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A reasonable calculation of railway capacity is very important for research. With the rapid development of high-speed railways, more and more differences between traditional and modern railways have emerged in the transportation organization and capacity calculation methods. In this article, the calculation methods used under different conditions with different train types are studied based on the train deduction method. Train deduction is a method that calculates the number of trains that cannot pass through the line when other trains change their stop plan or operation speed based on the coefficient of deduction method, which is widely used in China. Then, optimized models for trains with the same-speed and different-speeds are built to determine the maximum number of trains. These models are built based on the constraints of passenger service quality and overtaking times. In addition, the models are solved based on a train operation plan. Hence, the capacity calculated by these methods is more reasonable for the actual condition. Finally, an actual case of Beijing–Shanghai high-speed railway is implemented and tested with the model. The optimal capacity scheme is simulated and analysed, and the result agreed well with the railway transport enterprise. [ABSTRACT FROM AUTHOR]

The article highlights a study on Drosophila HisC mutant embryos harboring a deletion of all canonical histone genes, in which nucleosome assembly relies on parental histones from cell cycle 14 onward. It discusses that the genomic positions of modified parental histone H2A, H2B, and H3 are largely restored during DNA replication; and concludes that parental histones are recycled to preserve the epigenetic landscape during DNA replication in vivo.

The lytic replication of Kaposi 17;s sarcoma-associated herpesvirus (KSHV) requires sustained extracellular signal-regulated kinase (ERK)-p90 ribosomal S6 kinase (RSK) activation, which is induced by an immediate early (IE) gene-encoded tegument protein called ORF45, to promote the late transcription and translation of viral lytic genes. An ORF45-null or single-point F66A mutation in ORF45 abolishes ORF45-RSK interaction and sustained ERK-RSK activation during lytic reactivation and subsequently results in a significant decrease in late lytic gene expression and virion production, indicating that ORF45-mediated RSK activation plays a critical role in KSHV lytic replication. Here, we demonstrate that a short ORF45-derived peptide in the RSK-binding region is sufficient for disrupting ORF45-RSK interaction, consequently suppressing lytic gene expression and virion production. We designed a nontoxic cell-permeable peptide derived from ORF45, TAT-10F10, which is composed of the ORF45 56 to 76 amino acid (aa) region and the HIV Tat protein transduction domain, and this peptide markedly inhibits KSHV lytic replication in iSLK.219 and BCBL1 cells. Importantly, this peptide enhances the inhibitory effect of rapamycin on KSHV-infected cells and decreases spontaneous and hypoxia-induced lytic replication in KSHV-positive lymphoma cells. These findings suggest that a small peptide that disrupts ORF45-RSK interaction might be a promising agent for controlling KSHV lytic infection and pathogenesis. [ABSTRACT FROM AUTHOR]

The plant transmembrane receptor kinase FLAGELLIN SENSING 2 (FLS2) is crucial for innate immunity. Although previous studies have reported FLS2-mediated signal transduction and endocytosis via the clathrin-mediated pathway, whether additional endocytic pathways affect FLS2-mediated defense responses remains unclear. Here, we show that the Arabidopsis thaliana sterol-deficient mutant steroid methyltransferase 1 displays defects in immune responses induced by the flagellin-derived peptide flg22. Variable-angle total internal reflection fluorescence microscopy (VA-TIRFM) coupled with single-particle tracking showed that the spatiotemporal dynamics of FLS2-GFP changed on a millisecond time scale and that the FLS2-GFP dwell time at the plasma membrane increased in cells treated with a sterol-extracting reagent when compared with untreated counterparts. We further demonstrate that flg22-induced FLS2 clustering and endocytosis involves the sterol-associated endocytic pathway, which is distinct from the clathrin-mediated pathway. Moreover, flg22 enhanced the colocalization of FLS2-GFP with the membrane microdomain marker Flot 1-mCherry and FLS2 endocytosis via the sterol-associated pathway. This indicates that plants may respond to pathogen attacks by regulating two different endocytic pathways. Taken together, our results suggest the key role of sterol homeostasis in flg22-induced plant defense responses. [ABSTRACT FROM AUTHOR]

Hypodematium confertivillosum J.X.Li, F.Q.Zhou & X.J.Li, sp. nov., a new species of Hypodematium from Shandong, China, is described and illustrated. It is similar to H. crenatum (Forssk.) Kuhn & Decken and H. glanduloso-pilosum (Tagawa) Ohwi, but differs greatly from them by its abaxial fronds sparsely covered with rod-shaped glandular hairs, its adaxial fronds without rod-shaped glandular hairs and spore reniform, with verrucate processes, surface with distinct finely lamellar rugae ornamentation. The description, photographs and a key to H. confertivillosum as well as their notes are provided. [ABSTRACT FROM AUTHOR]

Among end-stage renal disease patients maintained by hemodialysis, anemia has been managed primarily through erythropoiesis-stimulating agents (ESAs) and intravenous (IV) iron. Following concerns about the cardiovascular (CV) safety of ESAs and changes in the reimbursement policies in Medicare's ESRD program, the use of IV iron has increased. IV iron supplementation promotes hemoglobin production and reduces ESA requirements, yet there exists relatively little evidence on the long-term safety of iron supplementation in hemodialysis 'patients. Labile iron can induce oxidative stress and is also essential in bacterial growth, leading to concerns about IV iron use and risk of CV events and infections in hemodialysis patients. Existing randomized controlled trials provide little evidence about safety due to insufficient power and short follow-up; recent observational studies have been inconsistent, but some have associated iron exposure with increased risk of infections and CV events. Given the widespread use and potential safety concerns related to IV iron, well-designed large prospective studies are needed to assess to identify optimal strategies for iron administration that maximize its benefits while avoiding potential risks. [ABSTRACT FROM AUTHOR]

The developmental plasticity of plants relies on the remarkable ability of the meristems to integrate nutrient and energy availability with environmental signals.Meristems in root and shoot apexes share highly similar molecular players but are spatially separated by soil. Whether and how these two meristematic tissues have differential activation requirements for local nutrient, hormone, and environmental cues (e.g., light) remain enigmatic in photosynthetic plants. Here, we report that the activation of root and shoot apexes relies on distinct glucose and light signals. Glucose energy signaling is sufficient to activate target of rapamycin (TOR) kinase in root apexes. In contrast, both the glucose and light signals are required for TOR activation in shoot apexes. Strikingly, exogenously applied auxin is able to replace light to activate TOR in shoot apexes and promote true leaf development. A relatively low concentration of auxin in the shoot and high concentration of auxin in the root might be responsible for this distinctive light requirement in root and shoot apexes, because light is required to promote auxin biosynthesis in the shoot. Furthermore, we reveal that the small GTPase Rho-related protein 2 (ROP2) transduces light-auxin signal to activate TOR by direct interaction, which, in turn, promotes transcription factors E2Fa,b for activating cell cycle genes in shoot apexes. Consistently, constitutively activated ROP2 plants stimulate TOR in the shoot apex and cause true leaf development even without light. Together, our findings establish a pivotal hub role of TOR signaling in integrating different environmental signals to regulate distinct developmental transition and growth in the shoot and root. [ABSTRACT FROM AUTHOR]

