A molecular mechanism for the effect of lithium on development.

Lithium, one of the most effective drugs for the treatment of bipolar (manic-depressive) disorder, also has dramatic effects on morphogenesis in the early development of numerous organisms. How lithium exerts these diverse effects is unclear, but the favored hypothesis is that lithium acts through inhibition of inositol monophosphatase (IMPase). We show here that complete inhibition of IMPase has no effect on the morphogenesis of Xenopus embryos and present a different hypothesis to explain the broad action of lithium. Our results suggest that lithium acts through inhibition of glycogen synthase kinase-3 beta (GSK-3 beta), which regulates cell fate determination in diverse organisms including Dictyostelium, Drosophila, and Xenopus. Lithium potently inhibits GSK-3 beta activity (Ki = 2 mM), but is not a general inhibitor of other protein kinases. In support of this hypothesis, lithium treatment phenocopies loss of GSK-3 beta function in Xenopus and Dictyostelium. These observations help explain the effect of lithium on cell-fate determination and could provide insights into the pathogenesis and treatment of bipolar disorder.

Crystallographic evidence for the action of potassium, thallium, and lithium ions on fructose-1,6-bisphosphatase.

Fructose-1,6-bisphosphatase (Fru-1,6-Pase; D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11) requires two divalent metal ions to hydrolyze alpha-D-fructose 1,6-bisphosphate. Although not required for catalysis, monovalent cations modify the enzyme activity; K+ and Tl+ ions are activators, whereas Li+ ions are inhibitors. Their mechanisms of action are still unknown. We report here crystallographic structures of pig kidney Fru-1,6-Pase complexed with K+, Tl+, or both Tl+ and Li+. In the T form Fru-1,6-Pase complexed with the substrate analogue 2,5-anhydro-D-glucitol 1,6-bisphosphate (AhG-1,6-P2) and Tl+ or K+ ions, three Tl+ or K+ binding sites are found. Site 1 is defined by Glu-97, Asp-118, Asp-121, Glu-280, and a 1-phosphate oxygen of AhG-1,6-P2; site 2 is defined by Glu-97, Glu-98, Asp-118, and Leu-120. Finally, site 3 is defined by Arg-276, Glu-280, and the 1-phosphate group of AhG-1,6-P2. The Tl+ or K+ ions at sites 1 and 2 are very close to the positions previously identified for the divalent metal ions. Site 3 is specific to K+ or Tl+. In the divalent metal ion complexes, site 3 is occupied by the guanidinium group of Arg-276. These observations suggest that Tl+ or K+ ions can substitute for Arg-276 in the active site and polarize the 1-phosphate group, thus facilitating nucleophilic attack on the phosphorus center. In the T form complexed with both Tl+ and Li+ ions, Li+ replaces Tl+ at metal site 1. Inhibition by lithium very likely occurs as it binds to this site, thus retarding turnover or phosphate release. The present study provides a structural basis for a similar mechanism of inhibition for inositol monophosphatase, one of the potential targets of lithium ions in the treatment of manic depression.

On the well-posedness of a mathematical model for lithium-ion batteries.

We discuss the well-posedness of a mathematical model that is used in the literature for the simulation of lithium-ion batteries. First, a mathematical model based on a macrohomogeneous approach is presented, following previous work. Then it is shown, from a physical and a mathematical point of view, that a boundary condition widely used in the literature is not correct. Although the errors could be just sign typos (which can be explained as carelessness in the use of d/dx versus d/dn, with n the outward unit vector) and authors using this model probably use the correct boundary condition when they solve it in order to do simulations, readers should be aware of the right choice. Therefore, the deduction of the correct boundary condition is done here, and a mathematical study of the well-posedness of the corresponding problem is presented.

