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Solar wind (SW) charge exchange (CX) is an important mechanism responsible for X-ray emissions in comets' coma and many other astrophysical environments. By incorporating the experimentally derived total cross-sections and the tested state-selectivity models into the Kronos program, we generate X-ray spectra in H-like and fully stripped C, N, O ion CX collision with atomic H. Using these data, we revisit the fitting of Chandra X-ray data of Comet C/1999 S4 by considering the typical SW collision energies of 0.8 and 3 keV/u, respectively. Our results are in an excellent agreement with the astrophysical observation. We find that charge exchange between C5+,6+, N6+,7+, O7+,8+ and H significantly contributes to the comet's spectrum ranging from 300 to 800 eV for both slow and fast SW ions, where N7+ abundance is underestimated in previous studies. [ABSTRACT FROM AUTHOR]

The emergence of linezolid‐resistant (LR) enterococci found in food of animal origin arouses attention, but little is known about LR enterococci in fur animals. A total of 342 Enterococcus faecalis and 265 E. faecium strains isolated from fur animals in China from 2015 to 2017 were investigated to determine if LR enterococci (≥16 μg ml−1) are present. Overall, two E. faecalis and 12 E. faecium among these isolates were resistant to linezolid. In addition, all LR isolates were classified as multidrug‐resistant isolates. We further explore the resistance genes of the LR enterococci, four E. faecalis and two E. faecium isolates contained optrA gene. Two of them co‐harboured optrA and poxtA genes. We detected virulence genes in LR enterococci were the following: asa1, cylA, esp, gelE and hyl, among which the highest carrying rate gene was asa1. Besides, all of the LR enterococci we tested had the biofilm‐forming ability. It is worth noting that we detected a novel ST type ST2010 from E. faecium 82‐2. These data show LR enterococci exist in fur animals and have unique characteristics. [ABSTRACT FROM AUTHOR]

Summary: Background: Dupilumab is an antibody against interleukin‐4 receptor α, used in the treatment of atopic dermatitis (AD). Objectives: To evaluate the efficacy and safety of dupilumab in adult Chinese patients with moderate‐to‐severe AD. Methods: In this randomized, double‐blind, placebo‐controlled, parallel‐group, phase III study, conducted between December 2018 and February 2020, patients with AD received dupilumab (300 mg) or placebo once every 2 weeks for 16 weeks, and were followed up for 12 weeks. The primary efficacy endpoint was the proportion of patients with both an Investigator's Global Assessment score of 0–1 and a reduction from baseline of ≥ 2 points at week 16. Results: Overall, 165 patients (mean age 30·6 years; 71·5% male patients) were randomized; 82 patients were randomized to dupilumab and 83 patients were randomized to placebo. At week 16, 26·8% of patients in the dupilumab group and 4·8% of patients in the placebo group achieved the primary endpoint [difference 22·0%, 95% confidence interval (CI) 11·37–32·65; P < 0·001]. Compared with placebo, higher proportions of patients in the dupilumab group achieved ≥ 75% reduction in the Eczema Area and Severity Index score (57·3% vs. 14·5%; difference 42·9%, 95% CI 29·75–55·97; P < 0·001) and had ≥ 3‐point (52·4% vs. 9·6%; difference 42·8%, 95% CI 30·26–55·34; P < 0·001) and ≥ 4‐point (39·0% vs. 4·8%; difference 34·2%, 95% CI 22·69–45·72; P < 0·001) reductions in weekly average daily peak daily pruritus numerical rating scale scores. The incidence of treatment‐emergent adverse events during the treatment period was similar in the two groups. The incidence of conjunctivitis, allergic conjunctivitis and injection site reaction was higher in the dupilumab group than in the placebo group. Conclusions: In adult Chinese patients, dupilumab was effective in improving the signs and symptoms of AD and demonstrated a favourable safety profile. What is already known about this topic?Two randomized, placebo‐controlled phase III trials (SOLO 1 and SOLO 2) have demonstrated that dupilumab is effective and safe when used in the treatment of atopic dermatitis in adults.However, very few Chinese participants were included and, therefore, the efficacy and safety of dupilumab in this population is unclear. What does this study add?The findings of this randomized, placebo‐controlled phase III trial show that dupilumab is effective in improving the signs and symptoms of atopic dermatitis in adult Chinese patients and has a favourable safety profile in this population. Plain language summary available online [ABSTRACT FROM AUTHOR]

Charge exchange has been recognized as a primary source of soft X-ray emission in many astrophysical outflow environments, including cometary and planetary exospheres impacted by the solar wind. Some models have been set up by using different data collections of charge-exchange cross-sections. However, multiple-electron transfer has not been included in these models. In this paper, we set up a charge-exchange model with the inclusion of double-electron capture (DEC), and make a detailed investigation of this process on X-ray emissions of highly charged carbon, nitrogen, oxygen, and neon ions by using available experimental cross-sections. We also study the effect of different n- selective cross-sections on soft X-ray emission by using available experimental n -distributions. This work reveals that DEC enhancement on line intensity is linearly proportional to the ratio of ion abundance in the solar wind. It is more obvious for soft X-rays from carbon ions (C4+) in collision with CO2, and the enhancement on line intensity can be up to 53 per cent with typical ion abundances [ Advanced Composition Explorer (ACE)] in the solar wind. The synthetic spectra with parameters from the Ulysses mission for the solar wind reveal velocity dependence, target dependence, as well as the non-negligible contribution from the DEC. [ABSTRACT FROM AUTHOR]

The main goal of pulsar timing array experiments is to detect correlated signals such as nanohertz-frequency gravitational waves. Pulsar timing data collected in dense monitoring campaigns can also be used to study the stars themselves, their binary companions, and the intervening ionized interstellar medium. Timing observations are extraordinarily sensitive to changes in path-length between the pulsar and the Earth, enabling precise measurements of the pulsar positions, distances and velocities, and the shapes of their orbits. Here we present a timing analysis of 25 pulsars observed as part of the Parkes Pulsar Timing Array (PPTA) project over time spans of up to 24 yr. The data are from the second data release of the PPTA, which we have extended by including legacy data. We make the first detection of Shapiro delay in four Southern pulsars (PSRs J1017−7156, J1125−6014, J1545−4550, and J1732−5049), and of parallax in six pulsars. The prominent Shapiro delay of PSR J1125−6014 implies a neutron star mass of Mp = 1.5 ± 0.2 M⊙ (68 per cent credibility interval). Measurements of both Shapiro delay and relativistic periastron advance in PSR J1600−3053 yield a large but uncertain pulsar mass of |$M_p = 2.06^{+0.44}_{-0.41}$|  M⊙ (68 per cent credibility interval). We measure the distance to PSR J1909−3744 to a precision of 10 lyr, indicating that for gravitational wave periods over a decade, the pulsar provides a coherent baseline for pulsar timing array experiments. [ABSTRACT FROM AUTHOR]

Summary: Sepsis is an intractable clinical syndrome characterized by organ dysfunction when the body over‐responds to an infection. Sepsis has a high fatality rate and lacks effective treatment. Family with sequence similarity 96 member A (FAM96A) is an evolutionarily conserved protein with high expression in the immune system and is related to cytosolic iron assembly and tumour suppression; however, research has been rarely conducted on its immune functions. Our study found that Fam96a−/− mice significantly resisted lesions during sepsis simulated by caecal ligation and puncture (CLP) or endotoxicosis models. After a challenge with lipopolysaccharide (LPS) or infection, Fam96a−/− mice exhibited less organ damage, longer survival and better bacterial clearance with decreased levels of proinflammatory cytokines. While screening several subsets of immune cells, FAM96A‐expressing macrophages as the key cell type inhibited sepsis development. In‐vivo macrophage depletion or adoptive transfer experiments abrogated significant differences in the survival of sepsis between Fam96a−/− and wild‐type mice. Results of the bone marrow‐derived macrophage (BMDM) polarization experiment indicated that FAM96A deficiency promotes the transformation of uncommitted monocytes/macrophages (M0) into M2 macrophages, secreting fewer proinflammatory cytokines. FAM96A may mediate an immunometabolism shift – from oxidative phosphorylation (OXPHOS) to glycolysis – in macrophages during sepsis, mirrored by reactive oxygen species (ROS) and glucose uptake. These data demonstrate that FAM96A regulates inflammatory response and provide a novel genomic insight for sepsis treatment. [ABSTRACT FROM AUTHOR]