A useful method for eliminating the detrimental effect of laser frequency instability on Brillouin signals by employing the self-heterodyne detection of Rayleigh and Brillouin scattering is presented. From the analysis of Brillouin scattering spectra from fibers with different lengths measured by heterodyne detection, the maximum usable pulse width immune to laser frequency instability is obtained to be about 4 µs in a self-heterodyne detection Brillouin optical time domain reflectometer (BOTDR) system using a broad-band laser with low frequency stability. Applying the self-heterodyne detection of Rayleigh and Brillouin scattering in BOTDR system, we successfully demonstrate that the detrimental effect of laser frequency instability on Brillouin signals can be eliminated effectively. Employing the broad-band laser modulated by a 130-ns wide pulse driven electro-optic modulator, the observed maximum errors in temperatures measured by the local heterodyne and self-heterodyne detection BOTDR systems are 7.9 °C and 1.2 °C, respectively. [ABSTRACT FROM AUTHOR]

The rapid development of Unmanned Aerial Vehicle (UAV) remote sensing conforms to the increasing demand for the low-altitude very high resolution (VHR) image data. However, high processing speed of massive UAV data has become an indispensable prerequisite for its applications in various industry sectors. In this paper, we developed an effective and efficient seam elimination approach for UAV images based on Wallis dodging and Gaussian distance weight enhancement (WD-GDWE). The method encompasses two major steps: first, Wallis dodging was introduced to adjust the difference of brightness between the two matched images, and the parameters in the algorithm were derived in this study. Second, a Gaussian distance weight distribution method was proposed to fuse the two matched images in the overlap region based on the theory of the First Law of Geography, which can share the partial dislocation in the seam to the whole overlap region with an effect of smooth transition. This method was validated at a study site located in Hanwang (Sichuan, China) which was a seriously damaged area in the 12 May 2008 enchuan Earthquake. Then, a performance comparison between WD-GDWE and the other five classical seam elimination algorithms in the aspect of efficiency and effectiveness was conducted. Results showed that WD-GDWE is not only efficient, but also has a satisfactory effectiveness. This method is promising in advancing the applications in UAV industry especially in emergency situations. [ABSTRACT FROM AUTHOR]

Ustilaginoidea virens is the causal agent of a serious disease of rice. To reveal the relationship between germination and the 3'-5'-cyclic adenosine monophosphate (cAMP) content from the dormant (black or green-black) and non-dormant (yellow) chlamydospore in Ustiloginoidea virens,this study adopts ultrasonic-bath method and high-performance liquid chromatography (HPLC) method, for extraction cAMP content of the different color chlamydospore. The results demonstrated that, as for the freshly chlamydospores collected from the false smut balls during their germination, cAMP content of yellow chlamydospore appeared a slight growth during 0-12 h, and showed a rapid declining as the germination time extended (12-48 h) . Above all, in yellow chlamydospores, the germination rate and the content of cAMP presented a very notably negative correlation (|r|=0.861 9>r0.01=0.834), but the correlation between germination rate and content of cAMP was not obvious in black chlamydospores. The germination rate and the content of cAMP presented a notably positive correlation under different storage period (0, 2, 4, 6, 8, 10 months) of the two color chlamydospores (the yellow of chlamydospore: |r| = 0.785 1 > r0.05 = 0.707; the black of chlamy-dospore: |r| = 0.957 9 > r0.05 = 0.707). [ABSTRACT FROM AUTHOR]

Kaposi's sarcoma-associated herpesvirus (KSHV) encodes multiple viral proteins that activate extracellular signal-regulated kinase (ERK)-mitogen-activated protein kinase (MAPK) cascades. One of these viral proteins, ORF45, mediates sustained ERKp90 ribosomal S6 kinase (RSK) activation during KSHV lytic replication and facilitates viral translation through the phosphorylation of a eukaryotic translation initiation factor, eIF4B. The importance of ERK-RSK activation for KSHV viral transcription has been shown; however, which transcription factor senses the sustained MAPK signaling and leads to viral transcription remains poorly understood. Here we show that the presence of ORF45 leads to the prolonged accumulation of c-Fos during the late stage of KSHV lytic replication through ERK-RSK-dependent phosphorylation and stabilization and that the depletion of c-Fos disrupts viral lytic transcription. Genome-wide screening revealed that c-Fos directly binds to multiple viral gene promoters and enhances viral transcription. Mutation of the ERK-RSK phosphorylation sites of c-Fos restrains KSHV lytic gene expression and virion production. These results indicate that the prolonged accumulation of c-Fos promotes the progression of viral transcription from early to late stages and accelerates viral lytic replication upon sustained ORF45-ERK-RSK activation during the KSHV lytic life cycle. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small noncoding regulatory RNAs that play key roles in the process of plant development. To date, extensive studies of miRNAs have been performed in a few model plants, but few efforts have focused on small RNAs (sRNAs) in conifers because of the lack of reference sequences for their enormous genomes. In this study, Solexa sequencing of three sRNA libraries obtained from dormant, reactivating, and active vascular cambium in Chinese fir (Cunninghamia lanceolata) using tangential cryosectioning identified 20 known miRNA families and 18 novel potential miRNAs, of which nine novel miRNA precursors were validated by RT-PCR and sequencing. More than half of these novel miRNAs displayed stage-specific expression patterns in the vascular cambium. Furthermore, analysing the 103 miRNAs and their predicted targets indicated that about 70% appeared to negatively regulate their targets, of which two target genes involved in the regulation of cambial cell division were validated via RNA ligasemediated rapid amplification of 5'-cDNA ends (RLM 5'-RACE) and transient co-expression in Nicotiana benthamiana leaves. Interestingly, miRNA156 and miRNA172 may regulate the phase transition in vascular cambium from dormancy to active growth. These results provide new insights into the important regulatory functions of miRNAs in vascular cambium development and wood formation in conifers. [ABSTRACT FROM AUTHOR]

The thermal expansion and phase transition of unpoled and poled [0 0 1]-oriented 0.69Pb(Mg1/3Nb2/3)O3-0.31PbTiO3 crystals are investigated using thermomechanical analysis, domain evolution, and dielectric measurement. Results of thermomechanical analysis show that the unpoled crystal exhibits negative thermal expansion at a temperature range from 30 °C to 120 °C, and the lattice parameter c of the tetragonal (T) phase is larger than those of the rhombohedral (R) and cubic (C) phases, i.e., cT > cR and cT > cC. Two additional structural modifications near 50 °C and 125 °C are detected in the unpoled crystal. Compared with that of the poled crystal, the T → C phase transition temperature of the unpoled crystal is relatively higher. An increase in temperature causes the unpoled crystal to undergo R → T → C phase transition, whereas R → M → T → C phase transition sequences are observed in the poled crystal. The phase transition behaviors are further verified by domain evolution and dielectric measurement. The significant differences between poled and unpoled crystals are attributed to the differences in their domain structures. [ABSTRACT FROM AUTHOR]

