Prediction of a two-dimensional high Curie temperature Weyl nodal line kagome semimetal.

Kagome lattices may have numerous exotic physical properties, such as stable ferromagnetism and topological states. Herein, combining the particle swarm structure search method with first-principles calculations, we identify a two-dimensional (2D) kagome Mo2Se3 crystal structure with space group P6/mmm. The results show that 2D kagome Mo2Se3 is a 100% spin-polarized topological nodal line semimetal and exhibits excellent ambient stability. The band crossing points form two nodal loops around the high-symmetry points Γ and K. On the other hand, Mo2Se3 shows intrinsic ferromagnetism with a large magnetic moment of 3.05 µB per Mo atom and magnetic anisotropy energy (MAE) of 4.78 meV. Monte Carlo simulations estimate that Mo2Se3 possesses a high Curie temperature of about 673 K. In addition, its ferromagnetic ground state can be well preserved under external strain, and the MAE can be improved by increasing the strain. More importantly, the position of each nodal line can be adjusted to the Fermi level through hole doping. This multifunctional 2D magnetic material that combines spin and topology has great potential in the field of nanoscale spintronic devices.

Longitudinal development of children's sharing behaviour: Only children versus children with siblings from rural China.

This study examined the development of children's sharing behaviour towards friends and strangers using dictator games with a longitudinal design in a sample of rural Chinese children (n = 589, 47.0% girls) at 3-4 years old and 2 years later (n = 453, 44.2% girls). Results showed that the willingness to share and the amount of sharing changed over time and were affected by family structure. Only children shared fewer stickers than non-only children at ages 3-4, but the amount they shared did not differ at ages 5-6. Only children may develop reciprocal friendships at an older age due to their lack of experience with siblings. Children shared more stickers with friends than strangers at ages 3-4, and such ingroup bias became stronger at ages 5-6.

Luteolin alleviates ulcerative colitis through SHP-1/STAT3 pathway.

BACKGROUND: Previous studies have demonstrated that Luteolin has a positive effect on epithelial barrier integrity by promoting the function of tight protein, however, little is known about the underline mechanism of Luteolin. In this study, we constructed Caco-2 cell monolayer to explore the effects and the regulation mechanism of Luteolin in intestinal epithelial barrier integrity. METHODS: Caco-2 cells were co-treated with TNF-α, Interferon-γ (IFN-γ) and Luteolin for 24 h. Overexpression or knockdown of SHP-1 was applied to study the effects of protein phosphoserine phosphatase-1 (SHP-1) on epithelial barrier integrity. Cell viability was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Barrier function was detected by trans-epithelial electrical resistance (TEER) and FITC-dextran assay. The expression levels of SHP-1, phosphorylation signal transducer and activator of transcription 3 (p-STAT3), STAT3 and tight junction proteins were measured by qRT-PCR or western blot. In vivo model of ulcerative colitis was established to detect the function of Luteolin in ulcerative colitis. RESULTS: We clarified that Luteolin protected intestinal epithelial barrier function of Caco-2 monolayers by increasing the resistance values and tight junction (TJ) protein expression. The expression of OCLN, CLDN1, and ZO1 was increased by Luteolin, while the expression of CLDN2 was decreased. Furthermore, Luteolin significantly alleviated the symptom of ulcerative colitis in DSS-induced mice. The in vitro cell model proved that overexpression of SHP-1 promotes the epithelial barrier function and knockdown of SHP-1 or STAT3 activation destroyed the protective effects of Luteolin on the expression of TJ proteins. CONCLUSION: We found that the treatment of Luteolin promoted epithelial barrier function and Luteolin might preserve intestinal epithelial barrier function through suppression of STAT3 signaling pathway by SHP-1.

Actinomadura craniellae sp. nov., isolated from a marine sponge in the South China Sea.

