Do measures of social support and social distress share general factors associated with suicidal ideation and attempts?

INTRODUCTION: Aspects of social relationships have variably been associated with suicidal ideation (SI) and suicide attempts (SAs). This study assessed whether social support and social distress measures have general factors versus measure-specific factors that are associated with suicide risk. METHODS: Adults (N = 455, 60.0% female), admitted to psychiatric inpatient units following a recent suicide attempt or active SI, completed assessments of social support (emotional support, instrumental support, friendship, perceived support from significant others, friends, family) and social distress (loneliness, perceived rejection, perceived burdensomeness, thwarted belongingness). Bifactor modeling examined general and specific factors of social support and distress in relation to SI (week prior to hospitalization, via the Beck Scale for SI) and SAs (past 30 days, via the Columbia Suicide Severity Rating Scale). RESULTS: SI was significantly associated with the general social support (B = -1.51), the general social distress (B = 1.67), and the specific perceived burdensomeness (B = 1.57) factors. SAs were significantly associated with the specific Perceived Rejection (OR = 1.05) and Thwarted Belongingness (OR = 0.91) factors. CONCLUSION: General social support and social distress were associated with SI but not recent SAs. Specific social distress factors were also related to SI and SAs controlling for general social distress, suggesting areas for future interventions.

Unifying the Hydrogen Evolution and Oxidation Reactions Kinetics in Base by Identifying the Catalytic Roles of Hydroxyl-Water-Cation Adducts.

Despite the fundamental and practical significance of the hydrogen evolution and oxidation reactions (HER/HOR), their kinetics in base remain unclear. Herein, we show that the alkaline HER/HOR kinetics can be unified by the catalytic roles of the adsorbed hydroxyl (OHad)-water-alkali metal cation (AM+) adducts, on the basis of the observations that enriching the OHad abundance via surface Ni benefits the HER/HOR; increasing the AM+ concentration only promotes the HER, while varying the identity of AM+ affects both HER/HOR. The presence of OHad-(H2O) x-AM+ in the double-layer region facilitates the OHad removal into the bulk, forming OH--(H2O) x-AM+ as per the hard-soft acid-base theory, thereby selectively promoting the HER. It can be detrimental to the HOR as per the bifunctional mechanism, as the AM+ destabilizes the OHad, which is further supported by the CO oxidation results. This new notion may be important for alkaline electrochemistry.

Resolving the Iron Phthalocyanine Redox Transitions for ORR Catalysis in Aqueous Media.

Metal macrocycles are among the most important catalytic systems in electrocatalysis and biocatalysis owing to their rich redox chemistry. Precise understanding of the redox behavior of metal macrocycles in operando is essential for fundamental studies and practical applications of this catalytic system. Here we present electrochemical data for the representative iron phthalocyanine (FePc) in both aqueous and nonaqueous media coupled with in situ Raman and X-ray absorption analyses to challenge the traditional notion of the redox transition of FePc at the low potential end in aqueous media by showing that it arises from the redox transition of the ring. Our data unequivocally demonstrate that the electron is shuttled to the Pc ring via the Fe(II)/Fe(I) redox center. The Fe(II)/Fe(I) redox transition of FePc in aqueous media is indiscernible by normal spectroscopic methods owing to the lack of a suitable axial ligand to stabilize the Fe(I) state.

Comment on "Cycling Li-O2 batteries via LiOH formation and decomposition".

Based on a simple thermodynamic analysis, we show that iodide-mediated electrochemical decomposition of lithium hydroxide (LiOH) likely occurs through a different mechanism than that proposed by Liu et al (Research Article, 30 October 2015, p. 530). The mismatch in thermodynamic potentials for iodide/triiodide (I(-)/I3 (-)) redox and O2 evolution from LiOH implies a different active iodine/oxygen electrochemistry on battery charge. It is therefore possible that the system described in Liu et al may not form the basis for a rechargeable lithium-oxygen (Li-O2) battery.