This aim of this study was to investigate whether progesterone (PROG) alleviates the neuronal apoptosis in neonatal rats with hypoxic-ischemic (HI) brain damage through the phosphatidylinositol 3-kinase (PI3K)/Akt/glycogen synthase kinase-3β (GSK-3β) signaling pathway. A total of 96 newborn Wistar rats aged 7 days were randomly divided into four groups: sham surgery, HI, drug prevention (PROG) and Akt inhibitor groups. HI animal models were established by a conventional method. All animals were sacrificed 24 h after hypoxia. Immunohistochemistry was used to detect the distribution and expression of phosphorylated Akt (p-Akt) and the GSK-3β proteins in the brain, and western blot analysis was used to determine the p-Akt and GSK-3β protein contents. An enzyme-linked immunosorbent assay was also used to determine the GSK-3β content of the brain tissue, and flow cytometry was used to evaluate the apoptosis rate of neural cells. The expression of p-Akt protein was reduced in the brain tissues of the HI group, whereas GSK-3β expression was increased. In addition, the GSK-3β content of the brain and the neuronal apoptosis rate were significantly increased. PROG pre-treatment increased p-Akt expression, decreased GSK-3β expression and GSK-3β content, and also reduced neuronal apoptosis. Following administration of the Akt inhibitor wortmannin, p-Akt expression decreased, GSK-3β expression increased, and the GSK-3β content and neuronal apoptosis rate significantly increased (P<0-05). In conclusion, PROG activates the PI3K/Akt/GSK-3β pathway to promote Akt activation, enhance p-Akt expression and inhibit GSK-3β expression, thereby inhibiting neuronal apoptosis, alleviating HI brain injury and inducing a cerebroprotective effect. [ABSTRACT FROM AUTHOR]

Rill erosion accounts for approximately 70% of the total erosion of upland areas in China's Loess Plateau. A laboratory rainfall experiment with deionized water was conducted to examine the process of rill evolution and the relationship between runoff, rill evolution, and erosion rates for clay loam and loess soils given a fixed slope gradient (10°) and two rainfall intensities (1.5 and 2.0 mm min-1). The results show that rills evolved from a series of parallel drop-pit chains along the down-slope direction. Clay loam soil produced rills under a rainfall intensity of 1.5 mm min-1, and loess soil produced rills only under higher rainfall intensity. The temporal change in sediment concentration and erosion rate shows good consistency with the emergence of drop pits and rills. An increase in rainfall intensity had little effect on the sediment concentration and erosion rate for clay loam soil, whereas for loess soil, both increased rapidly and exceeded those of clay loam soil, with the emergence of a rill when the rainfall intensity was higher. Rills have a much greater effect on sediment concentration and erosion rate for loess soil than for clay loam soil. This study indicates that soil texture has a major impact on rill formation; clay loam soil is more subject to rill formation, but the rills formed are generally small and do not substantially increase soil loss. in contrast, the well-developed rills in silt loam soil can result in intensive soil loss, though rills occur infrequently. Basic understanding of these results, causes, and quantification are essential for the prediction and evaluation of soil loss. [ABSTRACT FROM AUTHOR]

Progesterone (PROG) has been shown to exhibit a protective function against hypoxic-ischemic brain damage. The aim of the present study was to study the effects of PROG in a neonatal rat model of hypoxic-ischemic brain injury. A total of 30 Wistar rats, aged 7 days, were randomly divided into three groups: Sham, model and PROG. The rats in the model and PROG groups underwent a left common carotid artery ligation and were placed in a sealed container at 37°C with 8% O2 and 92% N2 gas mixtures for 2.5 h to establish animal models of hypoxic-ischemic encephalopathy. The rats in the PROG group were intraperitoneally treated with 8 mg/kg PROG solution 30 min prior to the induction of hypoxia-ischemia. All animals were sacrificed after 24 h and neuronal changes were observed with electron microscopy to investigate the hypoxic-ischemic brain damage. The protein and mRNA expression levels of tumor necrosis factor-α (TNF-α) and nuclear factor-κB (NF-κB) in the hippocampus were detected by immunohistochemistry and quantitative polymerase chain reaction, respectively. The results revealed that the neuronal structures in the sham group were normal. The neuronal structures in the model group exhibited cavitation changes, but these were reduced following PROG administration. The protein and mRNA expression levels of TNF-α and NF-κB in the hippocampal neurons were increased in the model group, and pretreatment with 8 mg/kg PROG was shown to reduce the expression levels of these inflammatory mediators. Therefore, PROG was shown to exert an important protective function in hypoxic-ischemic brain injury by inhibiting the cascade of inflammatory injury induced by TNF-α and NF-κB. [ABSTRACT FROM AUTHOR]

Background Leukemia is the most common malignant proliferative disease in children. Our previous study found that miR-99a was up-regulated in pediatric primary AML using microRNA expression profiles. Up to date, although there is a certain number of reports on microRNA expression features and functions in pediatric acute myeloid leukemia (AML) and chronic myeloid leukemia (CML), the expression and function of miR-99a in these diseases remain to be investigated. Methods qRT-PCR was performed to measure the expression level of miR-99a in 88 samples including 68 pediatric acute myeloid leukemia patients, 8 chronic myeloid leukemia patients and 12 pediatric controls. MTT assay, apoptosis assay, dual-luciferase reporter transfection assay and western blot analysis were used to investigate the function of miR-99a. Results MiR-99a was highly expressed in pediatric-onset AML (M1-M5) and CML, while significantly lowly expressed during complete remission of these diseases. MTT assay indicated that the proliferations of K562 and HL60 cells were significantly promoted by miR- 99a, and apoptosis assessment by Annexin V/propidium iodide staining demonstrated that the apoptosis of these cells was inhibited by miR-99a. Additionally, dual-luciferase reporter transfection assay and western blot analysis indicated that miR-99a may target CTDSPL and TRIB2, which are two tumor suppressor genes. Conclusions This study revealed that miR-99a may play a potential oncogenic role in pediatric myeloid leukemia including AML and CML via regulating tumor suppressors CTDSPL and TRIB2, suggesting that these two leukemias might share some common biological pathways involved in the generation and development of disease and miR-99a could be a common therapeutic target for myeloid leukemias treatment. [ABSTRACT FROM AUTHOR]

B lymphocytes producing antiplatelet au-toantibodies play a major role in autoim-mune thrombocytopenia (ITP). However, certain B cells, including the human CD19+CD24hiCD38hi subpopulation, pos-sess regulatory functions mediated partly by IL-10. In a cohort of chronic ITP patients with low platelet counts who consisted of patients off treatment, we found a lower frequency of CD19+CD24hiCD38hi in the peripheral compartment of nonsple-nectomized patients (P = .03). IL-10 expression after activation was decreased in all ITP circulating CD19+ subpopula-tions (P < .03), and inhibition of mono-cyte TNF-α expression by activated B cells was reduced in patients with plate-let numbers of < 50 x 109 cells/L (P=.001), indicating that regulatory B cells of patients with ITP are functionally impaired in their ability to dampen monocyte activation. Interestingly, In non-splenectomized patients whose platelet counts were elevated after treatment with thrombopoietic agents, the frequency of CD19+CD24hiCD38hi B cells was increased compared with those before treatment (P=.02). Altogether, these data indicate a compromised regulatory B-cell com-partment as an additional defect in immune regulation in patients with chronic ITP that may be restored in responders to thrombopoietic treatment. [ABSTRACT FROM AUTHOR]

