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In the present work, we studied the structure-activity relationship (SAR) of tautomycetin (TMC) and its derivatives. Further, we demonstrated the correlation between the immunosuppressive fuction, anticancer activity and protein phosphatase type 1 (PP1) inhibition of TMC and its derivatives. We have prepared some TMC derivatives via combinatorial biosynthesis, isolation from fermentation broth or chemical degradation of TMC. We found that the immunosuppressive activity was correlated with anticancer activity for TMC and its analog compounds, indicating that TMC may home at the same targets for its immunosuppressive and anticancer activities. Interestingly, TMC-F1, TMC-D1 and TMC-D2 all retained significant, albeit reduced PP1 inhibitory activity compared to TMC. However, only TMC-D2 showed immunosuppressive and anticancer activities in studies carried out in cell lines. Moreover, TMC-Chain did not show any significant inhibitory activity towards PP1 but showed strong growth inhibitory effect. This observation implicates that the maleic anhydride moiety of TMC is critical for its phosphatase inhibitory activity whereas the C1-C18 moiety of TMC is essential for the inhibition of tumor cell proliferation. Furthermore, we measured in vivo phosphatase activities of PP1 in MCF-7 cell extracts treated with TMC and its related compounds, and the results indicate that the cytotoxicity of TMC doesn't correlate with its in vivo PP1 inhibition activity. Taken together, our study suggests that the immunosuppressive and anticancer activities of TMC are not due to the inhibition of PP1. Our results provide a novel insight for the elucidation of the underlying molecular mechanisms of TMC's important biological functions. [ABSTRACT FROM AUTHOR]

The article presents the findings of a research conducted on molecular cloning, gene expression, and functional characterization of palustrin-2CE, an antimicrobial peptide of rana chensinensis. Under the research, coding sequence corresponding to the mature palustrin-2CE peptide was subcloned into pCEX-6p-1. It concludes that the tadpole of the Chinese brown frog is a unique source of antimicrobial peptides and indicates the therapeutic potential of the palustrin- 2CE peptide.

Background: The Notch signaling pathway has been shown to be involved in the development of the nervous system. Recent studies showed that Notch receptors and ligands are also expressed in the nervous system of adult animals. However, whether the Notch signaling pathway has a function in adults is not fully understood. The present study is designed to investigate the function of the Notch signaling pathway in nociceptive transmission, especially during neuropathic pain in adult rats. Results: We found that the Notch intracellular domain (NICD) is expressed in the DRG (Dorsal Root Ganglia), sciatic nerve and spinal cord in normal rats, and is upregulated in the sciatic nerve and spinal cord after spared nerve injury (SNI). Moreover, we used the ?-secretase (a key enzyme of the Notch signaling pathway) inhibitor DAPT to observe the effect of the Notch signaling pathway after SNI. We found that intrathecal DAPT significantly increased paw withdrawal thermal latency and mechanical threshold. Mechanical hyperalgesia occurring after SNI could be significantly reversed by DAPT in a dose-dependent manner. Conclusions: These results suggest that the Notch signaling pathway participates in the induction and maintenance of neuropathic pain, which indicates that the Notch pathway maybe a potential drug target for neuropathic pain treatment. [ABSTRACT FROM AUTHOR]

The inability of epithelial cells from the cornea and other tissues to respond to LPS is reportedly due to low expression of the TLR4 co-receptor MD-2. We generated MD-2-/- bone marrow chimeras, and showed that MD-2 expression on non-myeloid cells was sufficient to mediate LPS-induced corneal inflammation. As IFN-γ is produced during Pseudomonas aeruginosa corneal infection, we examined the role of this cytokine on MD-2 expression by primary human corneal epithelial (HCE) cells and HCE cell lines. Exogenous IFN-γ was found to induce MD-2 mRNA, MD-2 cell surface expression, and LPS responsiveness as determined by p65 translocation to the nucleus and production of IL-6, CXCL1, and CXCL8/IL-8. Incubation with either the AG490 JAK2 inhibitor or with STAT1 siRNA blocked STAT1 phosphorylation and MD-2 transcription. Furthermore, EMSA analysis demonstrated that STAT1 binds to the MD-2 promoter, indicating that STAT1 is an MD-2 transcription factor. Together, these findings demonstrate that IFN-γ induces MD-2 expression and LPS responsiveness in HCE cells by JAK-2-dependent STAT1 activation and direct binding to the MD-2 promoter. Furthermore, given our findings on LPS-induced corneal inflammation, it is likely that IFN-γ-induced MD-2 expression by corneal epithelial cells contributes to the host response in vivo, determining the extent of tissue damage and bacterial clearance. [ABSTRACT FROM AUTHOR]

Based on grounded cognition theories, the current study showed that judgments about ability were regulated by the subjects' perceptions of their spatial height. In Experiment 1, we found that after seeing the ground from a higher rather than lower floor, people had higher expectations about their performance on a knowledge test and assigned themselves higher rank positions in a peer comparison evaluation. In Experiment 2, we examined the boundary conditions of the spatial height effects and showed that it could still occur even if we employed photos rather than actual building floors to manipulate the perceptions of spatial heights. In addition, Experiment 2 excluded processing style as an explanation for these observations. In Experiment 3, we investigated a potential mechanism for the spatial height effect by manipulating the scale direction in the questionnaire. Consequently, consistent with our representational dependence account, the effect of spatial heights on ability judgments was eliminated when the mental representation of ability was disturbed by a reverse physical representation. These results suggest that people's judgments about their ability are correlated with their spatial perception. [ABSTRACT FROM AUTHOR]

Arsenic, a curative agent for acute promyelocytic leukemia, induces cell apoptosis and degradation of BCR-ABL in chronic myelogenous leukemia (CML). We demonstrated that ubiquitination and degradation of BCR-ABL was mediated by c-CBL a RING-type E3 ligase that was also shown to be involved in ubiquitination for many other receptor/protein tyrosine kinases. Our data showed that c-CBL protein was considerably up-regulated by arsenic sulfide (As454). Interestingly, arsenic directly bound the RING finger domain of c-CBL to inhibit its self-ubiquitination/degradation without interfering with the enhancement of ubiquitination and subsequent proteolysis of its substrate BCR-ABL. Degradation of BCR-ABL due to c-CBL induction as a result of arsenic treatment was also observed in vivo in CML mice. These findings provide insight into the molecular mechanisms of arsenic and further support its therapeutic applications in CML in combination with tyrosine kinase inhibitors and potentially also in other malignancies involving aberrant receptor/protein tyrosine kinase signaling. [ABSTRACT FROM AUTHOR]