A Search for the Optimum Lithium Rich Layered Metal Oxide Cathode Material for Li-Ion Batteries.

We report the results of a comprehensive study of the relationship between electrochemical performance in Li cells and chemical composition of a series of Li rich layered metal oxides of the general formula xLi2MnO3 · (1-x)LiMn0.33Ni0.33Co0.33O2 in which x = 0,1, 0.2, 0,3, 0.5 or 0.7, synthesized using the same method. In order to identify the cathode material having the optimum Li cell performance we first varied the ratio between Li2MnO3 and LiMO2 segments of the composite oxides while maintaining the same metal ratio residing within their LiMO2 portions. The materials with the overall composition 0.5Li2MnO3 · 0.5LiMO2 containing 0.5 mole of Li2MnO3 per mole of the composite metal oxide were found to be the optimum in terms of electrochemical performance. The electrochemical properties of these materials were further tuned by changing the relative amounts of Mn, Ni and Co in the LiMO2 segment to produce xLi2MnO3 · (1-x)LiMn0.50Ni0.35Co0.15O2 with enhanced capacities and rate capabilities. The rate capability of the lithium rich compound in which x = 0.3 was further increased by preparing electrodes with about 2 weight-percent multiwall carbon nanotube in the electrode. Lithium cells prepared with such electrodes were cycled at the 4C rate with little fade in capacity for over one hundred cycles.

Prospects and Limits of Energy Storage in Batteries.

Energy densities of Li ion batteries, limited by the capacities of cathode materials, must increase by a factor of 2 or more to give all-electric automobiles a 300 mile driving range on a single charge. Battery chemical couples with very low equivalent weights have to be sought to produce such batteries. Advanced Li ion batteries may not be able to meet this challenge in the near term. The state-of-the-art of Li ion batteries is discussed, and the challenges of developing ultrahigh energy density rechargeable batteries are identified. Examples of ultrahigh energy density battery chemical couples include Li/O2, Li/S, Li/metal halide, and Li/metal oxide systems. Future efforts are also expected to involve all-solid-state batteries with performance similar to their liquid electrolyte counterparts, biodegradable batteries to address environmental challenges, and low-cost long cycle-life batteries for large-scale energy storage. Ultimately, energy densities of electrochemical energy storage systems are limited by chemistry constraints.

Lck domains differentially contribute to pre-T cell receptor (TCR)- and TCR-alpha/beta-regulated developmental transitions.

Maturational changes at the CD4(-)CD8(-) double negative (DN) to CD4(+)CD8(+) double positive (DP) transition are dependent on signals generated via the pre-T cell receptor (TCR) and the nonreceptor protein tyrosine kinase p56(lck) (Lck). How Lck activities are stimulated or relayed after pre-TCR formation remains obscure. Our structure-function mapping of Lck thymopoietic properties reveals that the noncatalytic domains of Lck are specialized to signal efficient cellular expansion at DN to DP transition. Moreover, although substitution of the Lck catalytic domain with FynT sequences minimally impacts DP development, single positive thymocytes are most efficiently produced in the presence of kinases containing both the NH(2)-terminal and catalytic regions of Lck. These findings demonstrate that the Lck structure is uniquely adapted to mediate signals at both major transitions in thymopoiesis.

Regulation of Src-family protein tyrosine kinase transcription during lymphocyte ontogeny.

The distribution and quantity of cellular signaling elements influence response patterns to a variety of stimuli. As protein tyrosine phosphorylation is a requisite event induced by a majority of surface receptors, and protein tyrosine kinases of the src-family (src-PTKs) act as proximal transducers for many hematopoietic receptors, we have designed a quantitative RT-PCR assay to measure src-family PTK expression during critical stages of lymphocyte ontogeny. With this assay we demonstrate that the distal promoter element regulating expression of lck, a src-PTK essential for T-cell development and activation, is similarly regulated during ontogeny of T and B cells. However, lck transcript abundance is drastically reduced in B lineage cells, suggesting that transcriptional elements influencing lck promoter activity are modulated in these cells. Moreover, although transcripts encoding the src-PTK fyn accumulate at 0.1% of lck mRNA levels in thymocytes, diminished activity of the lck distal promoter in the B-cell background brings lck and fyn transcript levels to near equivalence in this population. Importantly, transcripts arising from the lck distal promoter element and the fyn locus are similarly upregulated during developmental transitions associated with antigen-receptor expression in both B and T cells. These findings suggest that although the magnitude of lck and fyn expression is differentially regulated in B and T cells, expression at these loci is similarly developmentally programmed during ontogeny of both lymphocyte lineages.