Purpose: the purpose of this study was to develop and test a method for measuring pressure in the upper urinary tract during ureteroscopic operations and to evaluate its efficacy and clinical significance. Methods: A total of 44 patients, each with a ureteral calculus in the proximal ureteral segment, were enrolled in the study group: 21 patients with an acute and 23 with a chronic obstruction. The ureteroscope was passed forward to the upper segment of the obstructed ureter immediately after the calculus was broken and the intraluminal ureteral pressure was then transmitted along with the irrigant ow (0.9% sodium chloride). Results: the mean ureteral pressures of the acute obstruction subgroup, the chronic obstruction subgroup and the control group were 74.5 mmHg (22-180 mmHg), 32.5 mmHg (9-53 mmHg) and 10.2 mmHg (8-13 mmHg), respectively. A significant correlation was found between ureteral pressure and the following indexes: the duration of the obstruction (r=0.985), the diameter of the ureter above the calculus (r=0.878) and the depth of the hydronephrosis of the renal pelvis (r=0.862). No associations were observed between the pressure and the serum creatinine level (r=0.214) or the urinary leukocyte count (r=0.047). The intraluminal pressure correlated with the glomerular ow rate (GFR) of the affected kidney (r =0.975, P =0.001). Conclusions:This new method is non-invasive, practical and reproducible. Measuring the intraluminal pressure of the ureter can provide a valuable index to quantify the severity of the obstruction of the upper urinary tract, which is helpful for the prediction of the affected renal function prognosis. [ABSTRACT FROM AUTHOR]

Although differentiation of the isomeric Asn deamidation products (Asp and isoAsp) at the peptide level by electron capture dissociation (ECD) has been well-established, isoAsp identification at the intact protein level remains a challenging task. Here, a comprehensive top-down deamidation study is presented using the protein beta2-microglobulin (β2M) as the model system. Of the three deamidation sites identified in the aged β2M, isoAsp formation was detected at only one site by the top-down ECD analysis. The absence of diagnostic ions likely resulted from an increased number of competing fragmentation channels and a decreased likelihood of product ion separation in ECD of proteins. To overcome this difficulty, an MS3 approach was applied where a protein ion was first fragmented by collisionally activated dissociation (CAD) and the resulting product ion was isolated and further analyzed by ECD. IsoAsp formation at all three deamidation sites was successfully identified by this CAD-ECD approach. Furthermore, the abundance of the isoAsp diagnostic ion was found to increase linearly with the extent of deamidation. These results demonstrated the potential of ECD in the detection and quantitative analysis of isoAsp formation using the top-down approach. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging (MRI) is gaining increasing significance to study disease burden and progression in osteoarthritis. Bone marrow edema pattern has been identified as a typical MR finding associated with osteoarthritis. Histologically, bone marrow edema pattern is characterized by a mix of different pathologies, including bone marrow necrosis, fibrosis, microfractures, and bone remodeling as well as fibrovascular ingrowth. On MR imaging, bone marrow edema pattern is typically associated with subchondral cysts, cartilage defects, and meniscal degeneration; prevalence and size correlates with disease severity. Bone marrow edema pattern may be found in association with other abnormalities such as subchondral insufficiency fractures. Clinically the significance of bone marrow edema is controversially discussed with some studies showing evidence of associated pain. In summary, bone marrow signal abnormalities are frequent MRI signs of osteoarthritis with different histological findings, typical associated abnormalities, and also clinical significance. [ABSTRACT FROM AUTHOR]

Due to its much slower deamidalion rate compared to that of asparagine (Asn), studies on glutamine (Gin) deamidation have been scarce, especially on the differentiation of its isomeric deamidation products: α- and γ-glutamic acid (Glu). It has been shown previously that electron capture dissociation (ECD) can be used to generate diagnostic ions for the deamidalion products of Asn: aspartic acid (Asp) and isoaspartic acid (isoAsp). The current study explores the possibility of an extension of this ECD based method to the differentiation of the α- and γ-Glu residues, using three human Crystallin peptides (αA (1-11), βB2 (4-14), and γS (52-71)) and their potentially deamidated forms as model peptides. it was found that the Z∙-72 ions can be used to both identify the existence and locate the position of the γ-Glu residues. When the peptide contains a charge carrier near its N- terminus, the c+57 and c+59 ions may also be generated at the γ-Glu residue. It was unclear whether formation of these N-terminal diagnostic ions is specific to the Pro-γ-Glu sequence. Unlike the Asp containing peptides, the Glu containing peptides generally do not produce diagnostic side chain loss ions, due to the instability of the resulting radical. The presence of Glu residue(s) may be inferred from the observation of a series of zn∙-59 ions, although it was neither site specific nor without interference from the γ-Glu residues. Finally, several interference peaks exist in the ECD spectra, which highlights the importance of the use of high performance mass spectrometers for confident identification of γ-Glu residues. [ABSTRACT FROM AUTHOR]

Retroperitoneal laparoscopic ureterolithotomy is a new option to treat upper and middle ureter calculi in selected patients. However, migration of the stone and the flow of urine will influence the success. We have developed a new and practical method using a clamp proximally above the stone to fix its position and prevent urine flow. Twenty patients had undergone retroperitoneal laparoscopic ureterolithotomy using this method. A bulldog artery clamp was used as the temporary clamp and was placed at the proximal part of the ureter during the procedures of incision, intubation and suture. The average age of the patients was 42.5 years (range: 26–73) and the average stone size was 13.7 mm (range: 10–28). The average operating time was 38.2 min (range: 30–85). All target stones were successfully extracted without major complications. The average time of post-operation drain removal was 1.5 days. No case of prolonged urine leakage or ureter stricture was recorded. We conclude that using a temporary ureter clamp is a feasible and practical method to fix the stone and minimize the difficulty of retroperitoneal laparoscopic ureterolithotomy. [ABSTRACT FROM AUTHOR]

In this paper, we study the uniqueness problems on entire functions sharing one value. We improve and generalize some previous results of Zhang and Lin [11]. On the one hand, we consider the case for some more general differential polynomials [fnP(f)](k) where P(w) is a polynomial; on the other hand, we relax the nature of sharing value from CM to IM. [ABSTRACT FROM AUTHOR]