Detailed mechanistic studies on the palladium-catalyzed direct arylation of pyridine N-oxides are presented. The order of each reaction component is determined to provide a general mechanistic picture. The C—H bond cleaving step is examined in further detail through computational studies, and the calculated results are in support of an inner-sphere concerted metalation-deprotonation (CMD) pathway. Competition experiments were conducted with N-oxides of varying electronic characters, and results revealed an enhancement of rate when using a more electron-deficient species, which is in support of a CMD transition state. The effect of base on reaction rate was also examined and it was found that a carboxylate base was required for the reaction to proceed. This led to the conclusion that Pd(OAc)2 plays a pivotal role in the reaction mechanism as more than merely a precatalyst, but also as a source of acetate base required for the C—H bond cleavage step. [ABSTRACT FROM AUTHOR]

Di- and triphosphorylated small molecules represent key intermediates in a wide range of biological and chemical processes. The importance of polyphosphorylated species in biology and medicine underscores the need to develop methods for the detection and characterization of this compound class. We have reported two-dimensional HPP-COSY spectroseopy techniques to identify diphotphate-containing metabolic intermediates at submillimolar concentrations in the methylerythritol phosphate (MEP) isoprenoid biosynthetic pathway. In this work, we explore the scope of HPP-COSY-based techniques to characterize a diverse group of small organic molecules bearing di- and triphosphorylated moieties. These include molecules containing P-O-P and P-C-P connectivities, multivalent P(III)-O-P(V) phosphorus nuclei with widely separated chemical shifts, as well as virtually overlapping 31P resonances exhibiting strong coupling effects. We also demonstrate the utility of these experiments to rapidly distinguish between mono- and diphosphates. A detailed protocol for optimizing these experiments to achieve best performance is presented. [ABSTRACT FROM AUTHOR]

One hundred and eight isolates of Botrytis cinerea from greenhouse cucumber and tomato in two locations in Jiangsu Province (Nanjing and Huaiyin) and one location in Shandong Province were tested for their sensitivities to the four fungicides commonly used in China. Isolates with resistance to all four fungicides-carbendazim, diethofencarb, procymidone, and pyrimethanil (CarRDieRPrcRPyrR)-were found in all three regions in this study. High frequencies (52 and 53%) of resistance to all four fungicides were observed among the 62 isolates collected in Nanjing and the 36 isolates collected in Huaiyin in Jiangsu Province. The 10 isolates from Shandong Province were all resistant to the four fungicides. Pathogenicity and sporulation in vivo, and mycelial growth, sporulation, spore germination, and osmotic sensitivity to NaCI in vitro, were similar for the group of quadruple-resistant and wild-type isolates (P > 0.05). In the present study, the complete two-component histidine kinase gene (Bosi) was sequenced for 10 procymidone-resistant and 3 procymidone-sensitive B. cinerea isolates. Isolates representing four different procymidone-resistant phenotypes (CarRDieRPrcRPyrR, CarRDieRPrcRPyrR, CarRDieRPrcRPyrR, and CarRDieRPrcRPyrR) all had nucleic acid point mutations resulting in amino acid changes at position 369 (change from glutamine to proline) as well as at amino acid position 373 (asparagine to serine) in the Bosi gene. [ABSTRACT FROM AUTHOR]

The coupled ocean–atmosphere responses to idealized freshwater forcing in the western tropical Pacific are studied using a fully coupled climate model. The model explicitly demonstrates that freshwater forcing in the western tropical Pacific can lead to a basinwide response with the pattern resembling the Pacific decadal oscillation. In the tropics, a negative (positive) freshwater forcing over the western tropical Pacific decreases (increases) sea surface height locally, and sets up a positive (negative) zonal pressure gradient anomaly, which accelerates (decelerates) the meridional overturning circulation and equatorial surface westward flow. This leads to an intensification (reduction) of meridional heat divergence and vertical cold advection, and thus a development of La Niña (El Niño)–like responses in the tropics. The tropical responses are further substantiated by the positive Bjerknes feedback, and subsequently force significant changes in the extratropical North Pacific through atmospheric teleconnection. The local freshwater response also reinforces the imposed forcing, forming a positive feedback loop. Applications to Pacific climate changes are discussed. [ABSTRACT FROM AUTHOR]

In multimedia sensor networks, there may exist simultaneously two streams: end-to-end stream and event-to-sink stream. It brings a new set of challenges for QoS guarantees inmultimedia transmission. In this paper, we first present a self-adaptive QoS guarantee scheme based on two-layer feedback. In transport layer, we partition network into 10 typical states and design a transport protocol, which makes the state transition to the optimal one. Moreover, we design a revenue structure of media stream to describe the relation between QoS and multimedia capturing approaches in the application layer, thus evaluating the optimal scheme of capturing multimedia according to multimedia packet generation ratio calculated by transport layer. A series of simulation experiments using NS2 are performed to demonstrate the effectiveness of our proposed scheme. [ABSTRACT FROM AUTHOR]

Overactive bladder syndrome (OAB) is an idiopathic condition characterized by urinary urgency and urge incontinence. Detrusor overactivity has been traditionally described as the physiologic mechanism for OAB. However, the bladder urothehum (BU) may also be involved in the pathophysiology. This study measured polyamine signaling and its downstream effects on membrane conductivity in bladder urothelial cells (BUC) obtained from asymptomatic and OAB subjects. Immunohistofluorescence was used to measure ornithine decarboxylase (ODC) expression in BU. BUC, cultured from BU biopsies, were used for electrophysiologic studies. DL-α-Difluoromethylornithine (DFMO), spermine, or spermidine was used to modulate polyamine signaling in BUC. Results showed ODC overexpression in OAB BU. In OAB BUC, whole cell and cell-attached configuration showed significantly decreased currents. Using inside-out patches, outward currents increased significantly, suggesting a cytoplasmic source of the outward current block in OAB BUC. In control BUC, outward currents were mediated by the large-conductance calcium-activated potassium (BK) channel due to calcium dose-dependence and block by iberiotoxin. Spermidine and spermine blocked the outward current in normal BUC in dose-dependent fashion. Conversely, DFMO significantly increased (P < 0.01) outward currents in OAB BUC both in cell-attached and in whole cell configuration. The outward currents in DFMO-treated- OAB BUC could be significantly reduced (P < 0.05) by adding back spermidine and spermine. These data suggest that polyamine signaling is upregulated in OAB urothelium and OAB BUC. Furthermore, polyamines in BUC block the BK channel. Targeting of bladder urothehial polyamine signaling may represent a novel approach for OAB treatment based on pathophysiologic mechanisms. [ABSTRACT FROM AUTHOR]

