Enterovirus 71 induces degradation of TRIM38, a potential E3 ubiquitin ligase

<p>Abstract</p> <p>Background</p> <p>The tripartite motif (TRIM) proteins are a family of more than 70 members in human. However, only a few of them have been well studied. The TRIM proteins contain the conserved RING, B-box, coiled-coil, and SPRY domains, most of which are involved in protein ubiquitination. TRIM38 is a member of the TRIM protein family, which we studied in more detail here as its functions are largely unknown.</p> <p>Results</p> <p>Our study shows that, similar to other TRIM family members, TRIM38 is localized in the cytoplasm. TRIM38 increases ubiquitination of other cellular proteins and catalyzes self-ubiquitination. TRIM38 also promotes K63- and K48-linked ubiquitination of cellular proteins. An intact RING domain is important for the functions of TRIM38. In addition, enterovirus 71 infection induces TRIM38 degradation.</p> <p>Conclusions</p> <p>Our observations demonstrate that TRIM38 has E3 ubiquitin ligase activity and can be degraded during virus infection. These findings may provide insight into innate immune signaling pathways.</p

Distinct double flower varieties in Camellia japonica exhibit both expansion and contraction of C-class gene expression

Double flower domestication is of great value in ornamental plants and presents an excellent system to study the mechanism of morphological alterations by human selection. The classic ABC model provides a genetic framework underlying the control of floral organ identity and organogenesis from which key regulators have been identified and evaluated in many plant species. Recent molecular studies have underscored the importance of C-class homeotic genes, whose functional attenuation contributed to the floral diversity in various species. Cultivated Camellia japonica L. possesses several types of double flowers, however the molecular mechanism underlying their floral morphological diversification remains unclear. In this study, we cloned the C-class orthologous gene CjAG in C. japonica. We analyzed the expression patterns of CjAG in wild C. japonica, and performed ectopic expression in Arabidopsis. These results revealed that CjAG shared conserved C-class function that controls stamen and carpel development. Further we analyzed the expression pattern of CjAG in two different C. japonica double-flower varieties, `Shibaxueshi’ and `Jinpanlizhi’, and showed that expression of CjAG was highly contracted in `Shibaxueshi’ but expanded in inner petals of `Jinpanlizhi’. Moreover, detailed expression analyses of B- and C-class genes have uncovered differential patterns of B-class genes in the inner organs of `Jinpanlizhi’. These results demonstrated that the contraction and expansion of CjAG expression were associated with the formation of different types of double flowers. Our studies have manifested two different trajectories of double flower domestication regarding the C-class gene expression in C. japonica.https://doi.org/10.1186/s12870-014-0288-

Plin4-Dependent Lipid Droplets Hamper Neuronal Mitophagy in the MPTP/p-Induced Mouse Model of Parkinson’s Disease

Epidemiological studies have shown that both lipid metabolism disorder and mitochondrial dysfunction are correlated with the pathogenesis of neurodegenerative diseases (NDDs), including Parkinson’s disease (PD). Emerging evidence suggests that deposition of intracellular lipid droplets (LDs) participates in lipotoxicity and precedes neurodegeneration. Perilipin family members were recognized to facilitate LD movement and cellular signaling interactions. However, the direct interaction between Perilipin-regulated LD deposition and mitochondrial dysfunction in dopaminergic (DA) neurons remains obscure. Here, we demonstrate a novel type of lipid dysregulation involved in PD progression as evidenced by upregulated expression of Plin4 (a coating protein and regulator of LDs), and increased intracellular LD deposition that correlated with the loss of TH-ir (Tyrosine hydroxylase-immunoreactive) neurons in the MPTP/p-induced PD model mouse mesencephalon. Further, in vitro experiments showed that inhibition of LD storage by downregulating Plin4 promoted survival of SH-SY5Y cells. Mechanistically, reduced LD storage restored autophagy, leading to alleviation of mitochondrial damage, which in turn promoted cell survival. Moreover, the parkin-poly-Ub-p62 pathway was involved in this Plin4/LD-induced inhibition of mitophagy. These findings were further confirmed in primary cultures of DA-nergic neurons, in which autophagy inhibitor treatment significantly countermanded the ameliorations conferred by Plin4 silencing. Collectively, these experiments demonstrate that a dysfunctional Plin4/LD/mitophagy axis is involved in PD pathology and suggest Plin4-LDs as a potential biomarker as well as therapeutic strategy for PD