Targets of p56(lck) activity in immature thymoblasts: stimulation of the Ras/Raf/MAPK pathway.

Previous studies suggest that p56(lck) activity influences thymocyte development at a stage prior to TCR alphabeta expression. Transgenic mice that express high levels of p56(lck) activity during thymopoiesis develop thymic lymphomas consisting of cells with immature surface phenotypes. We have utilized cell lines derived from lck-induced thymic tumors to define biochemical pathways regulated by p56(lck) activity in immature thymocytes. Here we report that components of the Ras/Raf/MAPK pathway are constitutively activated in these lck-transformed immature thymoblasts. p56(lck) utilizes Shc and Grb2 adaptors to mediate activation of p21(ras) in the thymoblast lines by promoting tyrosine phosphorylation of the Shc protein and constitutive interaction between Shc and Grb2. The putative guanine nucleotide exchange factor p95(vav) is also maintained in constitutively tyrosine phosphorylated form as a result of elevated Lck activity. One target of activated Ras, the Raf-1 kinase, is hyperphosphorylated and downstream targets of activated Raf-1, Erk1 and Erk2, are hyperphosphorylated and activated in Lck-transformed thymocytes. Forskolin treatment reverses Raf-1 hyperphosphorylation in the cells and inhibits proliferation by blocking G1/S transition. In contrast, conventional protein tyrosine kinase inhibitors block proliferation by arresting Lck thymoblasts at G2/M. Lck-mediated stimulation of the Ras/Raf/MAPK pathway is also required to maintain cell viability by preventing programmed cell death. In summary, p56(lck) activity stimulates G1/S transition in immature thymoblasts and maintains cell viability via transduction of constitutive activation signals downstream to components of the Ras/Raf/MAPK pathway.

Decreased signaling competence as a result of receptor overexpression: overexpression of CD4 reduces its ability to activate p56lck tyrosine kinase and to regulate T-cell antigen receptor expression in immature CD4+CD8+ thymocytes.

Thymic selection of the developing T-cell repertoire occurs in immature CD4+CD8+ thymocytes, with the fate of individual thymocytes determined by the specificity of T-cell antigen receptor they express. However, T-cell antigen receptor expression in immature CD4+CD8+ thymocytes is actively down-regulated in CD4+CD8+ thymocytes by CD4-mediated tyrosine kinase signals that are generated in the thymus as a result of CD4 engagement by intrathymic ligands. In the present study we have examined the effect of CD4 overexpression in CD4+CD8+ thymocytes on activation of CD4-associated p56lck tyrosine kinase and regulation of T-cell antigen receptor expression. Augmented CD4 expression in CD4+CD8+ thymocytes did not result in commensurate increases in associated p56lck molecules, so that CD4 expression was quantitatively disproportionate to that of its associated signaling molecule p56lck. Interestingly, we found that CD4 overexpression significantly interfered with the ability of CD4 crosslinking to activate associated p56lck molecules and significantly interfered with the ability of CD4 to regulate T-cell antigen receptor expression. Thus, this study provides an example in which receptor overexpression leads to decreased receptor signaling competence.

The protein tyrosine kinase p56lck regulates thymocyte development independently of its interaction with CD4 and CD8 coreceptors [corrected].