Cosmic strings are potential gravitational-wave (GW) sources that can be probed by pulsar timing arrays (PTAs). In this work we develop a detection algorithm for a GW burst from a cusp on a cosmic string, and apply it to Parkes PTA data. We find four events with a false alarm probability less than 1 per cent. However further investigation shows that all of these are likely to be spurious. As there are no convincing detections we place upper limits on the GW amplitude for different event durations. From these bounds we place limits on the cosmic string tension of G μ ∼ 10−5, and highlight that this bound is independent from those obtained using other techniques. We discuss the physical implications of our results and the prospect of probing cosmic strings in the era of Square Kilometre Array. [ABSTRACT FROM AUTHOR]

Summary: NOD‐like receptor pyrin 7 (NLRP7) has been identified as the major gene responsible for the recurrent hydatidiform mole (RHM). The immunological role of NLRP7 mutation in HM patients has not been conclusively demonstrated. Hence, we aim to demonstrate this role in our study. We followed 12 new patients with NLRP7 non‐synonymous variations (NSVs) from date to date. Peripheral blood mononuclear cells (PBMCs) were collected separately from patients with and without NLRP7 mutation. Supernatant interleukin (IL)‐1β secretion, intracellular pro‐IL‐1β and mature IL‐1β expressions were measured after 24 h lipopolysaccharide (LPS) stimulation. Plasmids with corresponding NSVs were generated to evaluate the ability of processing pro‐IL‐1β into mature IL‐1β in vitro. Homozygous or compound heterozygous NLRP7 mutations secreted less IL‐1β in roots of abnormal intracellular pro‐IL‐1β or mature IL‐1β, according to different domains. Plasmids with NSVs could also affect processing or/and trafficking together with caspase‐1 and apoptosis‐associated speck‐like protein (ASC). Inflammasome‐related NLRP7 mutation is a potential mechanism of RHM. [ABSTRACT FROM AUTHOR]

Candida albicans is an opportunistic fungus, which causes vulvovaginal candidiasis (VVC). The aim of this study was to evaluate Mrr2 mutation and its expression levels and Candida drug resistance 1 (Cdr1) in C. albicans associated with fluconazole (FCA) resistance. We identified 80 isolates of C. albicans from 155 vaginal secretions and performed FCA drug sensitivity tests, using M27‐A3 micro‐broth dilution. We extracted DNA, sequenced Mrr2, and performed reverse transcriptase‐quantitative PCR polymerase chain reaction (RT‐qPCR) to detect mRNA expression levels of Mrr2 and Cdr1. In total, 40 isolates were sensitive, 10 were dose‐dependently sensitive, and 30 were resistant to FCA. Mrr2 mutation occurred in 56·67% isolates, which was significantly higher than that in the FCA sensitive group (26·08%, P < 0·05). The mRNA expression level of Cdr1 in the FCA resistant group was significantly higher than that in the sensitive group Cdr1 (0·42 ± 0·294 vs 0·25 ± 0·289, P < 0·05). The odds ratio of FCA‐resistant occurrence in C. albicans with Mrr2 mutation and high expression levels was 47·5 times higher than C. albicans without Mrr2 mutation and low expression levels. The results may provide new insights for improving VVC treatment. Significance and Impact of the Study: Significance and Impact of the Study: Candida albicans is an opportunistic fungus, which causes vulvovaginal candidiasis (VVC). Fluconazole (FCA) is the most widely used drug in VVC infection. However, the widespread use of FCA has severely increased the incidence of FCA‐resistant fungus. Therefore, the mechanism underlying FCA resistance in C. albicans must be elucidated urgently. This study demonstrated that high expression of Cdr1 and Mrr2 may directly be linked to C. albicans resistance to FCA, and high expression of Mrr2 may promote high expression of Cdr1 and mediate resistance of C. albicans to FCA. The results may provide new insights for improving VVC treatment. [ABSTRACT FROM AUTHOR]

Summary: Background: Dupilumab (monoclonal antibody inhibiting IL‐4/IL‐13 signalling) is approved for use in adolescents aged ≥ 12 years with inadequately controlled moderate‐to‐severe atopic dermatitis (AD). Dupilumab significantly improved AD signs/symptoms in a 16‐week, randomised, placebo‐controlled phase III trial in adolescents (NCT03054428). Objectives: To characterize the pharmacokinetics of dupilumab, and long‐term safety and efficacy in adolescents. Methods: This was a global, multicentre, phase IIa, open‐label, ascending‐dose, sequential cohort study with a phase III open‐label extension (OLE) in adolescents with moderate‐to‐severe AD. In the phase IIa study, patients received one dupilumab dose (2 mg kg−1 or 4 mg kg−1) and 8 weeks of pharmacokinetic sampling. Thereafter, patients received the same dose weekly for 4 weeks, with 8‐week safety follow‐up. Patients then enrolled in the OLE, continuing 2 mg kg−1 or 4 mg kg−1 dupilumab weekly. Primary end points were dupilumab concentration–time profile and incidence of treatment‐emergent adverse events (TEAEs). Secondary outcomes included Eczema Area and Severity Index (EASI). Results: Forty adolescents received dupilumab in the phase IIa study; 36 enrolled in the OLE. Dupilumab showed nonlinear, target‐mediated pharmacokinetics. Mean ± SD trough dupilumab concentrations in serum at week 48 (OLE) were 74 ± 19 mg L−1 and 161 ± 60 mg L−1 for 2 mg kg−1 and 4 mg kg−1, respectively. Dupilumab was well tolerated over 52 weeks; the most common TEAEs were nasopharyngitis (week 52: 41% [2 mg kg−1], 47% [4 mg kg−1]) and AD exacerbation (29%, 42%). After one dupilumab dose in the phase IIa study, EASI improved from baseline to week 2 [mean ± SD reduction −34% ± 20% (2 mg kg−1) and −51% ± 29% (4 mg kg−1)]. With continuing treatment, EASI scores improved further [week 52: −85% ± 12% (2 mg kg−1) and −84% ± 20% (4 mg kg−1)]. Conclusions: In adolescents with moderate‐to‐severe AD, dupilumab's pharmacokinetic profile was similar to that in adults. These 52‐week safety and efficacy data support long‐term use of dupilumab in this patient population. What's already known about this topic? Adolescents with moderate‐to‐severe atopic dermatitis (AD) have high unmet medical need, with significant disease burden and limited treatment options.Dupilumab (monoclonal antibody against interleukin‐4 receptor α) is approved for the treatment of adolescents with moderate‐to‐severe AD who are inadequately responsive to standard of care (U.S.A.) or candidates for systemic therapy (European Union).A 16‐week, randomized, placebo‐controlled phase III trial in adolescents demonstrated significant improvements in AD signs/symptoms with an acceptable safety profile. What does this study add? These studies demonstrate the long‐term safety and efficacy of dupilumab in adolescents with moderate‐to‐severe AD for up to 52 weeks of treatment, thus extending and reinforcing the findings from the 16‐week dupilumab phase III trial.The data from these studies also support the use of dupilumab in combination with current standard of care (topical corticosteroids), which was not evaluated in the 16‐week phase III monotherapy trial. Linked Comment: Sibbald. Br J Dermatol 2020; 182:12–13. Plain language summary available online [ABSTRACT FROM AUTHOR]