A novel marine actinomycete, designated LHW63021T, was isolated from a marine sponge, genus Craniella, collected in the South China Sea. A polyphasic approach was applied to characterize the taxonomic position of this strain. The strain was found to have scarce aerial mycelia that differentiated into spore chains. The cell-wall hydrolysates contained meso-diaminopimelic acid as the diagnostic diamino acid. Glucose, galactose, mannose and madurose were found in the whole-cell hydrolysates. The dominant polar lipids were phosphatidylinositol and diphosphatidylglycerol. MK-9(H6) and MK-9(H8) were the predominant menaquinones. The major fatty acids were iso-C16 : 0, iso-C18 : 0, 10-methyl C17 : 0 and C18 : 1 ω9c. The DNA G+C content based on the draft genome sequence was 72.0 mol%. 16S rRNA gene sequence analysis indicated that strain LHW63021T was a member of the genus Actinomadura and had the highest similarity to Actinomadura echinospora DSM 43163T (97.3 %). Phylogenetic trees supported their close relationship. The average nucleotide identity and digital DNA-DNA hybridization values between the whole genome sequences of strain LHW63021T and A. echinospora DSM 43163T were 79.13 and 23.20 %, respectively. The evidence from the polyphasic study shows that strain LHW63021T represents a novel species of the genus Actinomadura, for which the name Actinomadura craniellae sp. nov. is proposed. The type strain is LHW63021T (=DSM 106125T=CCTCC AA 2018015T).

Dynamic Histological Events and Molecular Changes in Excisional Wound Healing of Diabetic DB/DB Mice.

BACKGROUND: Wound contraction and re-epithelialization over the entire healing process had never been histologically examined daily in diabetic mouse wounds. Correlating morphological characters with molecular changes may be essential to understand the potential mechanism of impeded diabetic wound healing. MATERIALS AND METHODS: In 99 db/db and 63 db/m mice, dorsal-paired 8 mm-diameter wounds were created. Wound contraction and re-epithelialization were histologically analyzed daily-six wounds per group each day. A novel three-dimensional collagen gel model was used to study diabetic dermal fibroblast contractility. Fibroblast-to-myofibroblasts differentiation and TGFß-SMAD signaling pathway through the diabetic db/db wound healing process were studied by immunohistochemistry. RESULTS: Db/db wounds presented delayed closure with impaired wound contraction. Re-epithelialization was not slow but showed thinner epithelial formation and irregular keratinocyte arrangement. Diabetic dermal fibroblasts had significantly lower contractile ability than nondiabetic fibroblasts. In db/db wounds, α-SMA, the marker of myofibroblasts, showed constantly low through the healing, which represented reduced fibroblast-to-myofibroblasts differentiation. Remarkably weak staining of TGFßRI and low accumulation of Smad3 in nuclei were observed. CONCLUSIONS: We demonstrated and precisely located downregulated TGFß signaling pathway in db/db wounds by showing low expression of TGFßRI and failure of Smad3 translocation from cytoplasm to nuclei, which was not reported previously. The downregulated TGFß signaling pathway may contribute to the attenuated fibroblast-to-myofibroblast differentiation. Deficient re-epithelialization and defective wound contraction contribute principally to delayed healing of diabetic db/db wounds.

[Roles and mechanisms of traditional Chinese medicine and its active ingredients in treating epilepsy].

At present,Western medicine is widely used in the treatment of epilepsy.However,about 30%-40% of epileptic patients are resistant to them and are affected by the side effects of these drugs.Traditional Chinese medicine is effective in treating epileptic seizures and relieving complications caused by Western medicine.However,the active ingredients and mechanisms of traditional Chinese medicine remain unclear.This article reviews and summarizes the advances and mechanisms in treating epilepsy,such as Chinese medicine monomer,the extracts of single Chinese medicine and Chinese medicine compound.Chinese medicine monomers,including gastrodin,asarone,rhynchophylline,ligustrazine,tanshinone ⅡA,curcumin,etc.,have antiepileptic effects via regulating excitatory neurotransmitters and receptors,the expression of inflammatory factors,sodium/potassium ion channels and the expression of apoptotic protein,therefore protecting neurons.The extracts of single Chinese herbal including the extracts of Gastrodiae Rhizoma,Acori Tatarinowii Rhizoma,Ginseng Radix et Rhizoma,Ganoderma,Scutellariae Radix and Ginkgo Folium,etc.,have antiepileptic effects related to the inhibition of γ-aminobutyric acid receptor,upregulation of phosphatidylinositol 3-kinase signaling pathway and reduction of glutamate-induced excitotoxicity and oxidative stress response.Furthermore,these extracts can regulate ion channels and reduce oxidative damage of neurons.Chinese medicine compounds including Dianxian Qing Granules,Danxing Ningxian Granules,Huoxue Dingxian formulae,etc.,can improve the therapeutic effect on epilepsy through simultaneously regulating excitatory transmitters,apoptosis factors and cytokines.