Light absorption enhancement of black carbon in urban Beijing in summer

The light absorption enhancement (E-abs) of black carbon (BC) caused by non-BC materials is an important source of uncertainty in radiative forcing estimate, yet remains poorly understood in relatively polluted environment such as the megacity Beijing. Here BC absorption enhancement at 630 nm was in-situ measured using a ther-modenuder coupled with a soot particle aerosol mass spectrometer and a single scattering albedo monitor in Beijing in summer. The project average (+/- 1 sigma) E-abs was 1.59 ( +/- 0.26), suggesting a significant amplification of BC absorption due to coating materials. E-abs presented a clear daytime increase due to enhanced photochemical processing, and a strong dependence on the mass ratios of non-BC coatings to BC (R-BC). Our results showed that the increase in E(abs )as a function of R-BC was mainly caused by the increased contributions of secondary aerosol. Further analysis showed that the BC absorption enhancement in summer in Beijing was mainly associated with secondary formation of nitrate, sulfate and highly oxidized secondary organic aerosol (SOA), while the formation of freshly and less oxidized SOA appeared not to play an important role.Peer reviewe

Occupational exposure in swine farm defines human skin and nasal microbiota

Anthropogenic environments take an active part in shaping the human microbiome. Herein, we studied skin and nasal microbiota dynamics in response to the exposure in confined and controlled swine farms to decipher the impact of occupational exposure on microbiome formation. The microbiota of volunteers was longitudinally profiled in a 9-months survey, in which the volunteers underwent occupational exposure during 3-month internships in swine farms. By high-throughput sequencing, we showed that occupational exposure compositionally and functionally reshaped the volunteers’ skin and nasal microbiota. The exposure in farm A reduced the microbial diversity of skin and nasal microbiota, whereas the microbiota of skin and nose increased after exposure in farm B. The exposure in different farms resulted in compositionally different microbial patterns, as the abundance of Actinobacteria sharply increased at expense of Firmicutes after exposure in farm A, yet Proteobacteria became the most predominant in the volunteers in farm B. The remodeled microbiota composition due to exposure in farm A appeared to stall and persist, whereas the microbiota of volunteers in farm B showed better resilience to revert to the pre-exposure state within 9 months after the exposure. Several metabolic pathways, for example, the styrene, aminobenzoate, and N-glycan biosynthesis, were significantly altered through our PICRUSt analysis, and notably, the function of beta-lactam resistance was predicted to enrich after exposure in farm A yet decrease in farm B. We proposed that the differently modified microbiota patterns might be coordinated by microbial and non-microbial factors in different swine farms, which were always environment-specific. This study highlights the active role of occupational exposure in defining the skin and nasal microbiota and sheds light on the dynamics of microbial patterns in response to environmental conversion

Major Miocene geological events in southern Tibet and eastern Asia induced by the subduction of the Ninetyeast Ridge

Cenozoic adakitic rocks in the Gangdese changed from barren continental melts to ore-forming slab melts at ~ 23 Ma. The distribution and chemical characteristics of the ore-forming adakites point to an association with the Ninetyeast Ridge. The subduction of the thick, rigid Ninetyeast Ridge changed the geometry and rheology of the eastern Tibetan Plateau lithosphere and asthenosphere, restrained the eastward escape of asthenospheric mantle as well as continental fragments, and promoted the uplift and building of the Tibetan Plateau, which consequently changed the tectonic and climatic regimes in eastern Asia.This study was supported by NSFC 91328204 to W.D.S. and Strategic Priority Research Program (B) of the Chinese Academy of Sciences (XDB18020102) to W.D.S. and X.L.S

An unexpected catalyst dominates formation and radiative forcing of regional haze