Objective: This study aims to assess the impact of diabetes mellitus (DM) on the health-care utilization and clinical outcomes of patients with acute stroke. Methods: This is a retrospective cohort study. All patients who were admitted for the first time to one of the three public hospitals in the National Healthcare Group in Singapore from January 2005 to June 2007 with a primary diagnosis of acute stroke were included and were followed up for 1 year after the index hospitalization. The study population was divided into two groups: with DM and without DM. Both univariate and multivariate analyses were applied to compare the hospital length of stay (LOS), hospitalization costs, mortality, as well as the 1-year hospital readmissions between the DM and non-DM groups. Results: There were 9766 study patients, and 38.5% of them had DM. DM patients with ischemic stroke (IS) and transient ischemic attack (TIA) stayed 1-day and 0.6-day longer, and incurred 10% and 26% higher hospital cost during index admission, respectively, compared with their counterparts in the non-DM group. They also had more hospital readmission within 1 year. The mortality rate in IS patients with diabetes was 24% higher. After risk adjustment, subarachnoid hemorrhage patients with diabetes had more hospitalizations. Intracerebral hemorrhage (ICH) and IS patients in the DM group had all worse outcomes but the 1-year stroke recurrence; TIA patients with DM incurred longer LOS and hospital costs. Conclusion: DM predicts worse clinical outcomes and higher health-care expenditures in the 1-year poststroke especially for the IS, ICH, and TIA stroke subtypes. [ABSTRACT FROM AUTHOR]

The aims of this study were to determine optimal pacing parameters of electrical stimulation on different gut segments and to investigate effects and possible mechanisms of gastrointestinal electrical stimulation on gut slow waves. Twelve female hound-mix dogs were used in this study. A total of six pairs of electrodes were implanted on the stomach, duodenum, and ascending colon. Bilateral truncal vagotomy was performed in six of the dogs. One experiment was designed to study the effects of the pacing frequency on the entrainment of gut slow waves. Another experiment was designed to study the modulatory effects of the vagal and sympathetic pathways on gastrointestinal pacing. The frequency of slow waves was 4.88 ± 0.23 cpm (range, 4-6 cpm) in the stomach and 19.68 ± 0.31 cpm (range, 18-22 cpm) in the duodenum. There were no consistent or dominant frequencies of the slow waves in the colon. The optimal parameters to entrain slow waves were: frequency of 1.1 intrinsic frequency (IF; 10% higher than IF) and pulse width of 150-450 ms (mean, 320.0 ± 85.4 ms) for the stomach, and 1.1 IF and 10-20 ms for the small intestine. Electrical stimulation was not able to alter colon slow waves. The maximum entrainable frequency was 1.27 IF in the stomach and 1.21 IF in the duodenum. Gastrointestinal pacing was not blocked by vagotomy nor the application of an αor β-adrenergic receptor antagonist; whereas the induction of gastric dysrhythmia with electrical stimulation was completely blocked by the application of the aor 3-adrenergic receptor antagonist. Gastrointestinal pacing is achievable in the stomach and small intestine but not the colon, and the maximal entrainable frequency of the gastric and small intestinal slow waves is about 20% higher than the IF. The entrainment of slow waves with gastrointestinal pacing is not modulated by the vagal or sympathetic pathways, suggesting a purely peripheral or muscle effect. [ABSTRACT FROM AUTHOR]

A novel method based on solid-phase extraction was studied for the extraction of amitrole (3-amino-1,2,4-triazole), and its residue determination in apples has been developed. The samples were derivatized with 4-chloro-3,5-dinitrobenzotrifluoride (CNBF). The derivatization conditions and the influence of elution composition on the separation were investigated. In pH 9.5 H3BO3–Na2B4O7 media, the reaction of amitrole with CNBF was complete at 60°C after 30 min. The separation of derivatized amitrole was achieved at room temperature within 13 min by gradient elution mode with cetyltrimethylammonium bromide in mobile phase as ion-pair reagent. The method correlation coefficient was 0.9996, in concentrations ranging from 1.66 to 415 mg L−1. The calculated recoveries of the proposed method were from 94.17% to 105.67%, and relative standard deviations were 1.57% to 6.44% in the application to the quantitative determination of amitrole in apples. The detection limit of amitrole was 0.10 mg L−1 with a signal-to-noise ratio of 3. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Fusion between the membrane of HIV and the membrane of a host cell is a crucial step in HIV infection and is catalyzed by the binding of the fusion peptide domain (HFP) of the HIV gp41 protein to the host cell membrane. The HFP by itself induces vesicle fusion and is a useful model system to understand the fusion peptide/host cell membrane interaction. This article reports an experimental correlation between the membrane locations of different HFP constructs and their fusogenicities. The constructs were the HFP monomer with Val-2 to Glu-2 mutation (HFPmṉmut), wild type HFP monomer (HFPmn), and wild type HFP trimer (HFPtr). All constructs have predominant p sheet structure in membranes with physiologically relevant cholesterol content. HFPmṉmut does not fuse vesicles, HFPmn has moderate fusion rate, and HFPtr has the putative oligomerization state of HIV gp41 and a very rapid fusion rate. The HFP membrane locations were probed with solid-state NMR measurements of distances between labeled carbonyl (13C0) nuclei in the HFP backbone and lipid nuclei in the surface or interior regions of the membrane bilayer. HFPmṉmut is located at the membrane surface, HFPmn is inserted into a single membrane leaflet, and HFPtr is the most deeply inserted construct with contact with the center of the membrane. These results show a clear positive correlation between the insertion depths and the fusion activities of the HFP constructs. Other disease-causing enveloped viruses contain fusion peptides and this correlation may be a general structure-function model for these peptides. [ABSTRACT FROM AUTHOR]

Despite the abundance of iron in nature, it is the third most limiting nutrient for plants due to its minimal solubility in most soils. While certain soil microbes produce chelating agents that enhance the solubility of iron, the effectiveness of such siderophores in the assimilation of iron by plants is debated. With an increasing understanding that select soil microbes play a signaling role in activating growth and stress responses in plants, the question arises as to whether such symbionts regulate iron assimilation. Here we report a previously unidentified mechanism in which the growth-promoting bacterium Bacillus subtilis GB03 activates the plant’s own iron acquisition machinery to increase assimilation of metal ions in Arabidopsis. Mechanistic studies reveal that GB03 transcriptionally up-regulates the Fe-deficiency-induced transcription factor 1 ( FIT1), which is necessary for GB03-induction of ferric reductase FRO2 and the iron transporter IRT1. In addition, GB03 causes acidification of the rhizosphere by enhancing root proton release and by direct bacterial acidification, thereby facilitating iron mobility. As a result, GB03-exposed plants have elevated endogenous iron levels as well as increased photosynthetic capacity compared with water-treated controls. In contrast, loss-of-function fit1-2 mutants are compromised in terms of enhanced iron assimilation and photosynthetic efficiency triggered by GB03. In all studies reported herein, a physical partition separating roots from bacterial media precludes non-volatile microbial siderophores from contributing to GB03-stimulated iron acquisition. These results demonstrate the potential of microbes to control iron acquisition in plants and emphasize the sophisticated integration of microbial signaling in photosynthetic regulation. [ABSTRACT FROM AUTHOR]

