transmembrane proton electrical gradient established by a vacuolar-type ATPase powers vesicular glutamate transport, recent studies indicate that binding sites and flux properties for chloride, potassium, and protons within VGLUTs themselves regulate VGLUT activity as well. These intrinsic ionic binding and flux properties of VGLUTs can therefore be modulated by neurophysiological conditions to affect levels of glutamate available for release from synapses. Despite their extraordinary importance, specific and high-affinity pharmacological compounds that interact with these sites and regulate VGLUT function, distinguish between the various modes of transport, and the different isoforms themselves, are lacking. In this review, we provide an overview of the physiologic sites for VGLUT regulation that could modulate glutamate release in an over-active synapse or in a disease state.

An organocatalyzed asymmetric [4+2]-cycloaddition between tropolones and electron-deficient dienophiles is presented. Complex and biologically interesting dihydrohomobarrelenone scaffolds are formed through a Diels-Alder reaction utilizing bifunctional Brønsted-base catalysis, affording the corresponding bridged bicyclic cycloadducts in up to quantitative yields with good enantio- (up to 92 % ee) and diastereoselectivity (up to >20:1 d.r.). The synthetic value of the obtained products is explored by downstream transformations, including photoisomerizations, and their biological relevancy by in vivo testing in MCF-7 cancer cells., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The [8+2] cycloaddition of indene-2-carbaldehydes and nitro olefins is described to provide benzonorbornene scaffolds in a highly peri-, diastereo-, and enantioselective fashion in the presence of a C 2 -symmetric aminocatalyst. This reaction, which proceeds through a transient semi-aromatic amino isobenzofulvene, represents the first example of catalytic formation and transformation of these species. Quantum chemical calculations suggest a kinetically controlled stepwise mechanism where the stereochemistry is determined in the first bond-forming event. Beyond the useful [8+2] cycloadducts, [10+4] cycloadducts have been identified in silico as potential off-pathway intermediates., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Glutamine (Gln) is considered the preferred precursor for the neurotransmitter pool of glutamate (Glu), the major excitatory transmitter in the mammalian CNS. Here, an activity-regulated, high-affinity Gln transport system is described in developing and mature neuron-enriched hippocampal cultures that is potently inhibited by riluzole (IC 50 1.3 ± 0.5 μM), an anti-glutamatergic drug, and is blocked by low concentrations of 2-(methylamino)isobutyrate (MeAIB), a system A transport inhibitor. K + -stimulated MeAIB transport displays an affinity (K m ) for MeAIB of 37 ± 1.2 μM, saturates at ~ 200 μM, is dependent on extracellular Ca 2+ , and is blocked by inhibition of voltage-gated Ca 2+ channels. Spontaneous MeAIB transport is also dependent on extracellullar Ca 2+ and voltage-gated calcium channels, but is also blocked by the Na + channel blocker tetrodotoxin, by Glu receptor antagonists, and by GABA indicating its dependence on intact neural circuits driven by endogenous glutamatergic activity. The transport of MeAIB itself does not rely on Ca 2+ , but on Na + ions, and is pH sensitive. Activity-regulated, riluzole-sensitive spontaneous and K + -stimulated transport is minimal at 7-8 days in vitro, coordinately induced during the next 2 weeks and is maximally expressed by days in vitro > 20; the known period for maturation of the Glu/Gln cycle and regulated pre-synaptic Glu release. Competition analyses with various amino acids indicate that Gln is the most likely physiological substrate. Activity-regulated Gln/MeAIB transport is not observed in astrocytes. The functional identification of activity-regulated, high-affinity, riluzole-sensitive Gln/MeAIB transport in hippocampal neurons may have important ramifications in the neurobiology of activity-stimulated pre-synaptic Glu release, the Glu/Gln cycle between astrocytes and neurons, and neuronal Glu-induced excitotoxicity. Cover Image for this issue: doi: 10.1111/jnc.13805., (© 2017 International Society for Neurochemistry.)

A new indium(III)-catalyzed reaction for the synthesis of a series of indolizine scaffolds has been developed. This methodology was highly efficient, allowing a low catalyst loading of 2 mol % (down to 0.5 mol %) and rendering the products in high yields through a 5-exo-dig aza-Conia-ene reaction. Furthermore, the possibility of incorporating an electrophile into the generated pyrrolidone ring in a one-pot synergistic fashion was demonstrated. Finally, based on experimental observations, a mechanism proposal was outlined., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The facile heterodehydrocoupling of a range of primary or secondary amines and even ammonia with pinacolborane (HBPin) was accomplished using {Ar Me 6 Sn(μ-OMe)} 2 (1, Ar Me 6 = C 6 H 3 -2,6-(C 6 H 2 -2,4,6-Me 3 ) 2 ) as pre-catalysts for a catalytically active tin(ii) hydride. The more sterically hindered pre-catalyst 2, {Ar iPr 4 Sn(μ-OMe)} 2 (Ar iPr 4 = C 6 H 3 -2,6-(C 6 H 3 -2,6-iPr 2 ) 2 ) facilitated the dehydrocoupling only of primary amines with HBPin, and at an increased rate relative to the less crowded {Ar Me 6 Sn(μ-OMe)} 2 . Also presented is {Ar Me 6 Sn(μ-NEt 2 )} 2 (3), which can be converted into the structurally characterizable {Ar Me 6 Sn(μ-NEt 2 )(μ-H)SnAr Me 6 } (4) via the addition of pinacol borane. This, alongside stoichiometric studies, give insight into the mechanism of the catalysis.