Acupoint Autohemotherapy Attenuates DNCB-Induced Atopic Dermatitis and Activates Regulatory T Cells in BALB/c Mice.

Purpose: Acupoint autohemotherapy (A-AHT) has been proposed as an alternative and complementary treatment for atopic dermatitis (AD), yet the exact role of its blood component in terms of therapeutic efficacy and mechanism of action is still largely unknown. Methods: This study aimed to evaluate the therapeutic efficacies and action mechanisms of intramuscular injections of autologous whole blood (AWB) and mouse immunoglobulin G (IgG) (autologous or heterologous) at acupoints on 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse models. Serum levels of total immunoglobulin E (IgE), IgG, interleukin-10 (IL-10), and interferon-gamma (IFN-γ) were measured, as well as mRNA expression levels of Forkhead box P3 (FoxP3), IL-10 and IFN-γ in dorsal skin lesions, and IL-10+, IFN-γ+ and FoxP3+CD4+T cells in murine spleen. Results: It showed that repeated acupoint injection of AWB, autologous total IgG (purified from autologous blood in AD mice) or heterologous total IgG (purified from healthy blood in normal mice) effectively reduced the severity of AD symptoms and decreased epidermal and dermal thickness as well as mast cells in skin lesions. Additionally, AWB acupoint injection was found to upregulate FoxP3+, IL-10+ and IFN-γ+ CD4+T cells in murine spleen, suppressing the production of IgE antibodies and increasing that of IgG antibodies in the serum. Furthermore, both AWB and autologous total IgG administrations significantly elevated FoxP3 expression, mRNA levels of IL-10 and IFN-γ in dorsal skin lesions. However, acupoint injection of heterologous total IgG had no effect on regulatory T (Treg) and Th1 cells modulation. Conclusion: These findings suggest that the therapeutic effects of A-AHT on AD are mediated by IgG-induced activation of Treg cells.

Greater traditionalism predicts COVID-19 precautionary behaviors across 27 societies.

People vary both in their embrace of their society's traditions, and in their perception of hazards as salient and necessitating a response. Over evolutionary time, traditions have offered avenues for addressing hazards, plausibly resulting in linkages between orientations toward tradition and orientations toward danger. Emerging research documents connections between traditionalism and threat responsivity, including pathogen-avoidance motivations. Additionally, because hazard-mitigating behaviors can conflict with competing priorities, associations between traditionalism and pathogen avoidance may hinge on contextually contingent tradeoffs. The COVID-19 pandemic provides a real-world test of the posited relationship between traditionalism and hazard avoidance. Across 27 societies (N = 7844), we find that, in a majority of countries, individuals' endorsement of tradition positively correlates with their adherence to costly COVID-19-avoidance behaviors; accounting for some of the conflicts that arise between public health precautions and other objectives further strengthens this evidence that traditionalism is associated with greater attention to hazards.

Homocysteine-Induced Disturbances in DNA Methylation Contribute to Development of Stress-Associated Cognitive Decline in Rats.