Abstract  The adsorption amount of methane on 16 different kinds of materials at 3.5 MPa and 298 K holds a linear relation with the specific surface area. The linear relationship implies that gases are adsorbed monolayerly on the surface of adsorbents at above-critical temperatures. Determination of surface area and calculation of storage capacity of a material are explicitly discussed. It is indicated that methane storage is different from natural gas storage and the difference affects the development of storage material. Natural gas is a mixture and all components other than methane cannot be desorbed when the tank pressure released to atmospheric at ambient temperature, therefore, a storage mechanism other than adsorption might be more suitable. [ABSTRACT FROM AUTHOR]

A multitransition 3-mm molecular line single pointing and mapping survey was carried out towards 29 massive star-forming cores in order to search for the signature of inward motions. Up to seven different transitions, optically thick lines HCO+(1-0), CS(2-1), HNC(1-0), HCN(1-0) and 12CO(1-0), and optically thin lines C18O(1-0) and 13CO(1-0) were observed towards each source. The normalized velocity differences ( ) between the peak velocities of optically thick lines and optically thin line C18O(1-0) for each source were derived. Prominent inward motions are probably present in either HCO+(1-0) or CS(2-1) or HNC(1-0) observations in most sources. Our observations show that there is a significant difference in the incidence of blueshifted asymmetric line profiles between CS(2-1) and HCO+(1-0). The HCO+(1-0) shows the highest occurrence of obvious asymmetric features, perhaps owing to different optical depth between CS(2-1) and HCO+(1-0). HCO+(1-0) appears to be the best inward motion tracer. The mapping observations of multiple line transitions enable us to identify six strong infall candidates: G123.07-6.31, W75(OH), S235N, CEP-A, W3(OH) and NGC 7538. The infall signature is extended up to a linear scale . [ABSTRACT FROM AUTHOR]

Background: Chronic wound pathogenic biofilms are host-pathogen environments that colonize and exist as a cohabitation of many bacterial species. These bacterial populations cooperate to promote their own survival and the chronic nature of the infection. Few studies have performed extensive surveys of the bacterial populations that occur within different types of chronic wound biofilms. The use of 3 separate 16S-based molecular amplifications followed by pyrosequencing, shotgun Sanger sequencing, and denaturing gradient gel electrophoresis were utilized to survey the major populations of bacteria that occur in the pathogenic biofilms of three types of chronic wound types: diabetic foot ulcers (D), venous leg ulcers (V), and pressure ulcers (P). Results: There are specific major populations of bacteria that were evident in the biofilms of all chronic wound types, including Staphylococcus, Pseudomonas, Peptoniphilus, Enterobacter, Stenotrophomonas, Finegoldia, and Serratia spp. Each of the wound types reveals marked differences in bacterial populations, such as pressure ulcers in which 62% of the populations were identified as obligate anaerobes. There were also populations of bacteria that were identified but not recognized as wound pathogens, such as Abiotrophia para-adiacens and Rhodopseudomonas spp. Results of molecular analyses were also compared to those obtained using traditional culture-based diagnostics. Only in one wound type did culture methods correctly identify the primary bacterial population indicating the need for improved diagnostic methods. Conclusion: If clinicians can gain a better understanding of the wound's microbiota, it will give them a greater understanding of the wound's ecology and will allow them to better manage healing of the wound improving the prognosis of patients. This research highlights the necessity to begin evaluating, studying, and treating chronic wound pathogenic biofilms as multi-species entities in order to improve the outcomes of patients. This survey will also foster the pioneering and development of new molecular diagnostic tools, which can be used to identify the community compositions of chronic wound pathogenic biofilms and other medical biofilm infections. [ABSTRACT FROM AUTHOR]

Aminopeptidase N (APN, CD13; EC 3.4.11.2) is a transmembrane metalloprotease with several functions, depending on the cell type and tissue environment. In tumor vasculature, APN is overexpressed in the endothelium and promotes angiogenesis. However, there have been no reports of in vivo inactivation of the APN gene to validate these findings. Here we evaluated, by targeted disruption of the APN gene, whether APN participates in blood vessel formation and function under normal conditions. Surprisingly, APN-null mice developed with no gross or histological abnormalities. Standard neurological, cardiovascular, metabolic, locomotor, and hematological studies revealed no alterations. Nonetheless, in oxygen-induced retinopathy experiments, APN-deficient mice had a marked and dose-dependent deficiency of the expected retinal neovascularization. Moreover, gelfoams embedded with growth factors failed to induce functional blood vessel formation in APN-null mice. These findings establish that APN-null mice develop normally without physiological alterations and can undergo physiological angiogenesis but show a severely impaired angiogenic response under pathological conditions. Finally, in addition to vascular biology research, APN-null mice may be useful reagents in other medical fields such as malignant, cardiovascular, immunological, or infectious diseases. [ABSTRACT FROM AUTHOR]

Background: Although many genomic features have been used in the prediction of protein-protein interactions (PPIs), frequently only one is used in a computational method. After realizing the limited power in the prediction using only one genomic feature, investigators are now moving toward integration. So far, there have been few integration studies for PPI prediction; one failed to yield appreciable improvement of prediction and the others did not conduct performance comparison. It remains unclear whether an integration of multiple genomic features can improve the PPI prediction and, if it can, how to integrate these features. Results: In this study, we first performed a systematic evaluation on the PPI prediction in Escherichia coli (E. coli) by four genomic context based methods: the phylogenetic profile method, the gene cluster method, the gene fusion method, and the gene neighbor method. The number of predicted PPIs and the average degree in the predicted PPI networks varied greatly among the four methods. Further, no method outperformed the others when we tested using three well-defined positive datasets from the KEGG, EcoCyc, and DIP databases. Based on these comparisons, we developed a novel integrated method, named InPrePPI. InPrePPI first normalizes the AC value (an integrated value of the accuracy and coverage) of each method using three positive datasets, then calculates a weight for each method, and finally uses the weight to calculate an integrated score for each protein pair predicted by the four genomic context based methods. We demonstrate that InPrePPI outperforms each of the four individual methods and, in general, the other two existing integrated methods: the joint observation method and the integrated prediction method in STRING. These four methods and InPrePPI are implemented in a user-friendly web interface. Conclusion: This study evaluated the PPI prediction by four genomic context based methods, and presents an integrated evaluation method that shows better performance in E. coli. [ABSTRACT FROM AUTHOR]