Summary: Background: Dupilumab blocks the shared receptor component for interleukin (IL)‐4 and IL‐13. It is approved in the U.S.A. for patients aged ≥ 12 years with moderate‐to‐severe atopic dermatitis (AD) uncontrolled by topical prescription medicines or who cannot use topical medicines, for patients in Japan whose AD is uncontrolled with existing therapies, for patients with moderate‐to‐severe AD in Europe who are candidates for systemic therapy and for patients aged ≥ 12 years for maintenance treatment of moderate‐to‐severe asthma uncontrolled with their current medicines. AD trials have reported increased incidence of conjunctivitis for dupilumab vs. placebo. Objectives: To characterize further the occurrence and risk factors of conjunctivitis in dupilumab clinical trials. Methods: We evaluated randomized placebo‐controlled trials of dupilumab in AD (n = 2629), asthma (n = 2876), chronic rhinosinusitis with nasal polyps (CRSwNP) (n = 60) and eosinophilic oesophagitis (EoE) (n = 47). Results: In most AD trials, dupilumab‐treated patients had higher conjunctivitis incidence than placebo controls. Higher baseline AD severity and previous history of conjunctivitis were associated with increased conjunctivitis incidence. Conjunctivitis was mostly mild to moderate. Most cases recovered or resolved during the treatment period; two patients permanently discontinued dupilumab due to conjunctivitis or keratitis. Common treatments included ophthalmic corticosteroids, antibiotics, and antihistamines or mast cell stabilizers. Most cases were diagnosed by the investigators. In asthma and CRSwNP trials, the incidence of conjunctivitis was lower for both dupilumab and placebo than in AD trials; dupilumab did not increase the incidence compared with placebo. In the EoE trial, no patients had conjunctivitis. Conclusions: Conjunctivitis was more frequent with dupilumab treatment in most AD trials. In dupilumab trials in other type 2 diseases, incidence of conjunctivitis was overall very low, and was similar for dupilumab and placebo. In AD, the incidence of conjunctivitis was associated with AD severity and prior history of conjunctivitis. The aetiology and treatment of conjunctivitis in dupilumab‐treated patients require further study. What's already known about this topic? Ocular disorders, including allergic conjunctivitis, are common in patients with atopic dermatitis (AD).In most dupilumab AD trials, dupilumab‐treated patients had higher conjunctivitis incidence than those receiving placebo.Most cases were mild to moderate and recovered or were recovering during study treatment; study treatment discontinuation due to conjunctivitis was rare.Conjunctivitis incidence was very low and similar for dupilumab and placebo in clinical trials in asthma, chronic rhinosinusitis with nasal polyps and eosinophilic oesophagitis. What does this study add? This analysis confirms and extends the results of the individual clinical trials.Baseline disease‐related factors, including AD severity, prior conjunctivitis history and certain biomarkers (thymus and activation‐regulated chemokine, IgE, eosinophils), were associated with increased incidence of conjunctivitis.Patients who responded well to dupilumab had reduced incidence of conjunctivitis.Further study is needed to elucidate the aetiology and treatment of conjunctivitis in dupilumab‐treated patients with AD. Linked Editorial: Chia‐Yu Chu. Br J Dermatol 2019; 181:436–437. Plain language summary available online Respond to this article [ABSTRACT FROM AUTHOR]

Aims: Spodoptera exigua is a serious pest of many agricultural crops. However, the bacterial communities of S. exigua are poorly studied, particularly over their entire life cycle. We aimed to study the biodiversity of the microbiota across the life cycle of S. exigua and to provide a better and obtain insight into new pest control strategies. Methods and Results: The bacterial diversity across the life cycle of S. exigua was studied using Illumina MiSeq sequencing of 16S rRNA genes. Spodoptera exigua is dominated by Proteobacteria and Firmicutes, with a total relative abundance of 90·03%. Enterococcus (24·6%), Pseudomonas (12·2%) and Asaia (45·9%) were abundant and active in eggs, while Methylobacterium (18·7%) and Halomonas (16·5%) dominated freshly eclosed larvae. The 3rd and 5th instar larvae were dominated by Enterococcus (76·3 and 62·0%). Pupal stages had the highest microbial diversity. There was no significant difference between newly emerged males and females. Symbionts of eggs were extremely similar and probably vertically transmitted by males during mating. Conclusions: The result showed that the bacterial community was affected by the host developmental stages. Our results also suggest that symbionts of egg mass are probably vertically transmitted control by male spawning adults. Significance and Impact of the Study: Our study documents the symbiont bacteria across the life cycle of S. exigua. Understanding the microbial symbionts may provide clues to develop potential biocontrol techniques against this pest. [ABSTRACT FROM AUTHOR]

Summary: Background: Dermatomyositis (DM) is an autoimmune disease affecting primarily the skin, muscle and lung. Dysregulations of cytokines and chemokines are commonly found in inflammatory disorders. Objectives: To investigate the association between serum cytokines and chemokines and clinical severity, especially cutaneous lesions and interstitial lung disease (ILD) in patients with DM and clinically amyopathic DM (CADM). Methods: Clinical features, laboratory findings and serum of 40 patients with DM or CADM were collected and analysed. Serum cytokines and chemokines were measured by enzyme‐linked immunosorbent assay or cytometric bead array. A multiple unpaired t‐test was performed to compare cytokines and chemokines in patients with DM and healthy controls. Correlations of serum cytokines and chemokines with disease severity were evaluated by Spearman's rank correlation test. Results: Serum interferon (IFN)‐β [rs = 0·37, 95% confidence interval (CI) 0·078–0·62; P = 0·019] and CXCL10 (rs = 0·32, 95% CI to −0·004 to 0·57; P = 0·045) were significantly correlated with the Cutaneous Dermatomyositis Disease Area and Severity Index activity score in the subset of patients with DM or CADM. Serum levels of interleukin (IL)‐6, IL‐10, IL‐18 and IFN‐β were significantly higher in the patients with acute/subacute interstitial pneumonia (A/SIP) than in the subset without A/SIP (P < 0·05). IL‐6 (rs = 0·54, 95% CI 0·27–0·72; P < 0·001) and IL‐18 (rs = 0·46, 95% CI 0·21–0·65; P = 0·003) were significantly correlated with the serum level of anti‐melanoma differentiation‐associated protein 5 antibody. Conclusions: Serum levels of IFN‐β and CXCL10 may be useful biomarkers for assessing cutaneous disease activity in patients with DM and CADM. In addition, serum IL‐6, IL‐10, IL‐18 and IFN‐β were highly correlated with the occurrence of A/SIP. These cytokines may play a role in the pathogenesis of DM and CADM. What's already known about this topic? The mechanism of cutaneous manifestations in dermatomyositis (DM) and clinically amyopathic DM (CADM) has not yet been elucidated.Cellular immunity, cytokine pathways, mechanical stress and sun exposure are possible contributors.The correlation between serum cytokines and chemokines and disease activity, including Cutaneous Dermatomyositis Disease Area and Severity Index and anti‐melanoma differentiation‐associated protein (MDA)5 antibody, remains to be explored further. What does this study add? Serum interleukin (IL)‐6, IL‐10, IL‐18 and interferon (IFN)‐β were highly correlated with the occurrence of acute/subacute interstitial pneumonia (A/SIP).Serum levels of IL‐6 and IL‐18 were significantly correlated with anti‐MDA5 antibody, indicating that IL‐6 and IL‐18 may contribute to anti‐MDA5 antibody‐associated A/SIP.We report the correlation between cytokines and serum levels of anti‐MDA5 antibody among Chinese patients with DM and CADM. What is the translational message? Serum levels of IFN‐β and CXCL10 may be useful biomarkers for assessing cutaneous disease activity in patients with DM and CADM. Plain language summary available online [ABSTRACT FROM AUTHOR]