Chronic stress is generally accepted as the main risk factor in the development of cognitive decline; however, the underlying mechanisms remain unclear. Previous data have demonstrated that the levels of homocysteine (Hcy) are significantly elevated in the plasma of stressed animals, which suggests that Hcy is associated with stress and cognitive decline. To test this hypothesis, we analyzed the cognitive function, plasma concentrations of Hcy, and brain-derived neurotropic factor (BDNF) levels in rats undergoing chronic unpredicted mild stress (CUMS). The results showed that decreased cognitive behavioral performance and decreased BDNF transcription and protein expression were correlated with hyperhomocysteinemia (HHcy) levels in stressed rats. Diet-induced HHcy mimicked the cognitive decline and BDNF downregulation in the same manner as CUMS, while Hcy reduction (by means of vitamin B complex supplements) alleviated the cognitive deficits and BDNF reduction in CUMS rats. Furthermore, we also found that both stress and HHcy disturbed the DNA methylation process in the brain and induced DNA hypermethylation in the BDNF promoter. In contrast, control of Hcy blocked BDNF promoter methylation and upregulated BDNF levels in the brain. These results imply the possibility of a causal role of Hcy in stress-induced cognitive decline. We also used ten-eleven translocation (TET1), an enzyme that induces DNA demethylation, to verify the involvement of Hcy and DNA methylation in the regulation of BDNF expression and the development of stress-related cognitive decline. The data showed that TET1-expressing viral injection into the hippocampus inhibited BDNF promoter methylation and significantly mitigated the cognitive decline in HHcy rats. Taken together, novel evidence from the present study suggests that Hcy is likely involved in chronic stress-induced BDNF reduction and related cognitive deficits. In addition, the negative side-effects of HHcy may be associated with Hcy-induced DNA hypermethylation in the BDNF promoter. The results also suggest the possibility of Hcy as a target for therapy and the potential value of vitamin B intake in preventing stress-induced cognitive decline.

Enhancement of flap survival and changes in angiogenic gene expression after AAV2-mediated VEGF gene transfer to rat ischemic flaps.

Necrosis of surgically transferred flaps due to ischemia is a serious wound problem. We evaluated the improvement of flap survival and changes in angiogenic gene expression profiles after transfer of the VEGF gene by means of adeno-associated virus type 2 (AAV2) vector to rat ischemic flaps. Thirty rats were divided into one experimental group, one AAV2-GFP group, and one saline group. AAV2-VEGF or AAV2-GFP were injected intradermally into the rat dorsum in the AAV2-VEGF or AAV2-GFP group. The saline group received saline injection. A 3 × 10 cm flap was raised in each rat two weeks post-injection. One week after surgery, flap viability was evaluated. Angiogenesis real-time PCR array was performed to analyze the expression of angiogenesis-associated genes. The AAV2-VEGF treatment significantly improved flap survival (p<0.05). Immunohistochemical staining showed increased VEGF expression in AAV2-VEGF treated flaps. The PCR array identified remarkable changes in 6 out of the 84 angiogenesis-associated genes in AAV2-VEGF treated flaps. Particularly, EGF, PDGF-A and VEGF-B genes were up-regulated in these flaps. In contrast, FGF2 gene expression was down-regulated. In conclusion, AAV2-VEGF improves flap survival and affects the expression of a series of endogenous growth factor genes, which likely play critical roles in the enhancement of ischemic flap survival.

A meta-analysis of hormone administration effects on cooperative behaviours: Oxytocin, vasopressin, and testosterone.

The hormones oxytocin, vasopressin, and testosterone have been implicated in cooperative behaviours and have attracted increasing research interest for their potential to regulate human cooperation in both healthy and clinical populations. However, the behavioural effects of the administration of these hormones remain to be verified. The current analysis included 41 studies involving 3,269 participants with a narrow age range. We examined the administration effects of these hormones on cooperative behaviour and the regulatory effects of individual characteristics, hormone interventions, and task structure and context. Results revealed a moderate positive effect size of oxytocin intranasal administration, a large negative effect size of vasopressin intranasal administration, and nonsignificant effects of testosterone administration on cooperative behaviours. Participants with mental dysfunctions were less sensitive to oxytocin and vasopressin administration. Oxytocin administration was effective in an in-group situation and for initial choices, corroborating a Tit-for-Tat strategy.

Inverse Correlation Between Distress and Performance in the Medical Rescuers Against COVID-19 in Wuhan.