Open reading frame 45 (ORF45) of Kaposi's sarcoma-associated herpesvirus 8 (KSHV) is an immediate-early phosphorylated tegument protein and has been shown to play important roles at both early and late stages of viral infection. Homologues of ORF45 exist only in gammaherpesviruses, and their homology is limited. These homologues differ in their protein lengths and subcellular localizations. We and others have reported that KSHV ORF45 is localized predominantly in the cytoplasm, whereas its homologue in murine herpesvirus 68 is localized exclusively in the nucleus. We observed that ORF45s of rhesus rhadinovirus and herpesvirus saimiri are found exclusively in the nucleus. As a first step toward understanding the mechanism underlying the distinct intracellular distribution of KSHV ORF45, we identified the signals that control its subcellular localization. We found that KSHV ORF45 accumulated rapidly in the nucleus in the presence of leptomycin B, an inhibitor of CRM1 (exportin 1)-dependent nuclear export, suggesting that it could shuttle between the nucleus and cytoplasm. Mutational analysis revealed that KSHV ORF45 contains a CRM1-dependent, leucine-rich-like nuclear export signal and an adjacent nuclear localization signal. Replacement of the key residues with alanines in these motifs of ORF45 disrupts its shuttling between the cytoplasm and nucleus. The resulting ORF45 mutants have restricted subcellular localizations, being found exclusively either in the cytoplasm or in the nucleus. Recombinant viruses were reconstituted by introduction of these mutations into KSHV bacterial artificial chromosome BAC36. The resultant viruses have distinct phenotypes. A mutant virus in which ORF45 is restricted to the cytoplasm behaves as an ORF45-null mutant and produces 5- to 10-fold fewer progeny viruses than the wild type. In contrast, mutants in which the ORF45 protein is mostly restricted to the nucleus produce numbers of progeny viruses similar to those produced by the wild type. These data suggest that the subcellular localization signals of ORF45 have important functional roles in KSHV lytic replication. [ABSTRACT FROM AUTHOR]

Electron capture dissociation (ECD) studies of two modified amyloid β peptides (20–29 and 25–35) were performed to investigate the role of H• radicals in the ECD of peptide ions and the free-radical cascade (FRC) mechanism. 2,4,6-Trimethylpyridinium (TMP) was used as the fixed charge tag, which is postulated to both trap the originally formed radical upon electron capture and inhibit the H• generation. It was found that both the number and locations of the fixed charge groups influenced the backbone and side-chain cleavages of these peptides in ECD. In general, the frequency and extent of backbone cleavages decreased and those of side-chain cleavages increased with the addition of fixed charge tags. A singly labeled peptide with the tag group farther away from the protonated site experienced a smaller abundance decrease in backbone cleavage fragments than the one with the tag group closer to the protonated site. Despite the nonprotonated nature of all charge carriers in doubly labeled peptide ions, several c and z• ions were still observed in their ECD spectra. Thus, although H• transfer may be important for the N-Cα bond cleavage, there also exist other pathways, which would require a radical migration via H• abstraction through space or via an amide superbase mechanism. Finally, internal fragment ions were observed in the ECD of these linear peptides, indicating that the important role of the FRC in backbone cleavages is not limited to the ECD of cyclic peptides. [Copyright &y& Elsevier]

In this paper, we give a necessary condition for the existence of P 3-factor in the square of a tree. Furthermore, we show that the square of any tree on at least 6 vertices has a { P 3, P 4}-factor. As a consequence, every connected graph on at least 6 vertices has a { P 3, P 4}-factor. [ABSTRACT FROM AUTHOR]

In wheat (Triticum aestivum L), the leaves particularly flag leaves have been considered to be the key organs contributing to higher yields, whereas awns have been considered subsidiary organs. Compared with extensive investigations on the assimilation contribution of leaves, the photosynthetic characteristics of awns have not been well studied. In this study, we investigated the ultrastructure of chloroplasts, oxygen evolution, and phosphoenolpyruvate carboxylase [phosphoenolpyruvate carboxylase (PEPCase) EC 4.1.1.31)] activity in both flag leaves and awns during the ontogenesis of wheat. Transmission electron microscope observations showed initial increases in the sizes of grana and the degree of granum stacks from the florescence-emergence stage both in flag leaves and in awns, followed by the breakdown of membrane systems after the milk-development stage. The results of oxygen evolution assays revealed that in both organs, the rate of photosynthesis increased in the first few stages and then decreased, but the decrease occurred much earlier in flag leaves than in awns. A PEPCase activity assay demonstrated that the activity of PEPCase was much higher in awns than in flag leaves throughout ontogeny; the value was particularly high at the late stages of grain filling. Our results suggest that awns play a dominant role in contributing to large grains and a high grain yield in awned wheat cultivars, particularly during the grain-filling stages. [ABSTRACT FROM AUTHOR]

MYB transcription factor genes play important roles in many developmental processes and in various defence responses of plants. Two Arabidopsis R2R3-type MYB genes, AtMYB59 and AtMYB48, were found to undergo similar alternative splicing. Both genes have four distinctively spliced transcripts that encode either MYB-related proteins or R2R3-MYB proteins. An extensive BLAST search of the GenBank database resulted in finding and cloning two rice homologues, both of which were also found to share a similar alternative splicing pattern. In a semi-quantitative study, the expression of one splice variant of AtMYB59 was found to be differentially regulated in treatments with different phytohormones and stresses. GFP fusion protein analysis revealed that both of the two predicted nuclear localization signals (NLSs) in the R3 domain are required for localizing to the nucleus. Promoter–GUS analysis in transgenic plants showed that 5′-UTR is sufficient for the translation initiation of type 3 transcripts (encoding R2R3-MYB proteins), but not for type 2 transcripts (encoding MYB-related proteins). Moreover, a new type of non-canonical intron, with the same nucleotide repeats at the 5′ and 3′ splice sites, was identified. Thirty-eight Arabidopsis and rice genes were found to have this type of non-canonical intron, most of which undergo alternative splicing. These data suggest that this subgroup of transcription factor genes may be involved in multiple biological processes and may be transcriptionally regulated by alternative splicing. [ABSTRACT FROM PUBLISHER]

The nuclear-encoded factors and the photosynthetic apparatus have been studied extensively during chloroplast biogenesis. However, many questions regarding these processes remain unanswered, particularly in perennial woody plants. As a model material of woody plants, poplar not only has very significant value of research, but also possesses economic and ecological properties. This study reports the Populus trichocarpa DJ-1C (PtrDJ1C) factor, encoded by a nuclear gene, and a member of the DJ-1 superfamily. PtrDJ1C knock-out with the CRISPR/Cas9 system resulted in different albino phenotypes. Chlorophyll fluorescence and immunoblot analyses showed that the levels of photosynthetic complex proteins decreased significantly. Moreover, the transcript level of plastid-encoded RNA polymerase-dependent genes and the splicing efficiency of several introns were affected in the mutant line. Furthermore, rRNA accumulation was abnormal, leading to developmental defects in chloroplasts and affecting lignin accumulation. We concluded that the PtrDJ1C protein is essential for early chloroplast development and lignin deposition in poplar. [ABSTRACT FROM AUTHOR]

Four sect. of seed-like Fruits (including 14 species) of Subg. Sclarea of Salvia of Labiatae in China were systematically observed and researched by using both biological anatomical lens and scanning electron microscope (98 photographs were attached). Their shapes were ovoid, elliptical and fusiform and so on; the sizes were large, medium and small; the surface ultrastructures of seed-like Fruits were ranged from plain, stripes, reticulate to convex meshes and the like. The relationships among them and the position of evolution and the relationships among three Ser. of Sect. Drymosphace were discussed. According to the surface ornamentation types analysis of seed-like Fruits, their evolution was from plain, stripes, reticulate, convex meshes to reticulate and convex meshes, and both reticulate and convex meshes appeared on dorsal and ventral surfaces of seed-like Fruits of one species at the same time. The plain was an original type; the stripes, reticulate and convex meshes were intermediate types; and both reticulate and convex meshes appeared on seed-like Fruits of one species was regarded as an evolution type. This was a rare phenomenon in other Family and Genus of angiosperms, which was worthy of an in-depth study. According to types of the ornamentation characteristics, they had intra-specific stabilities, but significant inter-specific difference in both the macro morphology features and the ultrastructure ornamentation, which provided evidences for classification identification, discussion on their genetic relationships, introduction and cultivation and genetics and breeding. [ABSTRACT FROM AUTHOR]