Although regional haze adversely affects human health and possibly counteracts global warming from increasing levels of greenhouse gases, the formation and radiative forcing of regional haze on climate remain uncertain. By combining field measurements, laboratory experiments, and model simulations, we show a remarkable role of black carbon (BC) particles in driving the formation and trend of regional haze. Our analysis of long-term measurements in China indicates declined frequency of heavy haze events along with significantly reduced SO₂, but negligibly alleviated haze severity. Also, no improving trend exists for moderate haze events. Our complementary laboratory experiments demonstrate that SO₂ oxidation is efficiently catalyzed on BC particles in the presence of NO₂ and NH₃, even at low SO₂ and intermediate relative humidity levels. Inclusion of the BC reaction accounts for about 90–100% and 30–50% of the sulfate production during moderate and heavy haze events, respectively. Calculations using a radiative transfer model and accounting for the sulfate formation on BC yield an invariant radiative forcing of nearly zero W m⁻² on the top of the atmosphere throughout haze development, indicating small net climatic cooling/warming but large surface cooling, atmospheric heating, and air stagnation. This BC catalytic chemistry facilitates haze development and explains the observed trends of regional haze in China. Our results imply that reduction of SO₂ alone is insufficient in mitigating haze occurrence and highlight the necessity of accurate representation of the BC chemical and radiative properties in predicting the formation and assessing the impacts of regional haze

Celecoxib ameliorates diabetic sarcopenia by inhibiting inflammation, stress response, mitochondrial dysfunction, and subsequent activation of the protein degradation systems

Aim: Diabetic sarcopenia leads to disability and seriously affects the quality of life. Currently, there are no effective therapeutic strategies for diabetic sarcopenia. Our previous studies have shown that inflammation plays a critical role in skeletal muscle atrophy. Interestingly, the connection between chronic inflammation and diabetic complications has been revealed. However, the effects of non-steroidal anti-inflammatory drug celecoxib on diabetic sarcopenia remains unclear.Materials and Methods: The streptozotocin (streptozotocin)-induced diabetic sarcopenia model was established. Rotarod test and grip strength test were used to assess skeletal muscle function. Hematoxylin and eosin and immunofluorescence staining were performed to evaluate inflammatory infiltration and the morphology of motor endplates in skeletal muscles. Succinate dehydrogenase (SDH) staining was used to determine the number of succinate dehydrogenase-positive muscle fibers. Dihydroethidium staining was performed to assess the levels of reactive oxygen species (ROS). Western blot was used to measure the levels of proteins involved in inflammation, oxidative stress, endoplasmic reticulum stress, ubiquitination, and autophagic-lysosomal pathway. Transmission electron microscopy was used to evaluate mitophagy.Results: Celecoxib significantly ameliorated skeletal muscle atrophy, improving skeletal muscle function and preserving motor endplates in diabetic mice. Celecoxib also decreased infiltration of inflammatory cell, reduced the levels of IL-6 and TNF-α, and suppressed the activation of NF-κB, Stat3, and NLRP3 inflammasome pathways in diabetic skeletal muscles. Celecoxib decreased reactive oxygen species levels, downregulated the levels of Nox2 and Nox4, upregulated the levels of GPX1 and Nrf2, and further suppressed endoplasmic reticulum stress by inhibiting the activation of the Perk-EIF-2α-ATF4-Chop in diabetic skeletal muscles. Celecoxib also inhibited the levels of Foxo3a, Fbx32 and MuRF1 in the ubiquitin-proteasome system, as well as the levels of BNIP3, Beclin1, ATG7, and LC3Ⅱ in the autophagic-lysosomal system, and celecoxib protected mitochondria and promoted mitochondrial biogenesis by elevating the levels of SIRT1 and PGC1-α, increased the number of SDH-positive fibers in diabetic skeletal muscles.Conclusion: Celecoxib improved diabetic sarcopenia by inhibiting inflammation, oxidative stress, endoplasmic reticulum stress, and protecting mitochondria, and subsequently suppressing proteolytic systems. Our study provides evidences for the molecular mechanism and treatment of diabetic sarcopenia, and broaden the way for the new use of celecoxib in diabetic sarcopenia