Existence Result to Boundary Value Problem for Fractional Differential Equations with Integral Boundary Conditions

Abstract: By the means of the Green's function, the boundary value problem of fractional differential equation can be reduced to the equivalent integral equation. Recently, this method is used successfully to discuss the existence of the solution to boundary value problem of nonlinear fractional differential equation. By applying Carathéodory conditions and continuous condition on the nonlinear terms f , we obtain an existence results for solution. Our analysis relies on the concept of measures of noncompactness, the Mönch ′ s fixed point theorem and the Schaefer's fixed point theorem. Example is provided to illustrate the theory

Transient receptor potential channel 1 deficiency impairs host defense and proinflammatory responses to bacterial infection by regulating protein kinase Cα signaling

Transient receptor potential channel 1 (TRPC1) is a nonselective cation channel that is required for Ca2+ homeostasis necessary for cellular functions. However, whether TRPC1 is involved in infectious disease remains unknown. Here, we report a novel function for TRPC1 in host defense against Gram-negative bacteria. TRPC1-/- mice exhibited decreased survival, severe lung injury, and systemic bacterial dissemination upon infection. Furthermore, silencing of TRPC1 showed decreased Ca2+ entry, reduced proinflammatory cytokines, and lowered bacterial clearance. Importantly, TRPC1 functioned as an endogenous Ca2+ entry channel critical for proinflammatory cytokine production in both alveolar macrophages and epithelial cells. We further identified that bacterium-mediated activation of TRPC1 was dependent on Toll-like receptor 4 (TLR4), which induced endoplasmic reticulum (ER) store depletion. After activation of phospholipase Cγ (PLC-γ), TRPC1 mediated Ca2+ entry and triggered protein kinase Cα (PKC-α) activity to facilitate nuclear translocation of NF-kB/Jun N-terminal protein kinase (JNK) and augment the proinflammatory response, leading to tissue damage and eventually mortality. These findings reveal that TRPC1 is required for host defense against bacterial infections through the TLR4-TRPC1-PKCγ signaling circuit.Fil: Zhou, Xikun. University Of North Dakota; Estados Unidos. West China Hospital Of Sichuan University; ChinaFil: Ye, Yan. University Of North Dakota; Estados UnidosFil: Sun, Yuyang. University Of North Dakota; Estados UnidosFil: Li, Xuefeng. West China Hospital Of Sichuan University; China. University Of North Dakota; Estados UnidosFil: Wang, Wenxue. University Of North Dakota; Estados UnidosFil: Privratsky, Breanna. University Of North Dakota; Estados UnidosFil: Tan, Shirui. University Of North Dakota; Estados UnidosFil: Zhou, Zongguang. West China Hospital Of Sichuan University; ChinaFil: Huang, Canhua. West China Hospital Of Sichuan University; ChinaFil: Wei, Yu-Quan. West China Hospital Of Sichuan University; ChinaFil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Institute Of Environmental Health Sciences; Estados UnidosFil: Singh, Brij B.. University Of North Dakota; Estados UnidosFil: Wu, Min. University Of North Dakota; Estados Unido

Rice Xa21 primed genes and pathways that are critical for combating bacterial blight infection

Rice bacterial blight (BB) is a devastating rice disease. The Xa21 gene confers a broad and persistent resistance against BB. We introduced Xa21 into Oryza sativa L ssp indica (rice 9311), through multi-generation backcrossing, and generated a nearly isogenic, blight-resistant 9311/Xa21 rice. Using next-generation sequencing, we profiled the transcriptomes of both varieties before and within four days after infection of bacterium Xanthomonas oryzae pv. oryzae. The identified differentially expressed (DE) genes and signaling pathways revealed insights into the functions of Xa21. Surprisingly, before infection 1,889 genes on 135 of the 316 signaling pathways were DE between the 9311/Xa21 and 9311 plants. These Xa21-mediated basal pathways included mainly those related to the basic material and energy metabolisms and many related to phytohormones such as cytokinin, suggesting that Xa21 triggered redistribution of energy, phytohormones and resources among essential cellular activities before invasion. Counter-intuitively, after infection, the DE genes between the two plants were only one third of that before the infection; other than a few stress-related pathways, the affected pathways after infection constituted a small subset of the Xa21-mediated basal pathways. These results suggested that Xa21 primed critically important genes and signaling pathways, enhancing its resistance against bacterial infection

Design of Wide-Spectrum Inhibitors Targeting Coronavirus Main Proteases

The genus Coronavirus contains about 25 species of coronaviruses (CoVs), which are important pathogens causing highly prevalent diseases and often severe or fatal in humans and animals. No licensed specific drugs are available to prevent their infection. Different host receptors for cellular entry, poorly conserved structural proteins (antigens), and the high mutation and recombination rates of CoVs pose a significant problem in the development of wide-spectrum anti-CoV drugs and vaccines. CoV main proteases (M(pro)s), which are key enzymes in viral gene expression and replication, were revealed to share a highly conservative substrate-recognition pocket by comparison of four crystal structures and a homology model representing all three genetic clusters of the genus Coronavirus. This conclusion was further supported by enzyme activity assays. Mechanism-based irreversible inhibitors were designed, based on this conserved structural region, and a uniform inhibition mechanism was elucidated from the structures of M(pro)-inhibitor complexes from severe acute respiratory syndrome-CoV and porcine transmissible gastroenteritis virus. A structure-assisted optimization program has yielded compounds with fast in vitro inactivation of multiple CoV M(pro)s, potent antiviral activity, and extremely low cellular toxicity in cell-based assays. Further modification could rapidly lead to the discovery of a single agent with clinical potential against existing and possible future emerging CoV-related diseases