Inflammasomes are one kind of important innate immune defense against viral and bacterial infections. Several inflammasome- forming sensors detect molecular patterns of invading pathogens and then trigger inflammasome activation and/or pyroptosis in infected cells, and viruses employ unique strategies to hijack or subvert inflammasome activation. Infection with herpesviruses induces the activation of diverse inflammasomes, including AIM2 and IFI16 inflammasomes; however, how Kaposi's sarcoma- associated herpesvirus (KSHV) counteracts inflammasome activation largely remains unclear. Here, we reveal that the KSHV ORF37- encoded SOX protein suppresses AIM2 inflammasome activation independent of its viral DNA exonuclease activity and host mRNA turnover. SOX interacts with the AIM2 HIN domain through the C- terminal Motif VII region and disrupts AIM2:dsDNA polymerization and ASC recruitment and oligomerization. The Y443A or F444A mutation of SOX abolishes the inhibition of AIM2 inflammasome without disrupting SOX nuclease activity, and a short SOX peptide is capable of inhibiting AIM2 inflammasome activation; consequently, infection with SOX- null, Y443A, or F444A Bac16 recombinant viruses results in robust inflammasome activation, suppressed lytic replication, and increased pyroptosis in human lymphatic endothelial cells in an AIM2- dependent manner. These results reveal that KSHV SOX suppresses AIM2 inflammasome activation to promote KSHV lytic replication and inhibit pyroptosis, representing a unique mechanism for evasion of inflammasome activation during KSHV lytic cycle. [ABSTRACT FROM AUTHOR]

The wide range power dependence of vector stimulated Brillouin scattering (SBS) gain is theoretically and experimentally characterized by a mathematical model and measurement system based on the heterodyne pump–Stokes technique. The results show that SBS phase shift is much more tolerant of pump depletion than SBS amplitude gain, hence the performance improvement of the SBS-based distributed sensing system can be achieved by measuring the SBS phase shift spectrum. The discussion about the measured Brillouin spectrum width versus pump power at different Stokes powers reveals that the occurrence of nonnegligible pump depletion imposes a restriction on the determination of pump and Stokes powers in an SBS amplitude gain-based application system. The amplitude gain and phase shift of vector SBS gain increase with the increase of pump power and decrease with the increase of Stokes power, which indicates that the design strategy with smaller Stokes power and higher pump power is reasonable. And the measured center-asymmetry of the SBS phase shift spectrum is mainly caused by the nonlinear refractive index, which puts a limitation on the maximum pump power. The obtained results can provide a useful basis for the optimal design of practical vector SBS gain-based application systems. [ABSTRACT FROM AUTHOR]

A high-accuracy Brillouin frequency shift (BFS) measurement system for vector Brillouin optical timedomain analysis-based temperature sensor is proposed, in which double sideband modulation is used and the stimulated Brillouin scattering (SBS) gain and loss processes work together to generate a superimposed SBS phase-shift spectrum. The measurement principle is analyzed by mathematical modeling and the proof-of-concept experiment is performed by using a 100-m long standard single-mode fiber. The theoretical and experimental results reveal that the temperature sensitivity of BFS obtained from the measured SBS phase-shift spectrum is 1.059 MHz∕°C, and the measurement error of temperature is only half that in traditional single sideband-based system, which indicates that the proposed technique can realize high-accuracy temperature measurement and have huge potential in the field of long-distance and high-accuracy sensing. [ABSTRACT FROM AUTHOR]

The global spread of the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the continuously emerging new variants underscore an urgent need for effective therapeutics for the treatment of coronavirus disease 2019 (COVID-19). Here, we screened several FDA-approved amphiphilic drugs and determined that sertraline (SRT) exhibits potent antiviral activity against infection of SARS-CoV-2 pseudovirus (PsV) and authentic virus in vitro. It effectively inhibits SARS-CoV-2 spike (S)-mediated cell-cell fusion. SRT targets the early stage of viral entry. It can bind to the S1 subunit of the S protein, especially the receptor binding domain (RBD), thus blocking S-hACE2 interaction and interfering with the proteolysis process of S protein. SRT is also effective against infection with SARS-CoV-2 PsV variants, including the newly emerging Omicron. The combination of SRT and other antivirals exhibits a strong synergistic effect against infection of SARS-CoV-2 PsV. The antiviral activity of SRT is independent of serotonin transporter expression. Moreover, SRT effectively inhibits infection of SARS-CoV-2 PsV and alleviates the inflammation process and lung pathological alterations in transduced mice in vivo. Therefore, SRT shows promise as a treatment option for COVID-19. [ABSTRACT FROM AUTHOR]

Kaposi’s sarcoma-associated herpesvirus (KSHV) is a g-oncogenic herpesvirus, and both lytic and latent infections play important roles in its pathogenesis and tumorigenic properties. Multiple cellular pathways and diverse mediators are hijacked by viral proteins and are used to support KSHV lytic replication. In previous studies, we revealed that KSHV ORF45 promoted KSHV transcription and translation by inducing sustained p90 ribosomal S6 kinase (RSK) activation and the phosphorylation of its substrates c-Fos and eIF4B. However, the cellular mediators required for lytic replication remain largely unknown. Here, we reveal that ORF45 activates eIF2a phosphorylation and ATF4 translation and then upregulates the expression of lysosome-associated membrane protein 3 (LAMP3) in an ATF4-dependent manner during KSHV lytic replication. Consequently, LAMP3 promotes Akt and ERK activation and then facilitates lytic gene expression and virion production. Furthermore, ATF4 enhances lytic replication through LAMP3, and LAMP3 acts in an ATF4-independent manner. Our findings suggest that the ATF4-LAMP3 axis is upregulated by ORF45 through ER stress activation during the KSHV lytic life cycle and, in turn, facilitates optimal lytic replication. IMPORTANCE The lytic replication of Kaposi’s sarcoma-associated herpesvirus (KSHV) reprograms cellular transcription and translation to generate viral proteins and virion particles. Here, we show that the mediator of ER stress ATF4 and the expression of the downstream gene LAMP3 are upregulated by ORF45 during lytic replication. Consequently, increased LAMP3 expression activates Akt and ERK and promotes lytic replication. Although several UPR transcription factors are able to promote KSHV lytic replication, the proviral effect of ATF4 on lytic replication is attenuated by LAMP3 silencing, whereas the effect of LAMP3 does not directly require ATF4 expression, indicating that LAMP3 primarily exerts effects on KSHV lytic replication downstream of ATF4 and ER stress. Taken together, our findings suggest that the ORF45-upregulated ATF4-LAMP3 axis plays an essential role in KSHV lytic replication. [ABSTRACT FROM AUTHOR]