We sequenced and annotated the complete 7,170,504-bp genome of a novel secondary metabolite-producingStreptomycesstrain,Streptomyces albusSM254, isolated from copper-rich subsurface fluids at ~220-m depth within the Soudan Iron Mine (Soudan, MN, USA)., (Copyright © 2016 Badalamenti et al.)

We present the first successful isolation and crystallographic characterization of a Mackay 55-metal-atom two-shell icosahedron, Pd55L12(μ3-CO)20 (L = PPr(i)3) (1). Its two-shell icosahedron of pseudo-Ih symmetry (without isopropyl substituents) enables a structural/bonding comparison with interior 55-metal-atom two-shell icosahedral geometries observed within the multi-shell capped 145-metal-atom three-shell Pd145(CO)72(PEt3)30 and 165-metal-atom four-shell Pt-centered (μ12-Pt)Pd164-xPtx(CO)72(PPh3)20 (x ≈ 7) nanoclusters, and within the recently reported four-shell Au133(SC6H4-p-Bu(t))52 nanocluster. DFT calculations carried out on a Pd55(CO)20(PH3)12 model analogue, with triisopropyl phosphine substituents replaced by H atoms, revealed a positive +0.84 e charge for the entire Pd55 core, with a highly positive second-shell Pd42 surface of +1.93 e.

The reaction of the tetrylenes Ge(Ar((Me)6))2, Sn(Ar((Me)6))2, and Pb(Ar((Me)6))2 [Ar((Me)6) = C6H3-2,6-(C6H2-2,4,6-(CH3)3)2] with the group 13 metal alkyls trimethylaluminum and trimethylgallium afforded (Ar((Me)6))2Ge(Me)AlMe2 (1), (Ar((Me)6))2Ge(Me)GaMe2 (2), and (Ar(Me6))2Sn(Me)GaMe2 (3) in good yields via insertion reaction routes. In contrast, the reaction of AlMe3 with Sn(Ar((Me)6))2 afforded the [1.1.1]propellane analogue Sn2{Sn(Me)Ar((Me)6)}3 (5) in low yield, and the reaction of AlMe3 or GaMe3 with Pb(Ar((Me)6))2 resulted in the formation of the diplumbene {Pb(Me)Ar((Me)6)}2 (6) and AlAr((Me)6)Me2 (7) or GaAr((Me)6)Me2 (8) via metathesis. The reaction of Sn(Ar((Me)6))2 with gallium trialkyls was found to be reversible under ambient conditions and analyzed through the reaction of Sn(Ar((Me)6))2 with GaEt3 to form (Ar((Me)6))2Sn(Et)GaEt2 (4), which displayed a dissociation constant Kdiss and ΔGdiss of 8.09(6) × 10(-3) and 11.8(9) kJ mol(-1) at 296 °C. The new compounds were characterized by X-ray crystallography, NMR ((1)H, (13)C, (119)Sn, and (207)Pb), IR, and UV-vis spectroscopies.

Rett syndrome (RTT) is an autism spectrum disorder caused by loss-of-function mutations in the gene encoding MeCP2, an epigenetic modulator that binds the methyl CpG dinucleotide in target genes to regulate transcription. Previously, we and others reported a role of microglia in the pathophysiology of RTT. To understand the mechanism of microglia dysfunction in RTT, we identified a MeCP2 target gene, SLC38A1, which encodes a major glutamine transporter (SNAT1), and characterized its role in microglia. We found that MeCP2 acts as a microglia-specific transcriptional repressor of SNAT1. Because glutamine is mainly metabolized in the mitochondria, where it is used as an energy substrate and a precursor for glutamate production, we hypothesize that SNAT1 overexpression in MeCP2-deficient microglia would impair the glutamine homeostasis, resulting in mitochondrial dysfunction as well as microglial neurotoxicity because of glutamate overproduction. Supporting this hypothesis, we found that MeCP2 downregulation or SNAT1 overexpression in microglia resulted in (1) glutamine-dependent decrease in microglial viability, which was corroborated by reduced microglia counts in the brains of MECP2 knock-out mice; (2) proliferation of mitochondria and enhanced mitochondrial production of reactive oxygen species; (3) increased oxygen consumption but decreased ATP production (an energy-wasting state); and (4) overproduction of glutamate that caused NMDA receptor-dependent neurotoxicity. The abnormalities could be rectified by mitochondria-targeted expression of catalase and a mitochondria-targeted peptide antioxidant, Szeto-Schiller 31. Our results reveal a novel mechanism via which MeCP2 regulates bioenergetic pathways in microglia and suggest a therapeutic potential of mitochondria-targeted antioxidants for RTT., (Copyright © 2015 the authors 0270-6474/15/352516-14$15.00/0.)

As societal demand for food, water and other life-sustaining resources grows, the science of ecosystem services (ES) is seen as a promising tool to improve our understanding, and ultimately the management, of increasingly uncertain supplies of critical goods provided or supported by natural ecosystems. This promise, however, is tempered by a relatively primitive understanding of the complex systems supporting ES, which as a result are often quantified as static resources rather than as the dynamic expression of human-natural systems. This article attempts to pinpoint the minimum level of detail that ES science needs to achieve in order to usefully inform the debate on environmental securities, and discusses both the state of the art and recent methodological developments in ES in this light. We briefly review the field of ES accounting methods and list some desiderata that we deem necessary, reachable and relevant to address environmental securities through an improved science of ES. We then discuss a methodological innovation that, while only addressing these needs partially, can improve our understanding of ES dynamics in data-scarce situations. The methodology is illustrated and discussed through an application related to water security in the semi-arid landscape of the Great Ruaha river of Tanzania.