Triad3a induces the degradation of early necrosome to limit RipK1-dependent cytokine production and necroptosis.

Understanding the molecular signaling in programmed cell death is vital to a practical understanding of inflammation and immune cell function. Here we identify a previously unrecognized mechanism that functions to downregulate the necrosome, a central signaling complex involved in inflammation and necroptosis. We show that RipK1 associates with RipK3 in an early necrosome, independent of RipK3 phosphorylation and MLKL-induced necroptotic death. We find that formation of the early necrosome activates K48-ubiquitin-dependent proteasomal degradation of RipK1, Caspase-8, and other necrosomal proteins. Our results reveal that the E3-ubiquitin ligase Triad3a promotes this negative feedback loop independently of typical RipK1 ubiquitin editing enzymes, cIAPs, A20, or CYLD. Finally, we show that Triad3a-dependent necrosomal degradation limits necroptosis and production of inflammatory cytokines. These results reveal a new mechanism of shutting off necrosome signaling and may pave the way to new strategies for therapeutic manipulation of inflammatory responses

Observation of a ppb mass threshoud enhancement in \psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) decay

The decay channel $\psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p})$ is studied using a sample of $1.06\times 10^8$ $\psi^\prime$ events collected by the BESIII experiment at BEPCII. A strong enhancement at threshold is observed in the $p\bar{p}$ invariant mass spectrum. The enhancement can be fit with an $S$-wave Breit-Wigner resonance function with a resulting peak mass of $M=1861^{+6}_{-13} {\rm (stat)}^{+7}_{-26} {\rm (syst)} {\rm MeV/}c^2$ and a narrow width that is $\Gamma<38 {\rm MeV/}c^2$ at the 90% confidence level. These results are consistent with published BESII results. These mass and width values do not match with those of any known meson resonance.Comment: 5 pages, 3 figures, submitted to Chinese Physics

Y-Chromosome Evidence for Common Ancestry of Three Chinese Populations with a High Risk of Esophageal Cancer

High rates of esophageal cancer (EC) are found in people of the Henan Taihang Mountain, Fujian Minnan, and Chaoshan regions of China. Historical records describe great waves of populations migrating from north-central China (the Henan and Shanxi Hans) through coastal Fujian Province to the Chaoshan plain. Although these regions are geographically distant, we hypothesized that EC high-risk populations in these three areas could share a common ancestry. Accordingly, we used 16 East Asian-specific Y-chromosome biallelic markers (single nucleotide polymorphisms; Y-SNPs) and six Y-chromosome short tandem repeat (Y-STR) loci to infer the origin of the EC high-risk Chaoshan population (CSP) and the genetic relationship between the CSP and the EC high-risk Henan Taihang Mountain population (HTMP) and Fujian population (FJP). The predominant haplogroups in these three populations are O3*, O3e*, and O3e1, with no significant difference between the populations in the frequency of these genotypes. Frequency distribution and principal component analysis revealed that the CSP is closely related to the HTMP and FJP, even though the former is geographically nearer to other populations (Guangfu and Hakka clans). The FJP is between the CSP and HTMP in the principal component plot. The CSP, FJP and HTMP are more closely related to Chinese Hans than to minorities, except Manchu Chinese, and are descendants of Sino-Tibetans, not Baiyues. Correlation analysis, hierarchical clustering analysis, and phylogenetic analysis (neighbor-joining tree) all support close genetic relatedness among the CSP, FJP and HTMP. The network for haplogroup O3 (including O3*, O3e* and O3e1) showed that the HTMP have highest STR haplotype diversity, suggesting that the HTMP may be a progenitor population for the CSP and FJP. These findings support the potentially important role of shared ancestry in understanding more about the genetic susceptibility in EC etiology in high-risk populations and have implications for determining the molecular basis of this disease

Cognitive and Psychological Reactions of the General Population Three Months After the 2011 Tohoku Earthquake and Tsunami

BACKGROUND: The largest earthquake on record in Japan (magnitude 9.0) occurred on March 11, 2011, and the subsequent tsunami devastated the Pacific coast of Northern Japan. These further triggered the Fukushima I nuclear power plant accidents. Such a hugely complex disaster inevitably has negative psychological effects on general populations as well as on the direct victims. While previous disaster studies enrolled descriptive approaches focusing on direct victims, the structure of the psychological adjustment process of people from the general population has remained uncertain. The current study attempted to establish a path model that sufficiently reflects the early psychological adaptation process of the general population to large-scale natural disasters. METHODS AND FINDINGS: Participants from the primary disaster area (n = 1083) and other areas (n = 2372) voluntarily participated in an online questionnaire study. By constructing path models using a structural equation model procedure (SEM), we examined the structural relationship among psychological constructs known related to disasters. As post-traumatic stress symptoms (PTS) were significantly more present in people in the primarily affected area than in those in secondary- or non-affected areas, the path models were constructed for the primary victims. The parsimoniously depicted model with the best fit was achieved for the psychological-adjustment centered model with quality of life (QoL) as a final outcome. CONCLUSION: The paths to QoL via negative routes (from negative cognitive appraisal, PTS, and general stress) were dominant, suggesting the importance of clinical intervention for reducing negative cognitive appraisal, and for caring for general stress and PTS to maintain QoL at an early stage of psychological adaptation to a disaster. The model also depicted the presence of a positive route where positive cognitive appraisal facilitates post-traumatic growth (PTG) to achieve a higher QoL, suggesting the potential importance of positive psychological preventive care for unexpected natural disasters