Interstitial cystitis (IC) is an idiopathic condition characterized by bladder hyperalgesia. Studies have shown cytokine and purinergic signaling abnormalities in cultured bladder urothelial cells (BUC) from IC patients. We performed single-cell electrophysiological studies in both normal and IC BUC. A strongly inward rectifying potassium current with conductance of the Kir2.1 channel was identified in normal BUC. This current was significantly reduced in IC BUC. Kir2.1 protein and mRNA were detected in both IC and normal BUC. Epidermal growth factor (EGF) caused a dose-dependent decrease in the inward potassium current in normal BUC. EGF is secreted in higher amounts by IC BUC and is known to decrease Kir2.1 conductance by phosphorylation of Kir2.1. Genistein, a nonspecific phosphorylation inhibitor, increased the inward potassium current in IC BUC and blocked the effect of EGF on normal BUC. Treatment of IC BUC with heparin-binding epidermal growth factor-like growth factor (HB-EGF), previously shown to be secreted in lower amounts by IC BUC, significantly increased inward potassium current. These data show that the inward potassium current in BUC can be modulated by EGF and HB-EGF. Changes in BUC membrane potassium conductance caused by altered levels of EGF and HB-EGF may therefore play a role in the pathophysiology of IC. [ABSTRACT FROM AUTHOR]

The establishment of the Yan state by the Zhou court during late eleventh century BCE had fulfilled the attempt by the dynastic power to colonize and control the local population of northern Hebei. The Yan and the two local groups, one active in the Yan mountainous region and the other in the Jing, Jin, and Tang area, developed a cooperative relationship during the early Western Zhou period. The cooperation between Yan and local elites was mutually beneficial. While local elite culture was heavily influenced by that of the Shang and Zhou, local traditions continued to be present. [ABSTRACT FROM AUTHOR]

Interstitial cystitis (IC) is an idiopathic hypersensory condition of the bladder associated with increased urinary ATP and increased stretch-activated ATP release by bladder urothelial cells (BUCs), suggesting augmented purinergic signaling in the bladder. To test this theory further, monolayers of cultured BUCs derived from bladder biopsies obtained from patients with IC and control patients were stimulated with 10-30 µM ATP with subsequent measurement of extracellular ATP levels using the luciferin-luciferase assay. Stimulation with 30 µM ATP resulted in IC supernatant containing several-fold more ATP than control BUCs initially, followed by a slower decrease in ATP levels. This difference in ATP levels was not completely due to activity of cellular ecto-ATPase, because blockade with ARL67 156 did not normalize the difference. Exposure to hypotonic solutions resulted in similar extracellular ATP concentrations in IC and control BUCs, but there Was a slower decrease in ATP levels in IC supernatants. Treatment of IC BUCs with 10-40 µM suramin, a nonspecific P2 receptor antagonist, significantly attenuated the IC BUC response to extracellular ATP, restoring IC BUCs to a control phenotype. Pre- treatment of IC BUCs with 20 ng/ml of heparin-binding EGF-like growth factor (HB-EGF), which previously has been shown to be decreased in IC urine specimens, also restored IC BUCs to a control phenotype with respect to response to ATP stimulation. In conclusion, IC BUCs have augmented extracellular ATP signaling that could be blocked by suramin and HB-EGF. These findings suggest the possible development of future novel therapeutic techniques. [ABSTRACT FROM AUTHOR]

Reports on the recognition of corruption as the major factor undermining transitions to market economies in China. Details on the neoliberal logic that economic liberalization can reduce bureaucratic intervention, open up competition, and bring out free markets; Accounts on the development role of the central government over infrastructure, waterworks, poverty reduction and rural relocation; Characteristics of the dominant patterns of Chinese corruption.

This paper presents a data-loading technique that jointly considers the effect of channel estimation and the property of encoded multimedia dab in Orthogonal Frequency Division Multiplexing (OFDM) systems. We observe that OFDM sub-channels experience different average bit error rate (BER) due to channel estimation inaccuracy. The leakage effect in the fast Fourier transform (FFT)-based channel estimation method or the model mismatch in the polynomial-based channel estimation method results in a variation on the decoded BER across different OFDM subchannels. Thus, we are motivated to design the Priority Transmission (PT) scheme, which utilizes this BER variation across different OFDM subchannels and provides unequal error protection (UEP) for multimedia transmission. In addition, since OFDM has been adopted in many multimedia transmission standards, we compare the different channel estimation techniques, which were compared only for generic data transmission before, in the context of multimedia transmission with the PT scheme. In particular, we extend the polynomial-based channel estimation that was previously designed for a decision-directed scenario to a pilot-symbol-assisted (PSA) channel estimation scenario. Then, we Investigate the channel estimation mean square error (MSE) and BER performance of individual OFDM subchannels for both the FFT-based and the polynomial-based channel estimation. Furthermore, we design the PT scheme that achieves significant gain in peak-signal-to-noise ratio (PSNR) of the reconstructed images for both channel estimation methods. Finally, we compare different OFDM channel estimation techniques for multimedia transmission. It is shown that for generic data transmission, the polynomial-based PSA channel estimation outperforms the FFT-based method in realistic channel conditions, and both types of channel estimation have similar performance when using the proposed PT scheme for multimedia transmission. [ABSTRACT FROM AUTHOR]

Our current understanding of the role of phytohormones in the development of cotton fibers is derived largely from an amenable culture system in which cotton ovules, collected on the day of anthesis, are floated on liquid media. Under these conditions, supplemental auxin and gibberellin were found to promote fiber initiation and elongation. More recently, addition of low concentrations of the brassinosteroid brassinolide (BL) were also found to promote fiber elongation while a brassinosteroid biosynthesis inhibitor brassinazole2001 (Brz) inhibited fiber development. In order to elucidate the role of brassinosteroid in cotton fiber development further, we have performed a more detailed analysis of the effects of these chemicals on cultured cotton ovules. Our results confirm that exogenous BL promotes fiber elongation while treatment with Brz inhibits it. Furthermore, treatment of cotton floral buds with Brz results in the complete absence of fiber differentiation, indicating that BR is required for fiber initiation as well as elongation. Expression of fiber genes associated with cell elongation increased in ovules treated with BL and was suppressed by Brz treatment, establishing a correlation between brassinosteroid-regulated gene expression and fiber elongation. These results establish a clear connection between brassinosteroid and fiber development and open the door for genetic analysis of cotton development through direct modification of the brassinosteroid signal transduction pathway. [ABSTRACT FROM AUTHOR]