Summary: The objective of the present study was to evaluate the role of CDKN1A in rheumatoid arthritis (RA). Related gene expression data screened from Gene Expression Omnibus (GEO) were processed with network analysis. Protein–protein interaction was analysed through string database. Quantitative reverse transcription–polymerase chain reaction (qRT–PCR) was used to measure mRNA and microRNA expression. Cell proliferation and cell cycle were tested by MTT assay and flow cytometry, respectively. Transwell migration and invasion assay was used to test cell migration and invasion. CDKN1A screened by bioinformatics methods showed differential expression in RA cells compared with healthy controls (HC), and was at an important position in the protein–protein interaction network of RA. Compared with the HC group, CDKN1A was down‐regulated in human RA synovium tissues and human fibroblast‐like synoviocytes (HFLS). Contrary to CDKN1A silencing, CDKN1A over‐expression significantly inhibited the proliferation and invasion of HFLS‐RA, arrested HFLS‐RA in G0/G1 phase and down‐regulated the expressions of tumour necrosis factor (TNF)‐α and interleukin (IL)‐6, while it up‐regulated the expression of IL‐10. CDKN1A over‐expression could also suppress phosphorylated signal transducers and activators of transcription 1 (pSTAT‐1) expression. MiR‐146a, highly expressed in RA tissues, could regulate CDKN1A negatively. Anti‐146a suppressed cell proliferation and invasion, and at the same time enhanced IL‐10 expression but inhibited IL‐6, TNF‐α and pSTAT‐1 expression. The results indicated that CDKN1A over‐expression, which could be enhanced by miR‐146a suppression, inhibited the proliferation of invasion in HFLS‐RA. This was probably a result of suppressed pSTAT‐1, IL‐6 and TNF‐α expression and enhanced IL‐10 expression. The objective of the present study was to evaluate the role of CDKN1A in rheumatoid arthritis (RA). The results indicated that CDKN1A overexpression, which could be enhanced by miR‐146a suppression, inhibited the proliferation, invasion in HFLS‐RA. This was probably a result of suppressed pSTAT1, IL6 and TNFα expression and enhanced IL10 expression. [ABSTRACT FROM AUTHOR]

Renal fibrosis is the common final manifestation of chronic kidney diseases and usually results in end-stage renal failure. In this study, we evaluated the effect of fingolimod (FTY720), an analogue of sphingosine 1-phosphate (S1P), as a treatment for the unilateral ureteral obstruction (UUO)-induced renal fibrosis animal model. We treated mice with FTY720 at a dosage of 1 mg/kg/day by intragastric administration from day 1 until day 7. The control group received the same amount of saline. FTY720 reduced significantly the urine albumin/creatinine ratio (UACR) in treated UUO mice. FTY720 treatment also caused a significant decrease in interstitial expansion and collagen deposition in the kidney, accompanied by reduced mononuclear cell recruitment and inflammatory cytokine expression. In addition, the expression levels of the endothelial cell adhesion molecules P-selectin and vascular cell adhesion protein 1 (VCAM-1) were suppressed in the ligated kidney by FTY720 administration, suggesting reduced renal endothelial cell activation. Furthermore, in renal interstitial fibroblast normal rat kidney (NRK)-49F cells, FTY720 significantly affected transforming growth factor (TGF)-β-induced α-smooth muscle actin (SMA) expression and collagen synthesis by inhibiting both the Mothers against decapentaplegic homologue (Smad)2/3 and phosphatidylinositol 3-kinase/protein kinase B/glycogen synthase kinase 3 beta (PI3K/AKT/GSK3β) signalling pathways. S1P1 knock-down by siRNA reversed this effect significantly in our fibroblast cell culture model. Therefore, FTY720 attenuates renal fibrosis via two different mechanisms: first, FTY720 suppresses the synthesis of extracellular matrix in interstitial fibroblasts by interfering with TGF-β signalling; and secondly, FTY720 affects endothelial cell activation and chemokine expression, thereby reducing immune cell recruitment into the kidney. [ABSTRACT FROM AUTHOR]

A pulsar timing array is a Galactic-scale detector of nanohertz gravitational waves (GWs). Its target signals contain two components: the 'Earth term' and the 'pulsar term' corresponding to GWs incident on the Earth and pulsar, respectively. In this work we present a Frequentist method for the detection and localization of continuouswaves that takes into account the pulsar term and is significantly faster than existing methods. We investigate the role of pulsar terms by comparing a full-signal search with an Earth-term-only search for non-evolving black hole binaries. By applying the method to synthetic data sets, we find that (i) a full-signal search can slightly improve the detection probability (by about five per cent); (ii) sky localization is biased if only Earth terms are searched for and the inclusion of pulsar terms is critical to remove such a bias; (iii) in the case of strong detections (with signal-to-noise ratio ≳30), it may be possible to improve pulsar distance estimation through GW measurements. [ABSTRACT FROM AUTHOR]

By regularly monitoring the most stable millisecond pulsars over many years, pulsar timing arrays (PTAs) are positioned to detect and study correlations in the timing behaviour of those pulsars. Gravitational waves (GWs) from supermassive black hole binaries (SMBHBs) are an exciting potentially detectable source of such correlations. We describe a straightforward technique by which a PTAcan be 'phased-up' to form time series of the two polarization modes of GWs coming from a particular direction of the sky. Our technique requires no assumptions regarding the time-domain behaviour of a GW signal. This method has already been used to place stringent bounds on GWs from individual SMBHBs in circular orbits. Here, we describe the methodology and demonstrate the versatility of the technique in searches for a wide variety of GW signals including bursts with unmodelled waveforms. Using the first six years of data from the Parkes Pulsar Timing Array, we conduct an all-sky search for a detectable excess of GW power from any direction. For the lines of sight to several nearby massive galaxy clusters, we carry out a more detailed search for GW bursts with memory, which are distinct signatures of SMBHB mergers. In all cases, we find that the data are consistent with noise. [ABSTRACT FROM AUTHOR]

The study aims to evaluate the safety and availability of totally minimally invasive Ivor- Lewis esophagectomy ( MIIE) with single-utility incision video-assisted thoracoscopic surgery. Forty-one patients with mid-lower thoracic esophageal cancer were prospectively treated with totally MIIE. Two stages of laparoscopic-thoracoscopic procedures were performed. The first 29 patients were treated with four-port video-assisted thoracoscopic surgery (Group 1); the others were treated with single-utility incision video-assisted thoracoscopic surgery (Group 2). Short-term clinicopathological outcomes were examined. All patients had negative tumor margins and were pathologically staged from T1N0M0 to T3N2M0. Among Group 1, there was one conversion to open surgery. The mean duration of surgery was 268.4 ± 37.8 minutes, and mean blood loss was 207.2 ± 74.1 mL without significant differences between groups. The average thoracic or abdominal lymph node yield was 12.6 ± 7.1 or 6 ± 5.8, respectively. The median postoperative hospital stay was 7 days. No mortalities occurred. Minor morbidity complicated by late-stage gastroparesis occurred in two patients (4.9%) after discharge. Major morbidities, including intestinal obstruction and anastomotic leakage, occurred in three patients (7.3%) after discharge. Among Group 2, the average operative duration was 275.4 ± 31.2 minutes, and the mean blood loss was 220 ± 94.9 mL. One patient developed late-stage anastomotic leakage. The average thoracic or abdominal lymph node yield was 14.7 ± 8.8 and 6.3 ± 5.7, respectively. No statistically significant differences were identified between Group 1 and Group 2. MIIE with single-utility incision video-assisted thoracoscopic surgery is feasible in patients with mid-lower thoracic esophageal cancer without compromising the extent of surgical resection and perioperative outcomes. [ABSTRACT FROM AUTHOR]

Alteration of gene expression tightly regulates lipogenesis. Stearoyl-CoA desaturase-1 (SCD-1), a key enzyme in lipogenesis, catalyzes the conversion of SFA to MUFA, and inhibition of its activity impairs lipid synthesis. As posttranscriptional regulators, microRNAs are involved in many pathways of lipid metabolism; however, their effect on SCD-1 has not been reported. In this study, miR-125b was identified as a potential regulator of SCD-1 using bioinformatics analysis. Here, we validated SCD-1 as the target of miR-125b using a dual luciferase assay. During adipogenesis, a synthetic mimic or inhibitor was used to overexpress or reduce the expression of miR-125b in porcine adipocytes. Overexpression of miR-125b reduced the accumulation of lipid droplets and triglycerides concentration and repressed SCD-1 protein expression and MUFA composition. The inhibitor had the reverse effect. Small interfering RNA against SCD-1 tested in adipocytes further proved the direct correlation between miR-125b and SCD-1. Moreover, in vivo experiments in mice showed that injection of miR-125b expression vector decreased the hepatic triglycerides concentration relative to saline. This study indicated that miR-125b regulates lipogenesis by targeting SCD-1; therefore, miR-125b might be applied in therapy of lipid metabolism disorders. [ABSTRACT FROM AUTHOR]