Hα emission fluxes and lithium abundances of low-mass stars in the young open cluster IC 4665

As part of a long term effort to understand pre-main sequence Li burning, we have obtained high resolution spectroscopic observations of 14 late type stars (G0-M1) in the young open cluster IC 4665. Most of the stars have Hα filled-in and Li I absorption, as expected for their young age. From the equivalent widths of Hα emission excess (obtained using the spectral subtraction technique) and the the Li i λ6708 feature, we have derived Hα emission fluxes and photospheric Li abundances. The mean Li abundance of IC 4665 solar-type stars is log N(Li) = 3.1; the same as in other young clusters (α Per, Pleiades) and T Tauri stars. Our results support the conclusions from previous works that PMS Li depletion is very small for masses ∼ 1 M_⨀ . Among the IC 4665 late-G and early K-type stars, there is a spread in Li abundances of about one order of magnitude. The Li-poor IC 4665 members have low Hα excess and vsini≤10. Hence, the Li-activity-rotation connection which has been clearly established in the Pleiades also seems to hold in IC 4665. One M-type IC 4665 star that we have observed does not show Li, implying a very efficient Li depletion as observed in α Per stars of the same spectral type. The level of chromospheric activity and Li depletion among the low-mass stars of IC 4665 is similar to that in the Pleiades. In fact, we note that the Li abundance distributions in several young clusters (α Per, Pleiades, IC 2391, IC 4665) and in post T Tauri stars are strikingly similar. This result suggests that Hα emission and Li abundance not well correlated with age for low-mass stars between 20 and 100 Myr old. We argue that a finer age indicator, the ''LL-clock'', would be the luminosity at which the transition between efficient Li depletion and preservation takes place for fully convective objects. The LL-clock could allow in the near future to derive the relative ages of young open clusters, and clarify the study of PMS evolution of cool stars.

A Comparison of the Impacts of Lithium Extraction and Lithium Recycling Processes

Lithium is used in the cathode and electrolyte of rechargeable batteries in many portable electronics and electric vehicles, and is thus seen as a critical component of modern technology (Gruber et al., 2011). Electric vehicles are promoted as a way to reduce carbon emissions associated with the transportation sector, which accounts for 14.3% of anthropogenic greenhouse gas emissions (OECD International Transport Forum, 2010). However, the sustainability of lithium procurement will influence the overall environmental impact of this proposed “green” solution. It is estimated that 66% of the world’s lithium resource is contained in natural brines, 24% in pegmatites, and 8% in sedimentary rocks such as hectorite clays (Gruber et al., 2011). It has been shown that “[r]ecycling of lithium from Li-ion batteries may be a critical factor in balancing the supply of lithium with future demand” (Gruber et al., 2011). In an attempt to quantify energy and materials consumption associated with production of a unit of useful lithium compounds, industry reports and peer-reviewed scientific literature concerning lithium mining and lithium recycling were reviewed and compared. Other aspects of sustainability, such as waste or by-products produced in the production of a unit of useful lithium, were also explored. Thus, this paper will serve to further the evaluation of the comparative environmental consequences associated with lithium production via extraction versus recycling. Efficiencies must be made in both processes to maximize productivity while minimizing ecological harm.

Lithium isotopic composition of pore fluids and sediments in the Costa Rica subduction zone

Pore fluid and sediment Li concentrations and isotopic ratios provide important insights on the hydrology, sediment contribution to the arc volcanoes and fluid-sediment reactions at the dominantly non-accretionary Costa Rica subduction zone. Ocean Drilling Program Site 1039 in the trench axis provides a reference section of 400 m of the incoming sediments, and Site 1040, situated arcward from the trench, consists of a deformed sedimentary wedge and apron sediments, the décollement, and the partially dewatered underthrust sediment section. At the reference site, pore fluids show important isotopic variations (delta6Li=-21.7 to -37.8 per mil), reflecting the interplay of in situ alteration of volcanic material and ion exchange with clay minerals. In the basal section, a reversal of Li concentration and delta6Li toward seawater values is observed, providing supporting evidence for a lateral seawater flow system in the upper oceanic basement underlying this sediment section. At Site 1040, pore fluid of the lower deformed wedge sediments and within the décollement is enriched in Li and the isotopic compositions are relatively light, suggesting infiltration of a deep-seated fluid. The delta6Li value of -22 per mil of this Li-enriched fluid (261 µM), when compared with the delta6Li value of the subducted sediment section (-11 per mil), suggests that the deep source fluid originates from mineral fluid dehydration and transformation reactions at temperatures of 100 to 150°C, consistent with the temperature range of the up-dip seismogenic zone and of transformation of smectite to illite. The distribution of Li and its isotopes in the underthrust section are similar to those at the reference site, indicating near complete subduction of the incoming sediments and that early dewatering of the underthrust sediments occurs predominantly by lateral flow into the ocean. The hemipelagic clay-rich sediment section of the subducting plate carries most of the Li into this subduction zone, and the pelagic diatomaceous and nannofossil calcareous oozes contain little Li. The Li isotopes of both the clay-rich hemipelagic sediments and of the pelagic oozes are, however, similar, with delta6Li values of -9 to -12 per mil. The observations that (1) the delta6Li values of the underthrust sediments are distinctly lower than that of the mantle, and (2) the lavas of the Costa Rican volcanoes are enriched in Li and 7Li, provide an approximation of the contribution of the subducted sediments to the arc volcanoes. A first order mass balance calculation suggests that approximately half of the Li flux delivered by subducted sediments and altered oceanic crust into the Middle American Trench is recycled to the Costa Rican arc and at most a quarter of sedimentary Li is returned into the ocean through thrust faults, primarily the décollement thrust.