Dual vectors are applied in Hamilton system of applied mechanics. Electric and magnetic field vectors are the dual vectors in electromagnetic field. The Hamilton system method is introduced into the analysis of electromagnetism waveguide with inhomogeneous materials. The transverse electric and magnetic fields are regarded as the dual. The basic equations are solved in Hamilton system and symplectic geometry. With the Hamilton variational principle, the symplectic semi-analytical equations are derived and preserve their symplectic structures. The given numerical example demonstrates the solution of LSE (Longitudinal Section Electric) mode in a dielectric waveguide. [ABSTRACT FROM AUTHOR]

Contingency analysis (CA) is critical in many routine power system and market analyzes to show potential problems with the system. Due to the tremendous and yet increasing amount of data computed by CA, effective visualizations are needed to present the CA results to assist the system operators and engineers to comprehend the static security status of the system in a quick and intuitive manner. The desirable functionalities of such visualizations include showing the overall system security status, showing the severity levels of the contingencies in terms of their associated limit violations, and showing the geographic connection between the violated elements and the contingent elements. The traditional EMS display of CA results is a tabe War list of elements with limit violations. This paper explores interactive three-dimensional visualizations for contingency data. We visualize vulnerability levels of power system elements and severity information of outages separately. The overall situation of the whole system is conveyed "at a glance" by the overview visualizations, while more detailed information is displayed as needed. [ABSTRACT FROM AUTHOR]

Background: Many arrhythmias are triggered by abnormal electrical activity at the ionic channel and cell level, and then evolve spatio-temporally within the heart. To understand arrhythmias better and to diagnose them more precisely by their ECG waveforms, a whole-heart model is required to explore the association between the massively parallel activities at the channel/cell level and the integrative electrophysiological phenomena at organ level. Methods: We have developed a method to build large-scale electrophysiological models by using extended cellular automata, and to run such models on a cluster of shared memory machines. We describe here the method, including the extension of a language-based cellular automaton to implement quantitative computing, the building of a whole-heart model with Visible Human Project data, the parallelization of the model on a cluster of shared memory computers with OpenMP and MPI hybrid programming, and a simulation algorithm that links cellular activity with the ECG. Results: We demonstrate that electrical activities at channel, cell, and organ levels can be traced and captured conveniently in our extended cellular automaton system. Examples of some ECG waveforms simulated with a 2-D slice are given to support the ECG simulation algorithm. A performance evaluation of the 3-D model on a four-node cluster is also given. Conclusions: Quantitative multicellular modeling with extended cellular automata is a highly efficient and widely applicable method to weave experimental data at different levels into computational models. This process can be used to investigate complex and collective biological activities that can be described neither by their governing differentiation equations nor by discrete parallel computation. Transparent cluster computing is a convenient and effective method to make time-consuming simulation feasible. Arrhythmias, as a typical case, can be effectively simulated with the methods described. [ABSTRACT FROM AUTHOR]

Examines the association of SH2 domain-containing phosphatase 1 (SHP-1) with angiotensin II receptor AT[sub 2]. Role of G[sub Βγ] in the association process; Factors facilitating signal transduction for G protein-coupled receptors; Paradigm for the activation of SHP-1/2-class tyrosine phosphatases by G protein-coupled receptors.

Analyzes the online detection of a very long and weak chirp signal and studied the performance of the Hough transform detector. Challenges to the detection of linear frequency modulated signals; Information on the Hough transform detector; Description of the minimum detectable frequency slope.

Recently, the effects of weed control on crop yield, quality and soil fertility have been increasingly investigated. However, soil microorganism diversity under weed control, especially for aromatic plants, is little studied. Mechanical weeding effects on soil fertility and microbial diversity in star anise plantations remain unknown, limiting improvements in crop quality and yield through weed control. Therefore, mechanical weeding (MW) and no weeding (NW) zones were randomly designed in the same star anise plantation to study the mechanical weeding impacts on soil biological properties and microbial diversity. The phosphatase activity of MW soil was significantly higher than that of NW soil; however, aminopeptidase activity was significantly lower than that under NW. There was no significant difference in ß-glucosidase activity between MWand NW. Moreover, soil microbial biomass C and N inMWsoil were significantly higher than those of NW, but soil microbial biomass P was significantly lower than that of NW. Proteobacteria, Acidobacteria, Actinobacteria, Chloroflexi, Planctomycetes, WPS-2, Firmicutes and Verrucomicrobia were the predominant bacterial phyla inMW and NW soils. Specifically, Bacteroidetes was enriched inMW soil, being the unique dominant bacteria. Ascomycota, Basidiomycota, unclassified_k_-Fungi, Rozellomycota and Mortierellomycota were the predominant fungi inMW and NW soils. The numbers of dominant bacterial genera (> 1%) were 26 and 23 for NW andMW soils, respectively. Among them, norank_f__norank_o__norank_c__Subgroup_6, 1921-2 and norank_f__norank_o__B12-WMSP1 went undetected inMWsoil. Moreover, the numbers of dominant fungi in soils of star anise plantations were 11 and 9 for NW and MW, respectively. Among them, only unclassified_f__Clavicipitaceae and Mortierella went undetected inMWsoils. Thus, soil microbial community structures are not significantly altered by mechanical weeding. The above results suggest that soil fertility can be improved and soil heath can be maintained by mechanical weeding in star anise plantations. Moreover, soilborne diseases maybe easily occurred under NW treatment in star anise plantation. [ABSTRACT FROM AUTHOR]

The altered expression of microRNAs (miRNAs) is associated with a number of cancer types. The study of the association between the miRNA profile and cancer may be useful to identify potential biomarkers of certain types of cancer. In the present study, 19 miRNAs were identified by high-throughput sequencing in the serum of colorectal cancer (CRC) patients. A network analysis was performed based on a computational approach to identify associations between CRC and miRNAs. The present study may be useful to identify cancer-specific signatures and potentially useful biomarkers for the diagnosis of CRC. The network analysis of miRNA-target genes may aid in identifying altered miRNA regulatory networks that are involved in tumor pathogenesis. [ABSTRACT FROM AUTHOR]

C16H30O5, monoclinic, P21 (no. 4), a = 5.6814(5) Å, b = 13.0181(12) Å, c = 22.833(2) Å, β = 96.473(2)°, V = 1677.9(3) Å3, Z = 4, Rgt(F) = 0.0508, wRref(F2) = 0.1346, T = 296(2) K. [ABSTRACT FROM AUTHOR]