Background Paraneoplastic pemphigus ( PNP) involves multiple organs, but little is known about its neurological involvement. Objectives To investigate the symptoms, prognosis and profiles of associated autoantibodies in myasthenia gravis ( MG), and their correlations in patients with PNP. Methods Fifty-eight patients with PNP were assessed for myasthenic symptoms and laboratory evidence. Serum autoantibodies against acetylcholine receptor ( AChR), acetylcholinesterase ( AChE), titin, ryanodine receptor (RyR) and muscle-specific kinase (Mu SK) were measured by enzyme-linked immunosorbent assay. Patients with pemphigus vulgaris ( PV), pemphigus foliaceus ( PF), connective tissue disease ( CTD) and non- PNP MG ( NP- MG), and healthy donors, served as controls. These autoantibodies in PNP were also compared in the presence or absence of dyspnoea or muscle weakness. Cox regression and log-rank tests were used for survival analysis. Results Overall 39% of patients with PNP experienced muscle weakness, and 35% were diagnosed with MG. Moreover, 35% had positive anti- AChR and 28% had anti- AChE antibodies, similarly to NP- MG (33% and 17%, respectively, P > 0·05). However, both were negative in all patients with PV, PF and CTD and healthy donors ( P < 0·005). No other antibodies showed significant differences among groups. Anti- AChR and anti- AChE antibody levels were significantly increased in patients with PNP with dyspnoea, while anti- AChR, anti-titin and anti-RyR were significantly increased in patients with PNP with muscle weakness ( P < 0·05). Nevertheless, levels and positive rates of these autoantibodies showed no significant differences between PNP with Castleman disease and thymoma. Although anti- AChE levels impacted survival duration ( P = 0·027, odds ratio 3·14), MG complications did not affect the overall survival percentage in PNP. Conclusions MG is a complication of PNP. Anti- AChR and anti- AChE antibodies are prominent in patients with PNP, especially those with dyspnoea. [ABSTRACT FROM AUTHOR]

We present results of an all-sky search in the Parkes Pulsar Timing Array (PPTA) Data Release 1 data set for continuous gravitational waves (GWs) in the frequency range from 5 × 10−9 to 2 × 10−7 Hz. Such signals could be produced by individual supermassive binary black hole systems in the early stage of coalescence. We phase up the pulsar timing array data set to form, for each position on the sky, two data streams that correspond to the two GW polarizations and then carry out an optimal search for GW signals on these data streams. Since no statistically significant GWs were detected, we place upper limits on the intrinsic GW strain amplitude h0 for a range of GW frequencies. For example, at 10−8 Hz our analysis has excluded with 95 per cent confidence the presence of signals with h0 ≥ 1.7 × 10−14. Our new limits are about a factor of 4 more stringent than those of Yardley et al. based on an earlier PPTA data set and a factor of 2 better than those reported in the recent Arzoumanian et al. paper. We also present PPTA directional sensitivity curves and find that for the most sensitive region on the sky, the current data set is sensitive to GWs from circular supermassive binary black holes with chirp masses of 109 M⊙ out to a luminosity distance of about 100 Mpc. Finally, we set an upper limit of 4 × 10−3 Mpc−3 Gyr−1 at 95 per cent confidence on the coalescence rate of nearby (z ≲ 0.1) supermassive binary black holes in circular orbits with chirp masses of 1010 M⊙. [ABSTRACT FROM AUTHOR]

High-sensitivity radio-frequency observations of millisecond pulsars usually show stochastic, broad-band, pulse-shape variations intrinsic to the pulsar emission process. These variations induce jitter noise in pulsar timing observations; understanding the properties of this noise is of particular importance for the effort to detect gravitational waves with pulsar timing arrays. We assess the short-term profile and timing stability of 22 millisecond pulsars that are part of the Parkes Pulsar Timing Array sample by examining intraobservation arrival time variability and single-pulse phenomenology. In 7 of the 22 pulsars, in the band centred at approximately 1400 MHz, we find that the brightest observations are limited by intrinsic jitter. We find consistent results, either detections or upper limits, for jitter noise in other frequency bands. PSR J1909−3744 shows the lowest levels of jitter noise, which we estimate to contribute ∼10 ns root mean square error to the arrival times for hour-duration observations. Larger levels of jitter noise are found in pulsars with wider pulses and distributions of pulse intensities. The jitter noise in PSR J0437−4715 decorrelates over a bandwidth of ∼2 GHz. We show that the uncertainties associated with timing pulsar models can be improved by including physically motivated jitter uncertainties. Pulse-shape variations will limit the timing precision at future, more sensitive, telescopes; it is imperative to account for this noise when designing instrumentation and timing campaigns for these facilities. [ABSTRACT FROM PUBLISHER]

S100 A9 belongs to the S100 family of calcium-binding proteins and plays a key role in many inflammatory conditions. Recent studies have found that S100 A9 was elevated significantly in the bronchoalveolar lavage fluid of idiopathic pulmonary fibrosis patients, and might be a biomarker for fibrotic interstitial lung diseases. However, the exact function of S100 A9 in pulmonary fibrosis needs further studies. We performed this study to investigate the effect of S100 A9 on human embryo lung fibroblast ( HLF) proliferation and production of cytokines and collagen, providing new insights into the possible mechanism. S100 A9 promoted proliferation of fibroblasts and up-regulated expression of both proinflammatory cytokines interleukin ( IL)-6, IL-8, IL-1β and collagen type III. S100 A9 also induced HLF cells to produce α-smooth muscle actin (α- SMA) and receptor for advanced glycation end-product ( RAGE). In addition, S100 A9 caused a significant increase in extracellular-regulated kinase ( ERK)1/2 mitogen-activated protein kinase ( MAPK) phosphorylation, while the status of p38 and c-Jun N-terminal kinase ( JNK) phosphorylation remained unchanged. Treatment of cells with S100 A9 also enhanced nuclear factor kappa B ( NF-κ B) activation. RAGE blocking antibody pretreatment inhibited the S100 A9-induced cell proliferation, cytokine production and pathway phosphorylation. S100 A9-mediated cell activation was suppressed significantly by ERK1/2 MAPK inhibitor and NF-κ B inhibitor. In conclusion, S100 A9 promoted HLF cell growth and induced cells to secret proinflammatory cytokines and collagen through RAGE signalling and activation of ERK1/2 MAPK and NF-κ B pathways. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) overexpression occurs in over 30% of esophageal carcinomas. Combination therapies of EGFR- and HER2-targeting agents with cytotoxic agents are considered a potential therapeutic strategy for esophageal cancer. The antitumor effects of lapatinib, a dual tyrosine kinase inhibitor of EGFR and HER2, cisplatin alone, and the combination of the two drugs on esophageal cancer cells were evaluated. The growth inhibition activity of lapatinib, cisplatin, and lapatinib plus cisplatin was measured by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assays, and the combination index values were calculated. Additionally, cell cycle distribution and cell apoptosis treated with lapatinib or cisplatin alone and the combination of the two drugs were detected by flow cytometry analysis. The activation of EGFR and HER2 signaling pathways was monitored by Western blot analysis. These experimental data showed that the combination of lapatinib and cisplatin synergistically inhibited cell proliferation and exhibited an enhanced pro-apoptotic effect on esophageal cancer cells. The underlying mechanisms of potentiated effects of combined treatment were associated with reduced phosphorylation of EGFR and HER2, and the downstream signaling molecules AKT and extracellular regulated protein kinases (ERK). Our findings indicated that the combination of lapatinib and cisplatin is one of the promising treatment strategies for esophageal carcinomas with EGFR and HER2 overexpression. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effect of Bacillus subtilis var. natto N21 (BAC) and Saccharomyces cerevisiae Y10 (SAC) fermented liquid feed (FLF) during different incubation times on the growth performance, relative organ weight, intestinal microflora, and organ antioxidative status in Landes geese. Two hundred forty male Landes geese (10 wk old) with the BW of 4.163 ± 0.108 kg were selected for a 3-wk trial and randomly allotted to 3 treatments according to their BW (10 replicates/treatment and 8 geese/replicate). The treatments included 1) CON, dry basal feed (corn-soybean basal diet mixed with water) before feeding (2:1 wt/wt), 2) FLF24, 24 h FLF, and 3) FLF48, 48 h FLF. The FLF diet was prepared by storing basal diet with 109 cfu/g feed of each BAC and SAC and water (2:1 wt/wt) in a closed tank at 20°C fermented for 24 or 48 h. The BW gain and feed intake of geese fed FLF24 and FLF48 was greater (P < 0.05) than CON treatment. Feeding geese with FLF24 and FLF48 feeds increased (P < 0.05) the relative weight of leg muscle whereas the liver was heavier (P < 0.05) in FLF48 treatment than CON and FLF24 treatments. The FLF24 and FLF48 increased (P < 0.05) the Lactobacillus population and depressed (P < 0.05) Escherichia coli population in small and large intestine. The high-density lipoprotein cholesterol concentration was greatest (P < 0.05) in FLF48 whereas the total cholesterol and low-density lipoprotein cholesterol was less (P < 0.05) in FLF24 and FLF48 treatments than CON. Geese fed FLF48 diet had greater glutathione peroxidase activity and less malondialdehyde content in heart and liver than those fed CON diet. In breast muscle, the superoxide dismutase activity were increased (P < 0.05) by FLF24 and FLF48 treatments than CON diet. In conclusion, the results indicated that feeding geese with BAC and SAC mix FLF can improve growth and feed intake, modulate the intestine ecology, and decrease the blood cholesterol concentrations; it also can improve the antioxidative status of organs and breast muscle. [ABSTRACT FROM AUTHOR]