The lck gene encodes a lymphocyte-specific protein tyrosine kinase of the nonreceptor type that is implicated in signal transduction pathways emanating from the CD4 and CD8 coreceptors. Previous studies also support a role for p56lck in regulating T cell receptor beta gene rearrangements and, more generally, thymocyte development. Here we report that a mutant form of p56lck, which is incapable of interacting with CD4 or CD8, behaves indistinguishably from association-competent p56lck with respect to its ability to affect thymocyte maturation. The effects of p56lck remained specific in that the closely related src-family kinase p59hck was incapable of substituting for p56lck in arresting beta locus gene rearrangements. These data support the view that src-family kinases perform highly specialized and often nonoverlapping functions in hematopoietic cells, and that p56lck acts independently of its association with CD4 and CD8 to regulate thymocyte development.

Inhibition of T-cell receptor beta-chain gene rearrangement by overexpression of the non-receptor protein tyrosine kinase p56lck.

The variable region genes of the T cell receptor (TCR) alpha and beta chains are assembled by somatic recombination of separate germline elements. During thymocyte development, gene rearrangements display both an ordered progression, with beta chain formation preceding alpha chain, and allelic exclusion, with each cell containing a single functional beta chain rearrangement. Although considerable evidence supports the view that the individual loci are regulated independently, signaling molecules that may participate in controlling TCR gene recombination remain unidentified. Here we report that the lymphocyte-specific protein tyrosine kinase p56lck, when overexpressed in developing thymocytes, provokes a reduction in V beta--D beta rearrangement while permitting normal juxtaposition of other TCR gene segments. Our data support a model in which p56lck activity impinges upon a signaling process that ordinarily permits allelic exclusion at the beta-chain locus.

Delayed thymocyte development induced by augmented expression of p56lck.

Accumulating evidence supports the contention that CD4 and CD8 receptor molecules play a critical signaling role during thymocyte development. The lymphocyte-specific protein tyrosine kinase (p56lck), by virtue of its physical association with these surface components, provides a likely candidate for the biochemical signal transducing element required for these effects. To investigate the function of p56lck in T lymphocytes, transgenic mice were produced that carry either the wild-type lck gene or a mutated lck gene encoding a constitutively activated form of p56lck (p56lckF505). Both transgenes were expressed in thymocytes under the control of the lck proximal promoter element. A large set of founder animals was obtained in which steady-state accumulation of lck transgene mRNA directly correlated with transgene copy number, suggesting that this transgene contains a dominant control region. Progeny of these founders exhibited a transgene-dependent dose-related decrease in the production of thymocytes bearing functional antigen receptors. This effect was strictly dependent on p56lck activity, in that both wild-type and mutated versions of the genes induced similar effects with differing efficiencies. Remarkably, even a twofold increase in p56lck abundance was sufficient to substantially disrupt the appearance of functional thymocytes. These results indicate that thymocyte maturation is regulated in part by signals derived from p56lck.

Thymic tumorigenesis induced by overexpression of p56lck.

The lck gene encodes a membrane-associated protein tyrosine kinase (p56lck) that is believed to participate in lymphocyte-specific signal transduction pathways. To investigate the function of this molecule, transgenic mice were generated carrying the wild-type lck gene or a mutated lck gene encoding a constitutively activated form of p56lck (p56lckF505). Transgene expression in thymocytes was achieved in each case using the lck proximal promoter element. Mice expressing high levels of either p56lckF505 or p56lckY505 reproducibly developed thymic tumors. The sensitivity of thymocytes to p56lck-induced transformation suggests that disturbances in lck expression may contribute to the pathogenesis of some human neoplastic diseases.

Regulation of T cell receptor signaling by a src family protein-tyrosine kinase (p59fyn).

