Glycine Potentiates AMPA Receptor Function through Metabotropic Activation of GIuN2A-Containing NMDA Receptors

NMDA receptors are Ca2+.-permeable ion channels. The activation of NMDA receptors requires agonist glutamate and co-agonist glycine. Recent evidence indicates that NMDA receptor also has metabotropic function. Here we report that in cultured mouse hippocampal neurons, glycine increases AMPA receptor -mediated currents independent of the channel activity of NMDA receptors and the activation of glycine receptors. The potentiation of AMPA receptor function by glycine is antagonized by the inhibition of ERK1/2. In the hippocampal neurons and in the HEK293 cells transfected with different combinations of NMDA receptors, glycine preferentially acts on GIuN2A-containing NMDA receptors (GIuN2ARs), but not GIuN2B-containing NMDA receptors (GIuN2BRs), to enhance ERK1/2 phosphorylation independent of the channel activity of GIuN2ARs. Without requiring the channel activity of GIuN2ARs, glycine increases AMPA receptor -mediated currents through GIuN2ARs. Thus, these results reveal a metabotropic function of GIuN2ARs in mediating glycine-induced potentiation of AMPA receptor function via ERK1/2 activation

Genome based cell population heterogeneity promotes tumorigenicity: the evolutionary mechanism of cancer.

Cancer progression represents an evolutionary process where overall genome level changes reflect system instability and serve as a driving force for evolving new systems. To illustrate this principle it must be demonstrated that karyotypic heterogeneity (population diversity) directly contributes to tumorigenicity. Five well characterized in vitro tumor progression models representing various types of cancers were selected for such an analysis. The tumorigenicity of each model has been linked to different molecular pathways, and there is no common molecular mechanism shared among them. According to our hypothesis that genome level heterogeneity is a key to cancer evolution, we expect to reveal that the common link of tumorigenicity between these diverse models is elevated genome diversity. Spectral karyotyping (SKY) was used to compare the degree of karyotypic heterogeneity displayed in various sublines of these five models. The cell population diversity was determined by scoring type and frequencies of clonal and non-clonal chromosome aberrations (CCAs and NCCAs). The tumorigenicity of these models has been separately analyzed. As expected, the highest level of NCCAs was detected coupled with the strongest tumorigenicity among all models analyzed. The karyotypic heterogeneity of both benign hyperplastic lesions and premalignant dysplastic tissues were further analyzed to support this conclusion. This common link between elevated NCCAs and increased tumorigenicity suggests an evolutionary causative relationship between system instability, population diversity, and cancer evolution. This study reconciles the difference between evolutionary and molecular mechanisms of cancer and suggests that NCCAs can serve as a biomarker to monitor the probability of cancer progression

The relationship between anesthesia, surgery and postoperative immune function in cancer patients: a review

This review comprehensively examines the impact of anesthesia and surgical interventions on the immune function of cancer patients postoperatively. Recent studies have shown that surgery and its accompanying anesthesia management can significantly influence immune function in cancer patients, potentially affecting their prognosis. This review synthesizes clinical studies and basic research to summarize the specific effects of anesthesia methods, drugs, postoperative analgesia, intraoperative transfusion, surgical techniques, and trauma extent on the immune function of cancer patients post-surgery. Additionally, this review discusses optimization strategies based on current research, aiming to refine anesthesia and surgical management to maximize the preservation and enhancement of postoperative immune function in cancer patients, with the potential to improve clinical outcomes

Chinese Wheat Mosaic Virus-Induced Gene Silencing in Monocots and Dicots at Low Temperature

Virus-induced gene silencing (VIGS) is an important tool for functional genomics studies in plants. With this method, it is possible to target most endogenous genes and downregulate the messenger RNA (mRNA) in a sequence-specific manner. Chinese wheat mosaic virus (CWMV) has a bipartite, single-strand positive RNA genome, and can infect both wheat and Nicotiana benthamiana, and the optimal temperature for systemic infection in plants is 17°C. To assess the potential of the virus as a vector for gene silencing at low temperature, a fragment of the N. benthamiana or wheat phytoene desaturase (PDS) gene was expressed from a modified CWMV RNA2 clone and the resulting photo bleaching in infected plants was used as a reporter for silencing. Downregulation of PDS mRNA was also measured by quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR). In experiments using fragments of PDS ranging from 500 to 1500 nucleotides, insert length influenced the stability and the efficiency of VIGS. The CWMV induced silencing system was also used to suppress miR165/166 and miR3134a through expression of miRNA target mimics. The relative expression levels of mature miR165/166 and miR3134a decreased whereas the transcript levels of their target genes increased. Interestingly, we also found the CWMV-induced silencing system was more efficient compare with the vector based on Barley stripe mosaic virus (BSMV) or Foxtail mosaic virus (FoMV) in wheat or the vector based on TRV in N. benthamiana at 17°C. In summary, the CWMV vector is effective in silencing endogenous genes and miRNAs at 17°C, thereby providing a powerful tool for gene function analysis in both N. benthamiana and wheat at low temperature

Direct Measurements of Absolute Branching Fractions for D0 and D+ Inclusive Semimuonic Decays