Sorbic acid (SA) is a PUFA with a conjugated double bond. The conjugated fatty acids, including CLA, are multifunctional bioactive fatty acids with the ability to improve growth performance. The effect of SA on pig growth performance was examined to determine its mechanism of action. The ADG, ADFI, and serum IGF-I concentration were examined, as were IGF-I secretion and IGF system gene expression in hepatocytes. Two hundred forty 21-d-old Duroc × Landrace × Yorkshire weaned piglets (6.86 ±0.02 kg) were randomly divided into 4 groups, each consisting of 3 pens of 20 piglets (10 female and 10 male). The 4 groups of piglets were kept in a temperature-controlled room (26 to 28°C), and feed and water were provided to the pigs ad libitum. Weanling piglets were fed diets that included 0, 0.5, 2, or 4 g of SA/kg for 42 d. The diet supplemented with 0.5 g/kg of SA improved (P < 0.05) ADG, BW, and G:F, whereas supplementation with all 3 SA doses increased (P < 0.05) ADG and G:F at 21 to 42 d of age. The greatest concentration of plasma triglycerides was observed (P < 0.05) in the 4 g/kg of SA group. The SA increased (0.5 g of SA/kg, P > 0.05; 1 g of SA/kg, P < 0.05; and 2 g of SA/kg, P < 0.05, respectively) plasma total serum protein and globulin concentrations in a dose-dependent manner. It was noted that the smallest SA treatment dose (0.5 g/kg) dramatically increased (P < 0.05) serum IGF-I concentration but decreased (P < 0.05) the concentrations of blood urea N and cortisol. The SA increased (P < 0.05) IGF-I, IGF-II, IGF-I receptor (IGF-IR), and PPARa gene mRNA expression and IGF-I secretion, but not (P > 0.05) IGFBP or PPARγ mRNA expression, in pig primary hepatocytes. These results indicate that SA improves growth performance by regulating IGF system gene expression and hormone secretion. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although it has been recognized that Mycobacterium tuberculosis contains large amounts of Toll-like receptor 2 (TLR2) ligands, their direct effects on CD4(+) T cells and the clinical implications have not been determined. METHODS: With the recent finding that activated CD4(+) T cells express TLR2 as a costimulatory receptor, we hypothesized that M. tuberculosis and its components may directly affect CD4(+) T cells by engaging TLR2, thus facilitating the expansion and function of these lymphocytes in tuberculous pleura. RESULTS: Our results indicate that CD4(+) T cells from the pleural fluid and peripheral blood of patients with tuberculosis show significantly increased TLR2 expression, compared with those from healthy donors. TLR2 ligand activity was also significantly higher in the tuberculous pleural fluid than in the serum from healthy donors or patients with pulmonary tuberculosis. M. tuberculosis TLR2 ligands, 19-kDa lipoprotein, and live bacillus Calmette-Guérin all modulated cytokine production (interferon gamma and interleukin 17), cellular proliferation, survival, and migration of CD4(+) T cells isolated from pleural fluid and activated with anti-CD3 and anti-CD28. CONCLUSION: These data indicate that direct interaction between M. tuberculosis TLR2 ligands and CD4(+) T cells facilitated local CD4(+) T cell immune responses in patients with tuberculous pleurisy. Copyright © 2009 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Aims: To determine the effects of the ratios of hyaluronan synthase expression level to precursor sugar UDP-GlcA biosynthesis ability on the molecular weight (MW) of hyaluronic acid (HA) in recombinant Lactococcus lactis. Methods and Results: The genes sz HasA (hyaluronan synthase gene) and sz HasB (UDP-glucose-6-dehydrogenase gene) of Streptococcus zooepidemicus were introduced into L. lactis under the control of nisA promoter and lacA promoter respectively, resulting in a dual-plasmid controlled expression system. The effects of the ratios of hyaluronan synthase expression level to the precursor sugar UDP-GlcA biosynthesis ability under different induction concentration collocations with nisin and lactose on the MW of HA in recombinant L. lactis were determined. The results showed that the final weight-average molecular weight ( ) of HA correlated with the relative ratios of HasA (hyaluronan synthase) expression level to the concentration of UDP-GlcA. Conclusions: Regulating the relative ratios of HasA expression level to the precursor sugar biosynthesis ability was an efficient method to control the size of HA. Significance and Impact of the Study: This study put forward a guide to establish an efficacious way to control the size of HA in fermentation. [ABSTRACT FROM AUTHOR]

Extreme heat during certain clays of the summer renders pigs susceptible to severe heat stress, which negatively affects their growth performance. We hypothesized that such heat stress impaired the small intestinal mucosa, a site responsible for nutrient absorption. To simulate heat stress, Chinese experimental mini-pigs were treated with 5 h of continual 40°C temperature each clay for 10 d in succession. Pigs were killed at 1, 3, 6 and 10 d after treatment, and small intestinal epithelia were sampled for histochemical examination and biochemical analyses. The duodenum and jejunum were seriously damaged within 3 d of initiation of treatment. Subsequent study of the process of jejunum recovery showed that the initiation of recovery started within 6 d following heat stress. Such damage was associated with the downregulation of epithelial growth factor signaling. In conclusion, heat stress induced short-term damage to the epithehum of porcine intestine. Because the intestinal epitheliumn is crucial for nutrient uptake, such damage should partially account for the impairment of growth performance of pigs under heat stress. [ABSTRACT FROM AUTHOR]

Chloroplasts evolved as a result of endosymbiosis, during which sophisticated mechanisms evolved to translocate nucleus-encoded plastid-targeted enzymes into the chloroplast to form the chloroplast metabolic network. Given the constraints and complexity of endosymbiosis, will preferential attachment still be a plausible mechanism for chloroplast metabolic network evolution? We answer this question by analysing the metabolic network properties of the chloroplast and a cyanobacterium, Synechococcus sp. WH8102 (syw). First, we found that enzymes related to more ancient pathways are more connected, and synthetases have the highest connectivity. Most of the enzymes shared by the two densest cores between the chloroplast and syw are synthetases. Second, the highly conserved functional modules mainly consist of highly connected enzymes. Finally, isozymes and enzymes from endosymbiotic gene transfer (EGT) were distributed mainly in conserved modules and showed higher connectivity than nonisozymes or non-EGT enzymes. These results suggest that even with severe evolutionary constraints imposed by endosymbiosis, preferential attachment is still a plausible mechanism responsible for the evolution of the chloroplast metabolic network. However, the current analysis may not completely differentiate whether the chloroplast network properties reflect the evolution of the chloroplast network through preferential attachment or has been inherited from its cyanobacterial ancestor. To fully differentiate these two possibilities, further analyses of the metabolic network structure properties of organisms at various intermediate evolutionary stages between cyanobacteria and the chloroplast are needed. [ABSTRACT FROM AUTHOR]