Context: Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disease that is closely related to inflammation and apoptosis. The traditional Chinese medicine compound preparation Huangqin decoction (HQD) has been widely used in the clinical treatment of UC, but the specific mechanism of its function is still inconclusive. Objective: To explore the pathogenesis of UC based on the IFN-γ/JAK/ETS signalling pathway, and to clarify the biological mechanism of HQD. Materials and methods: Forty 8-week-old male C57BL/6 mice were randomly divided into four groups: normal control, model, model + salazosulfapyridine group (500 mg/kg, p.o., pd) and model + HQD (9.1 g/kg, p.o., pd). Using Dextran sulphate sodium (DSS) salt (2.5%, p.o.)+high-fat diet + hot and humid environment to build a mouse model of UC. One month later, the changes of colon morphology, serum inflammatory factors, intestinal epithelial cell apoptosis and IFN-γ/JAK/ETS signalling pathway related protein changes in mice were observed. Results: Compared with the model group, HQD significantly reduced the pathological score of the model mice's colon (2.60 ± 0.25 vs. 4.80 ± 0.37), and reduced the serum IFN-γ (200.30 ± 8.45 vs. 413.80 ± 6.97) and other inflammatory factors, and reduced intestinal epithelial cell apoptosis (24.85 ± 4.87 vs. 214.90 ± 39.21). In terms of mechanism, HQD down-regulated IFN-γ/JAK/ETS signalling pathway related proteins in colon tissue of UC model mice. Conclusions: These data indicate that HQD can improve UC by reducing intestinal inflammation and apoptosis, providing experimental evidence for the wide application of HQD in clinical practice of UC. [ABSTRACT FROM AUTHOR]

The article discusses degeneration of the knee as it relates to osteoarthritis in elderly men and women. Radiography is used to diagnose joint-space narrowing which is present in the late stages of degeneration while magnetic resonance imaging can be used to gain a broader spectrum of knowledge on cartilage morphology and biochemistry.

The article discusses the macromolecular imaging of cartilage. The degeneration of hyaline articular cartilage is directly related to the macromolecular status so it is important for imaging techniques to be developed to detect these changes as well as further biochemical changes before the integrity of the tissue is compromised. Delayed gadolinium-enhanced magnetic resonance imaging and sodium magnetic resonance imaging can detect these changes.

Open reading frame 45 (ORF45) of Kaposi's sarcoma-associated herpesvirus (KSHV) encodes an immediate-early protein. This protein is also present in virions as a tegument protein. ORF45 protein interacts with interferon regulatory factor 7 (IRF-7) and inhibits virus-induced type I interferon production by blocking activation of IRF-7. To define further the function of ORF45 and the mechanism underlying its action, we constructed an ORF45-null recombinant virus genome (BAC-stop45) by using a bacterial artificial chromosome (BAC) system. Stable 293T cells carrying the BAC36 (wild type) and BAC-stop45 genomes were generated. When monolayers of 293T BAC36 and 293T BAC-stop45 cells were induced with 12-O-tetradecanoylphorbol-13-acetate and sodium butyrate, no significant difference was found between them in overall viral gene expression and lytic DNA replication, but induced 293T BAC-stop45 cells released 10-fold fewer virions to the medium than did 293T BAC36 cells. When ORF45-null virus was used to infect cells, lower infectivity was observed than for wild-type BAC36. These results suggest that KSHV ORF45 plays roles in both early and late stages of viral infection, probably in viral ingress and egress. [ABSTRACT FROM AUTHOR]

Biochemical and genetic approaches have been extensively used to study transcription factor (TF) functions, but their dynamic behaviors and the complex ways in which they regulate transcription in plant cells remain unexplored, particularly behaviors such as translocation and binding to DNA. Recent developments in labeling and imaging techniques provide the necessary sensitivity and resolution to study these behaviors in living cells. In this review, we present an up-to-date portrait of the dynamics and regulation of TFs under physiologically relevant conditions and then summarize recent advances in fluorescent labeling strategies and imaging techniques. We then discuss future prospects and challenges associated with the application of these techniques to examine TFs' intricate dance in living plants. [ABSTRACT FROM AUTHOR]

The integral is one of the most important foundations for modeling dynamical systems. The gauge integral is a generalization of the Riemann integral and the Lebesgue integral and applies to a much wider class of functions. In this paper, we formalize the operational properties which contain the linearity, monotonicity, integration by parts, the Cauchy-type integrability criterion, and other important theorems of the gauge integral in higher-order logic 4 (HOL4) and then use them to verify an inverting integrator. The formalized theorem library has been accepted by the HOL4 authority and will appear in HOL4 Kananaskis-9. [ABSTRACT FROM AUTHOR]

Immune thrombocytopenia (ITP) results from decreased platelet production and accelerated platelet destruction. Impaired CD4+ regulatory T-cell (Treg) compart-ment and skewed Th1 and possibly Th17 responses have been described in ITP patients. The trigger for aberrant T-cell polarization remains unknown. Because monocytes have a critical role in develop-ment and polarization of T-cell subsets, we explored the contribution of monocyte subsets in control of Treg and Th develop-ment in patients with ITP. Unlike circulat-ing classic CD14hiCD16- subpopulatlon, the CD16+ monocyte subset was ex-panded in ITP patients with low platelet counts on thrombopoietic agents and posi-tively correlated with T-cell CD4+IFN-y+ levels, but negatively with circulating CD4+CD25hiFoxp3+ and IL-17+ Th cells. Us-ing a coculture model, we found that CD16+ ITP monocytes promoted the expansion of IFN-7+CD4+ cells and concomitantly inhib-ited the proliferation of Tregs and IL-17+ Th cells. Th-1-polarizing cytokine IL-12, se-creted after direct contact of patient T-cell and CD16+ monocytes, was responsible for the inhibitory effect on Treg and IL-17+CD4+ cell proliferation. Our findings are consis-tent with ITP CD16+ monocytes promoting Th1 development, which in turn negatively regulates IL-17 and Treg induction. This underscores the critical role of CD16+ mono-cytes in the generation of potentially pathogenic Th responses In ITP. [ABSTRACT FROM AUTHOR]

The article discusses a study which quantified water and proteoglycan (PG) content in the intervertebral disc by using in vivo magnetic resonance spectroscopy (MRS). The study also evaluated a relationship between MRS-quantified water/PG content, Pfirrmann score, clinical self-assessment, and discography. Results also suggest that the water/PG peak ratio was significantly elevated in patients as well as in discs with positive discography.