Energy levels, radiative rates, lifetimes, hyperfine structures and Landé gJ -factors for electric-dipole (E1), electric-quadrupole (E2), magnetic-dipole (M1), and magnetic-quadrupole (M2) transitions among the lowest 41 levels belonging to the n = 3 states (1s²2s²2p6)3s²3p³, 3s³p4, and 3s²3p²3d in Rb(XXIII) are calculated through the multiconfiguration Dirac-Hartree-Fock method. High-accuracy calculations have been performed as benchmarks in the request for accurate treatments of relativity, electron correlation, and quantum electrodynamic effects in multi-valence-electron systems. The calculated energy levels are in excellent agreement with the experimental results and the theoretical ones, wherever available. The calculated values including core-valence correction are found to be in good agreement with other theoretical and experimental values. The present results are reported as benchmarks for future calculations and measurements. [ABSTRACT FROM AUTHOR]

Abstract: The effect of exchange-coupling interaction on domain pinning mechanism in nanometer permanent materials has been investigated using random anisotropy model. Exchange-coupling coefficient α ex has been studied, and α ex corresponding to pinning fields is derived from coercivity formula, which is expressed as . Our results show that α ex is related with the degree of exchange-coupling interaction and properties of grain boundary. Coercivity decreases with the increasing degree of exchange-coupling interaction. Our results are accordant with other relative theoretical results. In order to obtain higher coercivity, exchange-coupling interaction between magnetically hard–hard grains should be weakened. [Copyright &y& Elsevier]

The title compound, C19H18F2IO6P, prepared as a potential antiviral and anticancer agent from 3-methylsalicylchlorophosphane and 1-(2,4-difluoro-5-iodophenyl)-2-deoxy-β-D-ribofuranose, is one of a 1:1 mixture of two diastereomers. The diastereomers differ in their configuration, S or R, at the asymmetric phosphorus center. X-Ray crystallographic analysis of the title compound has determined the absolute configuration at the asymmetric P center to be S. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) accounts for ~20% of all breast cancer (BC) cases. The management of TNBC represents a challenge due to its worse prognosis, heterogeneity and lack of targeted therapy. Moreover, its mechanisms are not fully clear. The aim of the study is to identify crucial genes between TNBC and non-TNBC for underlying targets for diagnostic and therapeutic methods of TNBC. The differentially expressed genes (DEGs) between TNBC and non-TNBC were selected from the Gene Expression Omnibus (GEO) database after the integrated analysis of two datasets (GSE65194 and GSE76124). Then Gene ontology (GO) and KEGG analysiswere performed by DAVID database, protein-protein interaction (PPI) of DEGs was constructed by Search Tool for the Retrieval of Reciprocity Genes (STRING) database. Furthermore, centrality analysis and module analysis were carried out by Cytoscape to analyze the TNBC-related PPI. Subsequently, overall survival (OS) analysis was performed by GEPIA. Finally, the expressions of these key genes in TNBC and non-TNBC tissues were tested by qRT-PCR. The results showed that 955 DEGs were obtained, which were mainly enriched in ribosome, ribosomal subunit, and so on. Moreover, 19 candidate genes were focused on by centrality analysis and module analysis. Furthermore, we found the low expressions of ribosomal protein S9 (RPS9), ribosomal protein S14 (RPS14), ribosomal protein S27 (RPS27), ribosomal protein L11 (RPL11) and ribosomal protein L14 (RPL14) were related to a poor OS in BC patients. Additionally, qRT-PCR results suggested that these five genes were notably down-regulated in TNBC tissues. In summary, the present study suggests that ribosomal proteins are related to TNBC, and they may play an important role in the diagnosis, treatment and prognosis of TNBC. [ABSTRACT FROM AUTHOR]

Background: Obesity is a principal risk factor for the development of type 2 diabetes and cardiovascular diseases. Natural plants and/or foods play an important role in the management of obesity. Acalypha australis L. (AAL) is a kind of potherb popular among Asian populations, and it is also consumed as a food ingredient and traditional herbal medicine. Objective: We investigated the effects of water extract from AAL on high-fat-diet (HFD)-induced obese mice and 3T3-L1 adipocytes to develop a new functional food material. Design: Nine-week-old male mice were randomly divided into control (chow diet, n = 6) and HFD (n = 30) group. From 12-weeks onward, mice in the HFD group were further separated into model (saline, 6 mL/kg), simvastatin (0.11 mg/mL, 6 mL/kg), and AAL treatment (low, middle, and high dosage: 300, 600, and 900 mg/kg) group, with 6 animals per group, while mice in the control group were treated with saline (6 mL/ kg). Food intake, body/fat weight, liver/kidney indexes, and lipid profiles were determined. Tissues were fixed with formalin for pathological examination. Western blotting and PCR were performed to evaluate the protein and mRNA expression in 3T3-L1 adipocytes. Oil Red O staining was used to determine lipid accumulation. Results: AAL administration significantly suppressed body weight gain, and reduced fat pad weight and Lee's index in obese mice, but had no effect on liver/kidney index. AAL also reduced serum cholesterol, triglyceride, and LDL-C and increased HDL-C levels. Histological analysis revealed that AAL significantly ameliorated lipid accumulation in the liver and subcutaneous adipose tissue. In vitro, Oil Red O staining showed that AAL inhibited adipose differentiation by down-regulating the gene and protein expression of PPARγ and C/EBPα. AAL also reversed HFD-induced intestinal dysbacteriosis. Conclusion: AAL water-soluble extract has a significant anti-adipogenic effect in the HFD-induced obese mice model. [ABSTRACT FROM AUTHOR]

The time of day strongly influences adaptive behaviors like long-term memory, but the correlating synaptic and molecular mechanisms remain unclear. The circadian clock comprises a canonical transcription-translation feedback loop (TTFL) strictly dependent on the BMAL1 transcription factor. We report that BMAL1 rhythmically localizes to hippocampal synapses in a manner dependent on its phosphorylation at Ser42 [pBMAL1(S42)]. pBMAL1(S42) regulates the autophosphorylation of synaptic CaMKIIa and circadian rhythms of CaMKIIa-dependent molecular interactions and LTP but not global rest/activity behavior. Therefore, our results suggest a model in which repurposing of the clock protein BMAL1 to synapses locally gates the circadian timing of plasticity. [ABSTRACT FROM AUTHOR]