Effects of bisphenol A exposure at different circadian time on hepatic lipid metabolism in mice

BackgroundLipid metabolism in liver shows circadian-dependent profiles. The hepatotoxicity of environmental chemicals is dependent on circadian time. ObjectiveTo observe the effects of bisphenol A (BPA) exposure at different zeitgeber time (ZT) on hepatic and blood lipid metabolism and decipher the underlying mechanisms related to circadian rhythm in mice. MethodsThirty-five female C57BL/6J mice were sacrificed every 4 h in a light-dark cycle (12 h/12 h). The liver tissues were collected to describe the circadian profiles of hepatic Rev-erba, Bmal1, Clock, Srebp1c, and Chrebp mRNA expression levels within 24 h. Thirty female mice were divided into 6 groups by the timing (ZT3 represents the 3 h after light on, ZT15 represents the 3 h after light off) and dose (50 or 500 μg·kg−1·d−1) of BPA exposure to observe hepatotoxicity. Mice were gavaged with designed doses of BPA once per day for 4 weeks. Mice were maintained with ad libitum access to food and water and measured body weight weekly. After the experiment, mice were euthanatized and liver tissues were separated to determine the biochemical indicators of lipid metabolism and lipid metabolism- and circadian-related gene mRNA expressions. ResultsHepatic Rev-erba, Bmal1, Clock, Srebp1c, and Chrebp mRNA expression levels were rhythmic during a 24 h period in mice. At ZT3 and ZT15, BPA did not alter body weight, plasma glucose, plasma total cholesterol, plasma low density lipoprotein cholesterol, and plasma triglycerides (P>0.05). The plasma high density lipoprotein cholesterol decreased in the 50 μg·kg−1·d−1 BPA group at ZT3 by 14.56% compared with the control group (P<0.05). The liver triglycerides increased in the 50 μg·kg−1·d−1 BPA group at ZT15 by 115.20% compared with the control group (P<0.05). BPA decreased Srebp1c mRNA expression level when dosing at ZT3 and increased Chrebp, Srebp1c, and Acc1 mRNA expression levels when dosing at ZT15 compared with the control group (P<0.05). BPA increased Bmal1 mRNA expression level and decreased Rev-erbα mRNA expression level at ZT3 exposure and decreased Bmal1 and increased Rev-erbα mRNA expression level at ZT15 exposure (P<0.05). ConclusionBPA exposure at light or dark period has different effects on hepatic lipid metabolism in mice. Hepatic lipid deposit appears when BPA is dosed at dark period. Rev-erbα-Bmal1 regulation circuits and the subsequent upregulation of Srebp1c and Chrebp and the target gene Acc1 may be involved

Gap Junction Mediated Intercellular Metabolite Transfer in the Cochlea Is Compromised in Connexin30 Null Mice

Connexin26 (Cx26) and connexin30 (Cx30) are two major protein subunits that co-assemble to form gap junctions (GJs) in the cochlea. Mutations in either one of them are the major cause of non-syndromic prelingual deafness in humans. Because the mechanisms of cochlear pathogenesis caused by Cx mutations are unclear, we investigated effects of Cx30 null mutation on GJ-mediated ionic and metabolic coupling in the cochlea of mice. A novel flattened cochlear preparation was used to directly assess intercellular coupling in the sensory epithelium of the cochlea. Double-electrode patch clamp recordings revealed that the absence of Cx30 did not significantly change GJ conductance among the cochlear supporting cells. The preserved electrical coupling is consistent with immunolabeling data showing extensive Cx26 GJs in the cochlea of the mutant mice. In contrast, dye diffusion assays showed that the rate and extent of intercellular transfer of multiple fluorescent dyes (including a non-metabolizable D-glucose analogue, 2-NBDG) among cochlear supporting cells were severely reduced in Cx30 null mice. Since the sensory epithelium in the cochlea is an avascular organ, GJ-facilitated intercellular transfer of nutrient and signaling molecules may play essential roles in cellular homeostasis. To test this possibility, NBDG was used as a tracer to study the contribution of GJs in transporting glucose into the cochlear sensory epithelium when delivered systemically. NBDG uptake in cochlear supporting cells was significantly reduced in Cx30 null mice. The decrease was also observed with GJ blockers or glucose competition, supporting the specificity of our tests. These data indicate that GJs facilitate efficient uptake of glucose in the supporting cells. This study provides the first direct experimental evidence showing that the transfer of metabolically-important molecules in cochlear supporting cells is dependent on the normal function of GJs, thereby suggesting a novel pathogenesis process in the cochlea for Cx-mutation-linked deafness

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Two ultraviolet radiation datasets that cover China

Ultraviolet (UV) radiation has significant effects on ecosystems, environments, and human health, as well as atmospheric processes and climate change. Two ultraviolet radiation datasets are described in this paper. One contains hourly observations of UV radiation measured at 40 Chinese Ecosystem Research Network stations from 2005 to 2015. CUV3 broadband radiometers were used to observe the UV radiation, with an accuracy of 5%, which meets the World Meteorology Organization's measurement standards. The extremum method was used to control the quality of the measured datasets. The other dataset contains daily cumulative UV radiation estimates that were calculated using an all-sky estimation model combined with a hybrid model. The reconstructed daily UV radiation data span from 1961 to 2014. The mean absolute bias error and root-mean-square error are smaller than 30% at most stations, and most of the mean bias error values are negative, which indicates underestimation of the UV radiation intensity. These datasets can improve our basic knowledge of the spatial and temporal variations in UV radiation. Additionally, these datasets can be used in studies of potential ozone formation and atmospheric oxidation, as well as simulations of ecological processes