By analyzing about 33 $\rm pb^{-1}$ data sample collected at and around 3.773 GeV with the BES-II detector at the BEPC collider, we directly measure the branching fractions for the neutral and charged $D$ inclusive semimuonic decays to be $BF(D^0 \to \mu^+ X) =(6.8\pm 1.5\pm 0.7)$ and $BF(D^+ \to \mu^+ X) =(17.6 \pm 2.7 \pm 1.8)$, and determine the ratio of the two branching fractions to be $\frac{BF(D^+ \to \mu^+ X)}{BF(D^0 \to \mu^+ X)}=2.59\pm 0.70 \pm 0.25$

The CDEX-1 1 kg Point-Contact Germanium Detector for Low Mass Dark Matter Searches

The CDEX Collaboration has been established for direct detection of light dark matter particles, using ultra-low energy threshold p-type point-contact germanium detectors, in China JinPing underground Laboratory (CJPL). The first 1 kg point-contact germanium detector with a sub-keV energy threshold has been tested in a passive shielding system located in CJPL. The outputs from both the point-contact p+ electrode and the outside n+ electrode make it possible to scan the lower energy range of less than 1 keV and at the same time to detect the higher energy range up to 3 MeV. The outputs from both p+ and n+ electrode may also provide a more powerful method for signal discrimination for dark matter experiment. Some key parameters, including energy resolution, dead time, decay times of internal X-rays, and system stability, have been tested and measured. The results show that the 1 kg point-contact germanium detector, together with its shielding system and electronics, can run smoothly with good performances. This detector system will be deployed for dark matter search experiments.Comment: 6 pages, 8 figure

Measurement of branching fractions for the inclusive Cabibbo-favored ~K*0(892) and Cabibbo-suppressed K*0(892) decays of neutral and charged D mesons

The branching fractions for the inclusive Cabibbo-favored ~K*0 and Cabibbo-suppressed K*0 decays of D mesons are measured based on a data sample of 33 pb-1 collected at and around the center-of-mass energy of 3.773 GeV with the BES-II detector at the BEPC collider. The branching fractions for the decays D+(0) -> ~K*0(892)X and D0 -> K*0(892)X are determined to be BF(D0 -> \~K*0X) = (8.7 +/- 4.0 +/- 1.2)%, BF(D+ -> ~K*0X) = (23.2 +/- 4.5 +/- 3.0)% and BF(D0 -> K*0X) = (2.8 +/- 1.2 +/- 0.4)%. An upper limit on the branching fraction at 90% C.L. for the decay D+ -> K*0(892)X is set to be BF(D+ -> K*0X) < 6.6%

Direct Measurements of the Branching Fractions for D0→K−e+νeD^0 \to K^-e^+\nu_e and D0→π−e+νeD^0 \to \pi^-e^+\nu_e and Determinations of the Form Factors f+K(0)f_{+}^{K}(0) and f+π(0)f^{\pi}_{+}(0)

The absolute branching fractions for the decays $D^0 \to K^-e ^+\nu_e$ and $D^0 \to \pi^-e^+\nu_e$ are determined using $7584\pm 198 \pm 341$ singly tagged $\bar D^0$ sample from the data collected around 3.773 GeV with the BES-II detector at the BEPC. In the system recoiling against the singly tagged $\bar D^0$ meson, $104.0\pm 10.9$ events for $D^0 \to K^-e ^+\nu_e$ and $9.0 \pm 3.6$ events for $D^0 \to \pi^-e^+\nu_e$ decays are observed. Those yield the absolute branching fractions to be $BF(D^0 \to K^-e^+\nu_e)=(3.82 \pm 0.40\pm 0.27)$ and $BF(D^0 \to \pi^-e^+\nu_e)=(0.33 \pm 0.13\pm 0.03)$. The vector form factors are determined to be $|f^K_+(0)| = 0.78 \pm 0.04 \pm 0.03$ and $|f^{\pi}_+(0)| = 0.73 \pm 0.14 \pm 0.06$. The ratio of the two form factors is measured to be $|f^{\pi}_+(0)/f^K_+(0)|= 0.93 \pm 0.19 \pm 0.07$.Comment: 6 pages, 5 figure

Measurements of the observed cross sections for e+e−→e^+e^-\to exclusive light hadrons containing π0π0\pi^0\pi^0 at s=3.773\sqrt s= 3.773, 3.650 and 3.6648 GeV

By analyzing the data sets of 17.3, 6.5 and 1.0 pb$^{-1}$ taken, respectively, at $\sqrt s= 3.773$, 3.650 and 3.6648 GeV with the BES-II detector at the BEPC collider, we measure the observed cross sections for $e^+e^-\to \pi^+\pi^-\pi^0\pi^0$, $K^+K^-\pi^0\pi^0$, $2(\pi^+\pi^-\pi^0)$, $K^+K^-\pi^+\pi^-\pi^0\pi^0$ and $3(\pi^+\pi^-)\pi^0\pi^0$ at the three energy points. Based on these cross sections we set the upper limits on the observed cross sections and the branching fractions for $\psi(3770)$ decay into these final states at 90% C.L..Comment: 7 pages, 2 figure