Background: During the COVID-19 pandemic, the Chinese government had transferred many medical rescuers to Wuhan, which provided effective support in disease control. The high-intensity working and mental stress during rescue could induce distress and negatively impact the performance of rescuer afterward. Materials and Methods: To identify the characteristics of stress load and its possible effects on performance, the study surveyed 90 medical rescuers in Wuhan using a mobile phone-based self-rated questionnaire. Results: The results showed an existence of universal but mostly mild distress in rescuers. About 95.6% of the participants reported that they had at least one symptom of distress, whereas, the median scores were <30 (100 as max). Compared with civilian rescuers, a higher proportion of working with immediate virus contact was found in military medical rescuers (P = 0.008); however, no statistical differences of stress load were found between civilians and militaries. The rescuers with positive cognition or good psychological preparation were found having lower stress loads than other rescuers. An inverse correlation between the stress load and performance (R = -0.24, P = 0.023) and a positive correlation between social support and working performance (R = 0.349, P = 0.001) were found in our survey, suggesting the possible negative effects of stress and the beneficial effects of social support on performance. Conclusion: Our study indicated that more attention should be paid to the distress of medical rescuers against COVID-19. Positive cognitions, good psychological preparations, and sufficient social support would be necessary to reduce the distress and improve the performance in COVID-19 rescue.

Molecular events of cellular apoptosis and proliferation in the early tendon healing period.

PURPOSE: Cellular proliferation is accompanied by cellular apoptosis. In the healing digital flexor tendon, molecular events concerning cellular apoptosis have not been investigated. This study aimed to investigate the relationship between cellular apoptosis and proliferation in early tendon healing. METHODS: The flexor digitorum profundus tendons of 50 long toes in 25 chickens were transected and were repaired surgically. On postoperative days 3, 7, 14, 21, and 28, we subjected tendons to in situ terminal deoxynucleotide transferase dUTP nick end labeling (TUNEL) assay to detect apoptotic cells, immunofluorescence staining with antibodies to proliferating cell nuclear antigen to assess proliferation, and Bcl-2, an anti-apoptotic protein, to assess responses suppressive to apoptosis. The positively labeled tenocytes were counted microscopically and compared statistically. We also stained sections with hematoxylin and eosin to observe their healing status. An additional 12 tendons (6 chickens) served as day 0 controls. RESULTS: Compared with tendons at day 0, the healing tendons had notably greater cellularity in both epitenon and endotenon areas. The total number of cells and number of TUNEL-positive cells peaked at day 3. At days 7 to 21, the number of proliferating cell nuclear antigen-positive cells peaked. At days 7 and 14, the cells positively stained with Bcl-2 peaked. At days 14 to 28, the total number of cells and TUNEL-positive cells decreased significantly compared with those at days 3 and 7, yet the numbers remained greater than those on day 0. CONCLUSIONS: Apoptosis in the healing tendons peaks at day 3, followed about 10 days later by the peak proliferation period. Because Bcl-2 serves to inhibit apoptosis, a later increase in Bcl-2-positive cells indicates that tendon apoptosis is inhibited. These findings indicate that tenocyte apoptosis is accelerated within several days after injury, followed by increases in cellular proliferation and activation of molecular events to inhibit apoptosis in 2 to 4 weeks.

Robust detection of neural spikes using sparse coding based features.

The detection of neural spikes plays an important role in studying and processing extracellular recording signals, which promises to be able to extract the necessary spike data for all subsequent analyses. The existing algorithms for spike detection have achieved great progress but there still remains much room for improvement in terms of the robustness to noise and the flexibility in the spike shape. To address this issue, this paper presents a novel method for spike detection based on the theory of sparse representation. By analyzing the characteristics of extracellular neural recordings, a targetdriven sparse representation framework is firstly constructed, with which the neural spike signals can be effectively separated from background noise. In addition, considering the fact that the spikes emitted by different neurons have different shapes, we then learn a universal dictionary to give a sparse representation of various spike signals. Finally, the information (location and number) of spikes in the recorded signal are achieved by comprehensively analyzing the sparse features. Experimental results demonstrate that the proposed method outperforms the existing methods in the spike detection problem.

GluR6-containing KA receptor mediates the activation of p38 MAP kinase in rat hippocampal CA1 region during brain ischemia injury.