We present the results of a single dish interstellar maser survey toward ∼200 molecular clouds (MCs) in the extreme outer Galaxy (EOG) possibly lying in the Outer Scutum-Centaurus (OSC) arm. The observations resulted in the detections of two new 22.2 GHz water masers, two new 6.7 GHz class II methanol masers, and one new 4765 MHz excited-state OH maser. These new detections include one high Galactic latitude (b > 2°) methanol maser, one farthest Galactic methanol maser, and one farthest Galactic OH maser from the Sun. The velocities of the masers and the CO emission are in agreement with each other, which strongly indicates an association between the maser and the EOG cloud. The presence of the masers provides reliable evidence for ongoing massive star-forming activity in the OSC arm. The EOG clouds with detected interstellar masers are all associated with young stellar objects. Masers are primarily detected toward the brighter and more massive MCs. Because of the large distances involved, the “faint” masers with luminosity below 10−6L☉ are not accessible by our current observations. The low number of masers in the EOG regions supports the scenario of decreasing metallicity and decreasing star formation rate/efficiency at large Galactocentric radii. Our new maser detections are valuable targets for future VLBI parallax and proper motion measurements. [ABSTRACT FROM AUTHOR]

In 2-dimensional systems at finite temperature, long-wavelength Mermin-Wagner fluctuations prevent the existence of translational long-range order. Their dynamical signature, which is the divergence of the vibrational amplitude with the system size, also affects disordered solids, and it washes out the transient solid-like response generally exhibited by liquids cooled below their melting temperatures. Through a combined numerical and experimental investigation, here we show that long-wavelength fluctuations are also relevant at high temperature, where the liquid dynamics do not reveal a transient solid-like response. In this regime, these fluctuations induce an unusual but ubiquitous decoupling between long-time diffusion coefficient D and structural relaxation time τ, where D∝τ-κ, with κ>1. Long-wavelength fluctuations have a negligible influence on the relaxation dynamics only at extremely high temperatures in molecular liquids or at extremely low densities in colloidal systems. [ABSTRACT FROM AUTHOR]

Pharmacological studies have indirectly shown that necroptosis participates in ischemic neuronal death. However, its mechanism has yet to be elucidated in the ischemic brain. TNFα-triggered RIPK1 kinase activation could initiate RIPK3/MLKL-mediated necroptosis under inhibition of caspase-8. In the present study, we performed middle cerebral artery occlusion (MCAO) to induce cerebral ischemia in rats and used immunoblotting and immunostaining combined with pharmacological analysis to study the mechanism of necroptosis in ischemic brains. In the ipsilateral hemisphere, we found that ischemia induced the increase of (i) RIPK1 phosphorylation at the Ser166 residue (p-RIPK1), representing active RIPK1 kinase and (ii) the number of cells that were double stained with P-RIPK1 (Ser166) (p-RIPK1+) and TUNEL, a label of DNA double-strand breaks, indicating cell death. Furthermore, ischemia induced activation of downstream signaling factors of RIPK1, RIPK3 and MLKL, as well as the formation of mature interleukin-1β (IL-1β). Treatment with necrostatin-1 (Nec-1), an inhibitor of necroptosis, significantly decreased ischemia-induced increase of p-RIPK1 expression and p-RIPK1+ neurons, which showed protection from brain damage. Meanwhile, Nec-1 reduced RIPK3, MLKL and p-MLKL expression levels and mature IL-1β formation in Nec-1 treated ischemic brains. Our results clearly demonstrated that phosphorylation of RIPK1 at the Ser166 residue was involved in the pathogenesis of necroptosis in the brains after ischemic injury. Nec-1 treatment protected brains against ischemic necroptosis by reducing the activation of RIPK1 and inhibiting its downstream signaling pathways. These results provide direct in vivo evidence that phosphorylated RIPK1 (Ser 166) plays an important role in the initiation of RIPK3/MLKL-dependent necroptosis in the pathogenesis of ischemic stroke in the rodent brain. [ABSTRACT FROM AUTHOR]

Antibiotics are among the most used weapons in fighting microbial infections and have greatly improved the quality of human life. However, bacteria can eventually evolve to exhibit antibiotic resistance to almost all prescribed antibiotic drugs. Photodynamic therapy (PDT) develops little antibiotic resistance and has become a promising strategy in fighting bacterial infection. To augment the killing effect of PDT, the conventional strategy is introducing excess ROS in various ways, such as applying high light doses, high photosensitizer concentrations, and exogenous oxygen. In this study, we report a metallacage-based PDT strategy that minimizes the use of ROS by jointly using gallium-metal organic framework rods to inhibit the production of bacterial endogenous NO, amplify ROS stress, and enhance the killing effect. The augmented bactericidal effect was demonstrated both in vitro and in vivo. This proposed enhanced PDT strategy will provide a new option for bacterial ablation. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus persistently colonizes the nasopharynx in humans, which increases the risk for invasive diseases, such as skin infection and bacteremia. Nasal colonization triggers IgG responses against staphylococcal surface antigens; however, these antibodies cannot prevent subsequent colonization or disease. Here, we describe S. aureus WU1, a multilocus sequence type 88 (ST88) isolate that persistently colonizes the nasopharynx in mice. We report that staphylococcal protein A (SpA) is required for persistence of S. aureus WU1 in the nasopharynx. Compared to animals colonized by wild-type S. aureus, mice colonized with the Δspa variant mount increased IgG responses against staphylococcal colonization determinants. Immunization of mice with a nontoxigenic SpA variant, which cannot cross-link B cell receptors and divert antibody responses, elicits protein A-neutralizing antibodies that promote IgG responses against colonizing S. aureus and diminish pathogen persistence. [ABSTRACT FROM AUTHOR]

Lymph node metastasis is the most common form of metastasis in breast cancer and a crucial indicator influencing breast cancer treatment results. The biological process of lymph node metastasis involves deficiency and mutation of tumor suppressor genes. PTEN and SHIP are critical indicators used to detect occurrence, development, invasion, and metastasis of breast cancer. Loss of expressions of PTEN and SHIP may contribute to lymphatic metastasis of breast cancer, so they can be used as objective indicators for judging the biological behavior of breast cancer. In this study, we perform a comprehensive analysis to investigate the effect of PTEN and SHIP gene expression on regulating lymph node metastasis in breast cancer. [ABSTRACT FROM AUTHOR]

Recent experiments revealed that Mn3Sn and Mn3Ge exhibit a strong anomalous Hall effect at room temperature, provoking us to explore their electronic structures for topological properties. By abinitio band structure calculations, we have observed the existence of multiple Weyl points in the bulk and corresponding Fermi arcs on the surface, predicting antiferromagnetic Weyl semimetals in Mn3Ge and Mn3Sn. Here the chiral antiferromagnetism in the Kagome-type lattice structure is essential to determine the positions and numbers of Weyl points. Our work further reveals a new guiding principle to search for magnetic Weyl semimetals among materials that exhibit a strong anomalous Hall effect. [ABSTRACT FROM AUTHOR]