Sensitivity of jarrah (Eucalyptus marginata) to phosphate, phosphite, and arsenate pulses as influenced by fungal symbiotic associations

Many plant species adapted to P-impoverished soils, including jarrah (Eucalyptus marginata), develop toxicity symptoms when exposed to high doses of phosphate (Pi) and its analogs such as phosphite (Phi) and arsenate (AsV). The present study was undertaken to investigate the effects of fungal symbionts Scutellospora calospora, Scleroderma sp., and Austroboletus occidentalis on the response of jarrah to highly toxic pulses (1.5 mmol kg−1 soil) of Pi, Phi, and AsV. S. calospora formed an arbuscular mycorrhizal (AM) symbiosis while both Scleroderma sp. and A. occidentalis established a non-colonizing symbiosis with jarrah plants. All these interactions significantly improved jarrah growth and Pi uptake under P-limiting conditions. The AM fungal colonization naturally declines in AM-eucalypt symbioses after 2–3 months; however, in the present study, the high Pi pulse inhibited the decline of AM fungal colonization in jarrah. Four weeks after exposure to the Pi pulse, plants inoculated with S. calospora had significantly lower toxicity symptoms compared to non-mycorrhizal (NM) plants, and all fungal treatments induced tolerance against Phi toxicity in jarrah. However, no tolerance was observed for AsV-treated plants even though all inoculated plants had significantly lower shoot As concentrations than the NM plants. The transcript profile of five jarrah high-affinity phosphate transporter (PHT1 family) genes in roots was not altered in response to any of the fungal species tested. Interestingly, plants exposed to high Pi supplies for 1 day did not have reduced transcript levels for any of the five PHT1 genes in roots, and transcript abundance of four PHT1 genes actually increased. It is therefore suggested that jarrah, and perhaps other P-sensitive perennial species, respond positively to Pi available in the soil solution through increasing rather than decreasing the expression of selected PHT1 genes. Furthermore, Scleroderma sp. can be considered as a fungus with dual functional capacity capable of forming both ectomycorrhizal and non-colonizing associations, where both pathways are always accompanied by evident growth and nutritional benefits

AMP-activated protein kinase inhibits NF-κB signaling and inflammation: impact on healthspan and lifespan

Adenosine monophosphate-activated protein kinase (AMPK) is a crucial regulator of energy metabolic homeostasis and thus a major survival factor in a variety of metabolic stresses and also in the aging process. Metabolic syndrome is associated with a low-grade, chronic inflammation, primarily in adipose tissue. A low-level of inflammation is also present in the aging process. There are emerging results indicating that AMPK signaling can inhibit the inflammatory responses induced by the nuclear factor-κB (NF-κB) system. The NF-κB subunits are not direct phosphorylation targets of AMPK, but the inhibition of NF-κB signaling is mediated by several downstream targets of AMPK, e.g., SIRT1, PGC-1α, p53, and Forkhead box O (FoxO) factors. AMPK signaling seems to enhance energy metabolism while it can repress inflammatory responses linked to chronic stress, e.g., in nutritional overload and during the aging process. AMPK can inhibit endoplasmic reticulum and oxidative stresses which are involved in metabolic disorders and the aging process. Interestingly, many target proteins of AMPK are so-called longevity factors, e.g., SIRT1, p53, and FoxOs, which not only can increase the stress resistance and extend the lifespan of many organisms but also inhibit the inflammatory responses. The activation capacity of AMPK declines in metabolic stress and with aging which could augment the metabolic diseases and accelerate the aging process. We will review the AMPK pathways involved in the inhibition of NF-κB signaling and suppression of inflammation. We also emphasize that the capacity of AMPK to repress inflammatory responses can have a significant impact on both healthspan and lifespan

Measurement of the matrix element for the decay η′→ηπ +π -

The Dalitz plot of η⊃′→ηπ⊃+π⊃- decay is studied using (225.2±2.8)×106 J/ψ events collected with the BESIII detector at the BEPCII e⊃+e⊃- collider. With the largest sample of η⊃′ decays to date, the parameters of the Dalitz plot are determined in a generalized and a linear representation. Also, the branching fraction of J/ψ→γη⊃′ is determined to be (4.84±0.03±0.24)×10⊃-3, where the first error is statistical and the second systematic. © 2011 American Physical Society.published_or_final_versio

First observation of the decays χcJ→π0π0π0π0

We present a study of the P-wave spin-triplet charmonium χ cJ decays (J=0, 1, 2) into π0π0π0π0. The analysis is based on 106×106 ψ⊃′ decays recorded with the BESIII detector at the BEPCII electron positron collider. The decay into the π0π0π0π0 hadronic final state is observed for the first time. We measure the branching fractions B(χ c0→π0π0π0π0)=(3.34±0. 06±0.44)×10⊃-3, B(χ c1→π0π0π0π0) =(0.57±0.03±0.08)×10⊃-3, and B(χ c2→π0π0π0π0)=(1.21±0.05±0.16) ×10⊃-3, where the uncertainties are statistical and systematical, respectively. © 2011 American Physical Society.published_or_final_versio