Our previous study showed that kainate (KA) receptor subunit GluR6 played an important role in ischemia-induced MLK3 and JNK activation and neuronal degeneration through the GluR6-PSD95-MLK3 signaling module. However, whether the KA receptors subunit GluR6 is involved in the activation of p38 MAP kinase during the transient brain ischemia/reperfusion (I/R) in the rat hippocampal CA1 subfield is still unknown. In this present study, we first evaluated the time-course of phospho-p38 MAP kinase at various time-points after 15 min of ischemia and then observed the effects of antagonist of KA receptor subunit GluR6, GluR6 antisence oligodeoxynucleotides on the phosphorylation of p38 MAP kinase induced by I/R. Results showed that inhibiting KA receptor GluR6 or suppressing the expression of KA receptor GluR6 could down-regulate the elevation of phospho-p38 MAP kinase induced by I/R. These drugs also reduced the phosphorylation of MLK3, MKK3/MKK6, MKK4, and MAPKAPK2. Additionally, our results indicated administration of three drugs, including p38 MAP kinase inhibitor before brain ischemia significantly decreased the number of TUNEL-positive cells detected at 3 days of reperfusion and increased the number of the surviving CA1 pyramidal cells at 5 days of reperfusion after 15 min of ischemia. Taken together, we suggest that GluR6-contained KA receptors can mediate p38 MAP kinase activation through a kinase cascade, including MLK3, MKK3/MKK6, and MKK4 and then induce increased phosphorylation of MAPKAPK-2 during ischemia injury and ultimately result in neuronal cell death in the rat hippocampal CA1 region.

Application of AAV2-mediated bFGF gene therapy on survival of ischemic flaps: effects of timing of gene transfer.

Necrosis of surgically transferred flaps is a major problem in reconstructive surgery. We investigated efficacy of a new vector system-adeno-associated viral 2 (AAV2)-mediated bFGF gene transfer to enhance survival of the ischemic flap. Thirty-eight Sprague-Dawley rats were divided into 3 gene therapy groups and 1 nontreated control of 9 or 10 each. 7.5 x 10(10) AAV2-bFGF viral particles were injected to the dorsum of each of the 29 rats; these rats were divided into 3 groups according to the timing of flap elevation. At the time of surgery, 1 week, and 2 weeks after surgery, flaps of 3 x 7 cm were raised. One week after surgery, flap viability was measured. Vascularization and immunohistochemical staining of the bFGF were evaluated of histologic sections. Flap viability was significantly improved by the AAV2-bFGF gene therapy at the time of surgery, and the flaps with the greatest survival area were found in the rats injected with AAV2-bFGF, 2 weeks before surgery. However, flap viability was significantly decreased by the gene therapy 1 week before surgery. Histologically, vascularity was increased in the groups with AAV2-bFGF injection and immunohistochemical staining showed greatly enhanced bFGF expression by gene transfer. The novel approach of AAV2-bFGF gene therapy shows encouraging manifestations in improving survival of flaps when the flaps are prefabricated during or 2 weeks before surgery.

Membrane-bound IgE on B cells is increased during Clonorchis sinensis infection.

A high level of serum IgE is a hallmark of helminthic disease. Secretory IgE can bind FcεRI or FcεRII/CD23. The combination of IgE and FcεRI, a high-affinity interaction, has long received attention and is believed to facilitate helminth control, while the properties of CD23-bound IgE have long been unexplored. Here, we established a Clonorchis sinensis (C. sinensis) infection model with different mouse strains and investigated membrane-bound IgE on B cells during infection. We show that after infection, the increase in CD23 expression on B cells was obvious, even in relatively resistant C57BL/6 mice, as well as in susceptible BALB/c and FVB mice. Although the serum IgE amount was lower in C57BL/6 mice than in BALB/c and FVB mice, the level of IgE binding to peripheral B cells was also elevated. Additionally, the IgE on B cells was soon undetectable in vitro due to dissociable binding. The results of the present study demonstrate the dramatic increase in CD23-bound IgE on B cells after C. sinensis infection. The significance of CD23-bound IgE in Ag transport and presentation has gained consideration in allergy development for its potential ability to promote the Th2 response. Therefore, even though the association of IgE and CD23 is not as substantial as that of IgE and FcεRI, membrane-bound IgE on B cells may be worth further study regarding clonorchiasis and other parasitic infections.