Sphinganine-analog mycotoxins (SAMT) are polyketide-derived natural products produced by a number of plant pathogenic fungi and are among the most economically important mycotoxins. The toxins are structurally similar to sphinganine, a key intermediate in the biosynthesis of ceramides and sphingolipids, and competitive inhibitors for ceramide synthase. The inhibition of ceramide and sphingolipid biosynthesis is associated with several fatal diseases in domestic animals and esophageal cancer and neural tube defects in humans. SAMT contains a highly reduced, acyclic polyketide carbon backbone, which is assembled by a single module polyketide synthase. The biosynthesis of SAMT involves a unique polyketide chain-releasing mechanism, in which a pyridoxal 5′-phosphate-dependent enzyme catalyzes the termination, offloading and elongation of the polyketide chain. This leads to the introduction of a new carbon–carbon bond and an amino group to the polyketide chain. The mechanism is fundamentally different from the thioesterase/cyclase-catalyzed polyketide chain releasing found in bacterial and other fungal polyketide biosynthesis. Genetic data suggest that the ketosynthase domain of the polyketide synthase and the chain-releasing enzyme are important for controlling the final product structure. In addition, several post-polyketide modifications have to take place before SAMT become mature toxins. [ABSTRACT FROM AUTHOR]

Aims: The development and evaluation of a sensitive and specific TaqMan® real-time polymerase chain reaction (PCR) for the detection and identification of Pantoea stewartii on maize. Methods and Results: A TaqMan®-based real-time PCR assay targeting the cpsD gene enabling specific detection of P. stewartii in maize leaves and seeds was developed. Under optimal conditions, the selected primers and probe were specific for the detection of all 14 reference P. stewartii strains by real-time PCR. The 32 non- Panteoa and eight other Pantoea strains tested negative. The TaqMan® PCR assay detected 1 pg of purified DNA and 104 P. stewartii colony forming units per millilitre (10 cells per reaction) in pure cultures consisting of 92·0% intact (viable) cells. Direct processing of leaf lesions and seeds by the real-time PCR detected 10 and 50 P. stewartii cells per reaction respectively. TaqMan® real-time PCR results were validated by dilution plating of macerates and PCR-based subcloning followed by DNA sequencing. Conclusions: The real-time PCR assay described is a rapid, reliable and more sensitive tool for the detection of P. stewartii. Significance and Impact of the study: This real-time PCR assay would avoid false-negative results and reduce the time required for certifying maize seed shipments. [ABSTRACT FROM AUTHOR]

Background. Lack of circumcision has been identified as a risk factor for male genital human papillomavirus (HPV) infection, although this association has not been consistently supported. Methods. Specimens for HPV testing were collected from a cohort of 379 (primarily heterosexual) adult males. HPV prevalence in the glans penis and coronal sulcus, penile shaft, scrotum, semen, and urine was compared by circumcision status. Results. Overall, HPV DNA prevalence ranged from 6% in semen to 52% in the penile shaft. The prevalence of any HPV infection in the glans/corona was significantly higher in uncircumcised men (46%) than in circumcised men (29%) (odds ratio [OR], 1.96 [95% confidence interval {CI}, 1.02-3.75], adjusted for demographic characteristics and sexual history). Uncircumcised men also had an increased risk of oncogenic HPV infection (adjusted OR, 2.51 [95% CI, 1.11-5.69]) and infection with multiple HPV types (adjusted OR, 3.56 [95% CI, 1.50-8.50]). Among uncircumcised men, HPV prevalence in the foreskin (44%) was comparable to that in the glans/corona, and type-specific positivity was observed between the 2 sites (κ = 0.52). Conclusions. Uncircumcised men have an increased risk of HPV infection, including with oncogenic HPV, specifically localized to the glans/corona, possibly because of its proximity to the foreskin, which may be particularly vulnerable to infection. [ABSTRACT FROM AUTHOR]

Background Class I and class II HLA genes are thought to play a role in the immunopathogenesis of bullous dermatoses such as pemphigus vulgaris and pemphigus foliaceus, but we know little about the genetic background of paraneoplastic pemphigus (PNP) in Chinese patients. Objectives To identify class I and class II HLA alleles by genotyping in Chinese patients with PNP, and to find out the possible association between HLA alleles and disease susceptibility. Methods Nineteen Chinese patients with PNP were enrolled in this study. HLA-A, B, C, DRB1 and DQB1 alleles were typed by polymerase chain reaction and a colour-coded sequence-specific oligonucleotide probes method. Results The frequencies of HLA-B*4002/B*4004, B*51, B*52, Cw*14, DQB1*0301, DRB1*08 and DRB1*11 were relatively prevalent in Chinese Han patients with PNP in comparison with normal controls. After correction for multiple comparisons, Cw*14 remained statistically significant, and the other alleles were unremarkable in these patients. Conclusions The genetic background predisposing to PNP may be different in patients from various races and areas. HLA-Cw*14 may be the predisposing allele to PNP in Chinese patients, which is different from the predisposing allele in French patients with PNP and the alleles predisposing to pemphigus vulgaris and pemphigus foliaceus. [ABSTRACT FROM AUTHOR]

Aims: To study the physiology and metabolism of microbial cells in the performance of microbial fuel cells (MFCs). Methods and Results: A dual-chamber MFCs was constructed, and Rhodoferax ferrireducens was used as biocatalyst. To examine the physiology of microbial cells in the performance of MFCs, the anode media containing planktonic cells was replaced with fresh media in which KH2PO4 and/or NH4Cl were excluded. The replacing of anode media containing planktonic cells with fresh media excluded of KH2PO4 and NH4Cl made the coulombic yield remarkably increased by a factor of 68% (from 29·1 to 46·8C). The results showed that the electricity could be generated with cells in biofilms as biocatalyst, and coulombic yield was improved by limiting cell growth via removal of ingredients in anode media. By supplementation of glucose to the anode media when current declined to baseline, MFCs achieved about same platform current values immediately. MFCs could continue to produce electricity for about 30 h even after glucose was below detection. Conclusions: Biofilms and metabolism of glucose play important roles in the performance of MFCs. Coulombic yield of MFCs could be improved by regulating the media ingredients using the stable biofilms–electrode system. Significance and Impact of the Study: This is the first attempt to study the effect of ingredient compositions of anode media on the performance of MFCs. The observed results that MFCs continued to produce electricity after glucose was below detection was helpful to better understand the mechanism of microbial electricity production. [ABSTRACT FROM AUTHOR]

The genetic manipulation of the biosynthesis of fungal reduced polyketides has been challenging due to the lack of knowledge on the biosynthetic mechanism, the difficulties in the detection of the acyclic, non-aromatic metabolites, and the complexity in genetically manipulating filamentous fungi. Fumonisins are a group of economically important mycotoxins that contaminate maize-based food and feed products worldwide. Fumonisins contain a linear dimethylated C18 chain that is synthesized by Fum1p, which is a single module polyketide synthase (PKS). Using a genetic system that allows the specific manipulation of PKS domains in filamentous fungus Fusarium verticillioides, we replaced the KS domain of fumonisin FUM1 with the KS domain of T-toxin PKS1 from Cochliobolus heterostrophus. Although PKS1 synthesizes different polyketides, the F. verticillioides strain carrying the chimeric PKS produced fumonisins. This represents the first successful domain swapping in PKSs for fungal reduced polyketides and suggests that KS domain alone may not be sufficient to control the product’s structure. To further test if the whole fumonisin PKS could be functionally replaced by a PKS that has a similar domain architecture, we replaced entire FUM1 with PKS1. This strain did not produce any fumonisin or new metabolites, suggesting that the intrinsic interactions between the intact PKS and downstream enzymes in the biosynthetic pathway may play a role in the control of fungal reduced polyketides. [ABSTRACT FROM AUTHOR]