IFN regulatory factor 7 (IRF7) is a potent transcription factor of type I IFNs and IFN-stimulated genes and is known as the master regulator of type I IFN-dependent immune responses. Because excessive responses could harm the host, IRF7 itself is delicately regulated at the transcriptional, translational, and posttranslational levels. Modification of IRF7 by small ubiquitin-related modifiers (SUMOs) has been shown to regulate IFN expression and antiviral responses negatively, but the specific E3 ligase needed for IRF7 SUMOylation has remained unknown. As reported in this article, we have identified the tripartite motif-containing protein 28 (TRIM28) as a binding partner of IRF7. We have demonstrated that TRIM28 also interacts with the SUMO E2 enzyme and increases SUMOylation of IRF7 both in vivo and in vitro, suggesting it acts as a SUMO E3 ligase of IRF7. Unlike the common SUMO E3 ligase, protein inhibitor of activated STAT1, the E3 activity of TRIM28 is specific to IRF7, because it has little effect on IRF7's close relative IRF3. TRIM28 is therefore, so far as we know, the first IRF7-specific SUMO E3 reported. TRIM28-mediated SUMOylation of IRF7 is increased during viral infection, and SUMOylation of transcription factors usually results in transcriptional repression. Overexpression of TRIM28 therefore inhibits IRF7 transactivation activity, whereas knockdown of TRIM28 has the opposite effect and potentiates IFN production and antiviral responses. Collectively, our results suggest that TRIM28 is a specific SUMO E3 ligase and negative regulator of IRF7. [ABSTRACT FROM AUTHOR]

Background: The pathogenesis of insulin resistance in the absence of obesity is unknown. In obesity, multiple stress kinases have been identified that impair the insulin signaling pathway via serine phosphorylation of key second messenger proteins. These stress kinases are activated through various mechanisms related to lipid oversupply locally in insulin target tissues and in various adipose depots. Methodology/Principal Findings: To explore whether specific stress kinases that have been implicated in the insulin resistance of obesity are potentially contributing to insulin resistance in non-obese individuals, twenty healthy, non-obese, normoglycemic subjects identified as insulin sensitive or resistant were studied. Vastus lateralis muscle biopsies obtained during euglycemic, hyperinsulinemic clamp were evaluated for insulin signaling and for activation of stress kinase pathways. Total and regional adipose stores and intramyocellular lipids (IMCL) were assessed by DXA, MRI and 1H-MRS. In muscle of resistant subjects, phosphorylation of JNK was increased (1.36±0.23 vs. 0.78±0.10 OD units, P,0.05), while there was no evidence for activation of p38 MAPK or IKKb. IRS-1 serine phosphorylation was increased (1.30±0.09 vs. 0.22±0.03 OD units, P,0.005) while insulin-stimulated tyrosine phosphorylation decreased (10.97±0.95 vs. 0.89±0.50 OD units, P,0.005). IMCL levels were twice as high in insulin resistant subjects (3.26±0.48 vs. 1.58±0.35% H2O peak, P≥0.05), who also displayed increased total fat and abdominal fat when compared to insulin sensitive controls. Conclusions: This is the first report demonstrating that insulin resistance in non-obese, normoglycemic subjects is associated with activation of the JNK pathway related to increased IMCL and higher total body and abdominal adipose stores. While JNK activation is consistent with a primary impact of muscle lipid accumulation on metabolic stress, further work is necessary to determine the relative contributions of the various mediators of impaired insulin signaling in this population. [ABSTRACT FROM AUTHOR]

Background and Purpose A percutaneous nephrostomy (PCN) done on the same side as a previous open nephrolithotomy is always technically challenging. A novel one-step PCN tube that allows the puncture and placement of a drainage tube to be done in a single step has been developed. The hydrophilic coating on the tube's surface significantly reduces friction and allows easier insertion. We evaluated the tube's efficiency and safety compared with the traditional fascial dilator system.Patients and Methods Sixty-five patients with a history of open nephrolithotomy were randomly allocated (with the aid of a computer-derived assignment number) into two groups to have PCN performed in one step or multiple steps. In the one-step group, a new type of PCN tube was used. In the multistep group, fascial dilators were used serially prior to tube insertion. The two groups were similar in terms of mean age, width of target calix, and baseline serum creatinine and hemoglobin concentrations. The operating times, intubation rates, and complications in the two groups were compared.Results The mean number of attempts required to access the collecting system was 1.1 ± 0.6 in the one-step group v2.3 ± 1.2 in the multistep group (P 0.002), the successful intubation rate was 96.9 v78.8 (P 0.012), the mean operating time was 10.2 ± 2.4 minutes v25.6 ± 2.8 minutes (P 0.029), and the rate of intraoperative and postoperative complications was 3.1 v15.2, respectively (P 0.019). No major complications occurred in the one-step group.Conclusions The one-step PCN tube is a convenient and efficacious method for accessing an anatomic region where open nephrolithotomy was done previously and is a simple method for nephrostomy tube placement. [ABSTRACT FROM AUTHOR]

Perturbance of endoplasmic reticulum (ER) function, either by the mutant proteins not folding correctly, or by an excessive accumulation of proteins in the organelle, will lead to the unfolded protein response (UPR) or ER overload response (EOR). The signal-transducing pathways for UPR have been identified, whereas the pathway for EOR remains to be elucidated. Our previous study demonstrated that the overexpression of reticulon 3 (RTN3, also named HAP, homologue of ASY protein) caused apoptosis with the depletion of ER Ca2+ stores. In present research, we characterized RTN3 as a novel EOR-induced protein, triggering the apoptotic signals through the release of ER Ca2+ and the elevation of cytosolic Ca2+. Our studies showed that overexpressed RTN3 induced EOR, eliciting ER-specific apoptosis with activation of caspase-12 and mitochondrial dysfunction through ER Ca2+ depletion and the sustained elevation of cytosolic Ca2+. Furthermore, we demonstrated that overexpressed RTN3 and stimuli that activate both EOR and UPR, not UPR only, were able to induce up-regulation of inducible nitric oxide synthase (iNOS) in HeLa cells through ER Ca2+ release and reactive oxygen intermediates (ROIs), resulting in endogenous calcium-dependent nitric oxide protecting cells against ER specific apoptosis, which suggested that the nitric oxide and iNOS represented a likely protective response to EOR, not the UPR. These results supported that the release of ER Ca2+ stores triggered the initial signal-transducing pathways for EOR induced by overexpressed RTN3. 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The effect of prenatal exposure to bisphenol A (BPA) on the immune system in mice was investigated. Virgin female mice were fed varying doses of BPA, on a daily basis, over a period of 18 days commencing on the day of pairing with stud males (day 0). On day 77, their male offspring of 8 weeks were immunized with hen egg lysozyme (HEL). Three weeks later, anti- HEL immunoglobulin G (IgG) in sera, and proliferative responses of spleen cells to the antigen, were measured. Anti-HEL IgG2a and interferon-γ, (IFN-γ), secreted from splenic lymphocytes, were measured as indicators of T helper 1 (Th1) immune responses, while anti-HEL IgGl and interleukin-4 (IL-4) were measured as indicators of Th2 responses. The results showed that fetal exposure to BPA was followed by significant increases in anti-HEL IgG as well as antigen-specific cell proliferation. Both Th1 responses (including anti-HEL IgG2a and IFN-γ production) and Th2 responses (including anti-HEL IgG1 and IL-4 production) were augmented by prenatal exposure to BPA, although the augmentation of Th1 responses appeared to be greater than that of Th2 responses. Two-colour flow cytometric analysis showed that mice exposed prenatally to BPA had 29% and 100% more splenic CD3+ CD4+ and CD3+ CD8+ cells, respectively, than control animals. Similar results were obtained from females whose mothers had consumed BPA during pregnancy. These results suggest that prenatal exposure to BPA may result in the up-regulation of immune responses, especially Thl responses, in adulthood. [ABSTRACT FROM AUTHOR]