Risk communication and risky choice in context: ambiguity and ambivalence hypothesis.

This chapter takes a synthetic approach to six related lines of research on decision making at risk and views risky choice as a function of cue use with priorities in the context of risk communication. An evolutionary analysis of risk and risk communication is presented in which risk is defined not only as variance in monetary payoff but also as variance in biological relatedness, social relations, and ultimately in reproductive fitness. Empirical evidence of ecological and social significance embedded in risk messages is analyzed, and how these risk cues affect behavioral decision making is examined. A new explanatory framework, the ambiguity and ambivalence hypothesis, identifies two key preconditions contributing to inconsistency and biases in making risky choices as a result of cue use in the course of risk communication.

Opposing effects of Bad phosphorylation at two distinct sites by Akt1 and JNK1/2 on ischemic brain injury.

Increasing evidence suggests that the Bcl-2 family proteins play pivotal roles in regulation of the mitochondria cell-death pathway on transient cerebral ischemia. Bad, a BH3-only proapoptotic Bcl-2 family protein, has been shown to be phosphorylated extensively on serine by kinds of kinases. However, the exact mechanisms of the upstream kinases in regulation of Bad signaling pathway remain unknown. Here, we reported that Bad could be phosphorylated not only by Akt1 but also by JNK1/2 after transient global ischemia in rat hippocampal CA1 region. Our data demonstrated that Akt1 mediated the phosphorylation of Bad at serine 136, which increased the interaction of serine 136-phosphorylated Bad with 14-3-3 proteins and prevented the dimerization of Bad with Bcl-Xl, inhibited the release of cytochrome c to the cytosol and the death effector caspase-3 activation, leading to the survival of neuron. In contrast, JNK1/2 induced the phosphorylation of Bad at a novel site of serine 128 after brain ischemia/reperfusion, which inhibited the interaction of PI3K/Akt-induced serine 136-phosphorylated Bad with 14-3-3 proteins, thereby promoted the apoptotic effect of Bad. In addition, activated Akt1 inhibited the activation of Bad(S128) through downregulating JNK1/2 activation, thus inhibiting JNK-mediated Bad apoptosis pathway. Furthermore, the fate of cell to survive or to die was determined by a balance between prosurvival and proapoptotic signals. Taken together, our studies reveal that Bad phosphorylation at two distinct sites induced by Akt1 and JNK1/2 have opposing effects on ischemic brain injury, and present the possibility of Bad as a potential therapeutic target for stroke treatment.

Resource Signaling via Blood Glucose in Embodied Decision Making.

Food, money, and time are exchangeable resources essential for survival and reproduction. Individuals live within finite budgets of these resources and make tradeoffs between money and time when making intertemporal choices between an immediate smaller reward and a delayed lager reward. In this paper, I examine signaling functions of blood glucose in regulating behaviors related to resource regulations beyond caloric metabolisms. These behavioral regulations include choices between energy expenditure and energy conservation, monetary intertemporal choices, and self-control in overcoming temptations. I begin by comparing potential embodied signals for resource forecasting and proactive decision making in terms of their pros and cons as a signal for regulating both metabolism and behavioral decision making and self-control. Based on this analysis, circulating glucose emerges as not only the designated fuel for brain metabolism but also a privileged resource forecasting signal for regulating immediate, short-term, and long-term behavioral adaptations to the resource budget of the decision maker. In the context of an on-going debate between the limited resource model and the motivation accounts of behavioral effects of blood glucose, I propose a dual functions (caloric provision and resource forecasting) and dual signaling (glucose taste and ingestion) hypothesis of circulating glucose in resource management, and provide behavioral and neurophysiological evidence of the separate effects of glucose taste to motivate effort for resource acquisition and glucose ingestion to promote resource conservation and future orientation. Accumulating evidence indicates that the body is able to detect fake signals of non-caloric sweeteners and react to such "caloric crisis" with an enhanced preference for immediate rewards over future rewards, revealing the wisdom of the body.