Paraneoplastic pemphigus (PNP) is an autoimmune mucocutaneous disease. We previously reported that B cells in a Castleman tumour associated with PNP produced autoantibodies. However, it is uncertain whether the production of autoantibodies from the associated tumour is a common mechanism in PNP. To investigate autoantibody production in a thymoma and a follicular dendritic cell sarcoma that were excised from two patients with PNP. Tumour cells were cultured, and their surface markers were identified. Indirect immunofluorescence, immunoblotting and enzyme-linked immunosorbent assay (ELISA) using culture media from the tumours were used to detect PNP autoantibodies. B cells with markers (CD22+, surface membrane IgG+ and surface membrane IgM+) of mature B lymphocytes constituted a proportion of cultured tumour cells in both tumours. Western blot showed that the medium from both the thymoma and the follicular dendritic cell sarcoma cells recognized 190-kDa periplakin and 210-kDa envoplakin bands of human epithelial proteins as well as recombinant linker regions of periplakin, envoplakin, desmoplakin and bullous pemphigoid antigen 1. ELISA was positive for antidesmoglein 3 antibody. The presence and localization in tumours of B-lymphocyte clones against proteins of the plakin family and desmoglein 3 in skin may not be confined to PNP with Castleman disease, but is possibly a common mechanism in PNP associated with various tumours. [ABSTRACT FROM AUTHOR]

Xeroderma pigmentosum (XP) is a group of autosomal recessive diseases characterized by hypersensitivity to ultraviolet rays. Among its eight complementation groups, XP group A (XPA) is the most severe type. The XPAC gene has been identified as the defective gene in XPA patients. To examine genomic DNA from a Chinese family with XPA, to determine the XPAC mutation and, after genetic counselling, to undertake DNA-based prenatal diagnosis in a subsequent pregnancy. Fetal DNA was extracted from amniotic fluid and used to amplify exon 5 of XPAC containing the potential mutation. Direct sequencing and restriction endonuclease digestion were used for prenatal diagnosis. We identified a homozygous nonsense XPAC mutation of 631C→T, which results in an R211X mutation in XPA protein, in the proband. Both her parents are heterozygous. Prenatal diagnosis demonstrated a heterozygous sequence predicting an unaffected child, and a healthy girl was born. These data provide the first example of a DNA-based prenatal test for genodermatosis in China. [ABSTRACT FROM AUTHOR]

Summary Background Familial benign chronic pemphigus or Hailey–Hailey disease (HHD; OMIM 169600) is an autosomal dominant blistering disease. Pathogenic mutations in ATP2C1 encoding a novel Ca[sup 2+] pump have recently been identified. Objectives To identify mutations in ATP2C1 in Chinese patients with HHD. Methods Eleven unrelated Chinese patients with HHD were subjected to mutation detection in ATP2C1 . Eight of them had a family history of HHD. The 27 coding exons and their flanking sequences were amplified and sequenced. Results Five of the 11 patients were identified to have heterozygous mutations including three nonsense mutations and two splicing mutations in ATP2C1 . Conclusions Four novel mutations, nonsense mutations S887X and W795X and splicing mutations 118-1 g→a and 1890+1del(gtgag)ins53, were found in this series of Chinese patients with HHD. [ABSTRACT FROM AUTHOR]

Shoot dieback, shoot growth, stem xylem cavitation, stem and root freezing injury, and root pressure were measured in 2-year-old, cold-hardened, potted yellow birch (Betula alleghaniensis Britt.) seedlings that had been subjected to a simulated winter thaw for 0, 5, 10, 19 or 27 days followed by 10 weeks at –10 °C. Stem xylem cavitation was determined as percent loss of hydraulic conductivity. Stem freezing injury was measured as electrolyte leakage (EL). Root freezing injury was determined by EL and by triphenyl tetrazolium chloride (TTC) reduction. Thaw duration was significantly correlated with dieback, new shoot growth, stem xylem cavitation, stem and root freezing damage, and root pressure (P < 0.05). In particular, shoot dieback was positively correlated with stem xylem cavitation (P < 0.001), residual stem xylem cavitation (P < 0.01) and root freezing injury (P < 0.010), but only weakly correlated with stem freezing damage (P < 0.05). In roots, freezing damage was negatively correlated with root pressure (P < 0.05), which, in turn, was negatively correlated with residual stem xylem cavitation after root pressure development. In stems, there was no correlation between freezing damage and xylem cavitation. We conclude that long periods of winter thaw followed by freezing resulted in freezing injury to roots concomitant with a reduction in root pressures, leading to poor recovery from freezing-induced xylem embolism. [ABSTRACT FROM PUBLISHER]

We have recently reported that systemic and chronic administration of recombinant tumour necrosis factor alpha (TNF-α), as well as streptococcal preparation (OK-432), inhibits development of insulin-dependent diabetes mellitus (IDDM) in NOD mice and BB rats, models of IDDM. In this study we examined whether serum containing endogenous TNF induced by OK-432 injection could inhibit IDDM in NOD mice. Treatment twice a week from 4 weeks of age with OK-432-injected mouse serum, which contained endogenous TNF (75U), but not IL-1, IL-2 and interferon-gamma (IFN-γ small gamma) activity, reduced the intensity of insulitis and significantly inhibited the cumulative incidence of diabetes by 28 weeks of age in NOD mice, as compared with the incidence in non-treated mice (P<0.01) and in mice treated with control serum (P<0.02), This inhibitory effect of the serum was diminished, although not significantly, by neutralization of serum TNF activity with anti-mouse TNF antibody. In the mice treated with the serum from OK-432-injected mice, Thy-1.2+ or CD8+ spleen cells decreased (P<0.01) and surface-Ig+ (S-Ig+) cells increased (P<0.05), whereas the proliferative response of spleen cells to concanavalin A (P<0.01) and lipopolysaccharide (P<0 05) increased. The results indicate that the inhibition by OK-432 treatment of IDDM in NOD mice was partially mediated by serum factors including endogenous TNF. [ABSTRACT FROM AUTHOR]

OBJECTIVE:: To characterize the structure of the parotid gland of the miniature pigs (minipig).Methods: Sialographic, anatomical, histological and ultrastructural studies of the parotid gland were performed on 11 minipigs.Results: Sialograms showed a long main duct and a triangular shaped gland. All branching ducts extended from the inferior-posterior margin of the main duct. No accessory glands were found. Typical serous acini were found microscopically and histochemically.Conclusion: This study provides basic structural information on the parotid gland of the minipig. [ABSTRACT FROM AUTHOR]

CD8+ T cells have been implicated in protective anti-tuberculous immune responses, but little is known about the identity of mycobacterial antigens recognized by CD8+ T cells. In this study we identified the Mycobacterium tuberculosis 38 kDa protein as a target for murine CD8+ cytotoxic T lymphocytes (CTL) which were induced by vaccination of C57BL/6 mice with DNA delivered with a plasmid, with transfected tumour cells or by infection with tubercle bacilli. Using overlapping synthetic peptides covering the whole protein sequence, peptides predicted to contain H-2Kb or H-2Db motifs, as well as naturally processed peptides, we were able to identify CTL epitopes. Differences were demonstrated in peptide specificity between CTL from immunized or M. tuberculosis-infected mice. The identified CTL epitopes could be important for future analysis of the involvement of CD8+ T cells in M. tuberculosis infections and for vaccine development. [ABSTRACT FROM AUTHOR]

The sign of Leser–Trélat (LT) is defined as the sudden eruption of multiple seborrhoeic keratoses (SKs), or increase in the number and size of existing SKs, associated with an underlying malignancy. A 75-year-old man was admitted to our hospital with dyspnoea and multiple verrucous papules that had been developing gradually over the previous 30 years. During the 3 months before presentation, the number of SKs on his chest and back had increased rapidly. A diagnosis of nasopharyngeal carcinoma was made based on results of computed tomography, endoscopy and biopsy examinations. The patient is receiving radiotherapy at present. To our knowledge, this is the first case of the Leser–Trélat sign associated with nasopharyngeal carcinoma. [ABSTRACT FROM AUTHOR]