(Table 1) Lithium contents and isotopic composition in sediments from DSDP Holes 64-477 and 64-477A

Lithium isotopic compositions of hydrothermally altered sediments of Deep Sea Drilling Project (DSDP) site 477/477A, as well as high temperature vent fluids of the Guaymas Basin, have been determined to gain an understanding of lithium exchange during fluid-sediment interaction at this sediment-covered spreading center. Unaltered turbidite of the basin has a d6Li value of -10%, 5-7% heavier than fresh oceanic basalts. Contact metamorphism induced by a shallow sill intrusion results in a decrease of the lithium content of the adjacent sediments and a lighter isotopic value (-8%). Below the sill, sediments altered by a deep-seated hydrothermal system show strong depletions in lithium, while lithium isotopic compositions vary greatly, ranging from -11 to +1%. The shift to lighter composition is the result of preferential retention of the lighter isotope in recrystallized phases after destruction of the primary minerals. The complexity of the isotope profile is attributed to inhomogeneity in mineral composition, the tortuous pathway of fluids and the temperature effect on isotopic fractionation. The range of lithium concentration and d6Li values for the vent fluids sampled in 1982 and 1985 overlaps with that of the sediment-free mid-ocean ridge systems. The lack of a distinct expression of sediment input is explained in terms of a flow-through system with continuous water recharge. The observations on the natural system agree well with the results of laboratory hydrothermal experiments. The experimental study demonstrates the importance of temperature, pressure, water/rock ratio, substrate composition and reaction time on the lithium isotopic composition of the reacted fluid. High temperature authigenic phases do not seem to constitute an important sink for lithium and sediments of a hydrothermal system such as Guaymas are a source of lithium to the ocean. The ready mobility of lithium in the sediment under elevated temperature and pressure conditions also has important implications for lithium cycling in subduction zones.

Lithium and rubidium concentrations in waters of seas and oceans

Data on lithium, rubidium and cesium concentrations in waters of open seas and oceans are summarized. Average amounts of these elements in the World Ocean inferred from published data and those obtained by the author are as follows: Li - 0.18 mg/l, Rb - 0.12 mg/l and Cs - 0.004 mg/l. Rare alkaline elements in the oceans and open seas are distributed (like sodium and potassium) in accordance with salinity. The ability of lithium to become a constituent of clay minerals accounts for its relatively low concentration in sea water as compared with that of sodium and potassium. Compared to rubidium and cesium that have high absorption energy and low hydration energy, lithium relatively enriches sea water. Residence times of these elements in the ocean are: Na - 120 My, Li - 2.7 My, Rb - 2.3 My and Cs - 0.3 My.

Lithium and lithium hydride : chemical and physical properties : a literature search /

This literature search consisting of 187 references to report and published literature taken from Nuclear Science Abstracts (NSA). The period covered is January, 1951 - November 15, 1960. Abstracts for the references can be found in NSA by the abstract numbers provided.

The use of lithium to prevent or mitigate alkali-silica reaction in concrete pavements and structures /

"March 2007."

The electrical resistivity of lithium and sodium-potassium alloy /

"Contract AT(11-1)-229."

The solubility of helium in lithium and potassium /

"Contract AT(30-1)-2789."

Thermocouple development lithium-cooled reactor experiment /

"Contract AT(30-1)-2789."

Deuterided lithium wire /

"U.S. Atomic Energy Commission Contract AT(29-1)-1106."

Electrochemical investigation of liquid amalgams of thallium, indium, tin, zinc, cadmium, lead, copper, and lithium.

"Contributions from the Chemical Laboratory of Harvard College."