Engagement of the clonotypic antigen receptor (TCR) on T lymphocytes provokes an activation response leading to cell proliferation and lymphokine secretion. To examine the molecular basis of T cell signaling, we generated transgenic animals in which a lymphocyte-specific nonreceptor protein-tyrosine kinase p59fyn(T) is 20-fold overexpressed in developing T lineage cells. Thymocytes from these mice, analyzed using both cellular and biochemical assays, were remarkably hyperstimulable. Moreover, the responsiveness of normal thymocytes to TCR-derived signals correlated well with the extent to which p59fyn was expressed in these cells. Overexpression of a catalytically inactive form of p59fyn substantially inhibited TCR-mediated activation in otherwise normal thymocytes. These effects are unique to p59fyn; overexpression of a closely related T cell-specific tyrosine kinase, p56lck, elicits dramatically different phenotypes. Our results suggest that p59fyn is a critically important component of the TCR signal transduction apparatus.

Developmental regulation of lck gene expression in T lymphocytes.

In the mouse and human, mRNA transcripts encoding the lymphocyte-specific protein tyrosine kinase p56lck are derived from two separate promoters resulting in heterogeneity in the 5' untranslated region sequence. The proximal promoter lies just 5' to the coding region for the gene and is active only in thymocytes. In contrast, the distal promoter lies 34 kilobases (kb) 5' in the human, and is active both in thymocytes and mature peripheral T cells. As previously reported, transgenic mice bearing functional proximal promoter sequence juxtaposed with the SV40 large T antigen gene invariably develop lymphoid tumors confined to the thymus. In the current work, transgenic mice bearing a 2.6-kb fragment of the human distal promoter fused to the SV40 large T antigen gene express large T antigen in thymocytes and in peripheral lymphoid cells, and develop tumors of both the thymus and the peripheral lymphoid organs. The ability of the human distal promoter to function appropriately in transgenic mice is consistent with the strong similarity observed between the mouse and human distal promoter sequences. With the exception of a single short interval that serves as a target for binding of nuclear factors, significant sequence similarity is not seen when the distal and proximal promoter sequences are compared. Hence, developmentally regulated, lineage-specific transcription of the lck gene is mediated by distinct promoter sequences that appear to be capable of functioning independently.

The isotype potential of B cells present in BALB/c mice chronically infected with Mesocestoides corti.

Infection of BALB/c mice with Mesocestoides corti results in a chronic infection with a pronounced splenomegaly and hypergammaglobulinemia. A prominent feature of this infection is that the vast majority of serum immunoglobulin produced is restricted to IgG1 and IgM. As much as 30-fold increases in serum IgG1 levels have been noted. To ascertain whether, as a result of infection, the resident B cell pool is committed to IgG1, B cells from infected animals were tested for their ability to produce various isotypes after stimulation. In one series of experiments, B cells from normal and infected animals were used as donor cells in the splenic fragment assay. The results show that the frequency of 2,4-dinitrophenyl-specific and phosphorylcholine-specific B cells remains unaltered in infected animals compared to controls. Importantly, the hapten-specific B cell clones induced were found to express multiple isotypes. These results demonstrate that the nonactivated B cell pool in spleens of infected mice is not committed to IgG1 and IgM production.

Disruption of thymocyte development and lymphomagenesis induced by SV40 T-antigen.

The lck gene encodes a membrane-associated protein tyrosine kinase that is expressed specifically in lymphoid cells, especially thymocytes. Structural analysis of the murine and human lck genes previously identified conserved 5' flanking sequences that were proposed to represent transcriptional regulatory elements. Here we demonstrate that a murine lck promoter construct containing these sequences directs the expression of the SV40 T-antigen gene in lymphoid cells. Remarkably, expression of SV40 T-antigen in transgenic animals dramatically disturbs thymic development, resulting in preferential loss of CD4+CD8+ thymocytes. In contrast, immature cells lacking both CD4 and CD8 markers are present in near-normal numbers. Thus SV40 T-antigen expression appears partially to arrest thymopoiesis. Mice bearing the lck-SV40 transgene develop readily explantable thymic tumors at 12-18 weeks of age. Fluorocytometric analyses of lck-SV40 tumor cells reveal that immature thymocytes are frequently immortalized. The lck-SV40 mouse may therefore provide materials for the in vitro investigation of thymocyte differentiation.