Numerosity perception is a process involving several stages of visual processing. This study investigated whether distinct mechanisms exist in numerosity adaptation under different awareness conditions to characterize how numerosity perception occurs at each stage. The status of awareness was controlled by masking conditions, in which monoptic and dichoptic masking were proposed to influence different levels of processing. Numerosity adaptation showed significant aftereffects when the participants were aware (monoptic masking) and unaware (dichoptic masking) of adaptors. The interocular transfer for numerosity adaptation was distinct under the different awareness conditions. Adaptation was primarily binocular when participants were aware of stimuli and was purely monocular when participants were unaware of adaptors. Moreover, numerosity adaptation was significantly reduced when the adaptor dots were clustered into chunks with awareness, whereas clustering had no effect on unaware adaptation. These results show that distinct mechanisms exist in numerosity processing under different awareness conditions. It is suggested that awareness is crucial to numerosity cognition. With awareness, grouping (by clustering) influences numerosity coding through altered object representations, which involves higher-level cognitive processing.
Multiple co-occurring environmental changes are affecting soil nitrogen cycling processes, which are mainly mediated by microbes. While it is likely that various nitrogen-cycling functional groups will respond differently to such environmental changes, very little is known about their relative responsiveness. Here we conducted four long-term experiments in a steppe ecosystem by removing plant functional groups, mowing, adding nitrogen, adding phosphorus, watering, warming, and manipulating some of their combinations. We quantified the abundance of seven nitrogen-cycling genes, including those for fixation (nifH), mineralization (chiA), nitrification (amoA of ammonia-oxidizing bacteria (AOB) or archaea (AOA)), and denitrification (nirS, nirK and nosZ). First, for each gene, we compared its sensitivities to different environmental changes and found that the abundances of various genes were sensitive to distinct and different factors. Overall, the abundances of nearly all genes were sensitive to nitrogen enrichment. In addition, the abundances of the chiA and nosZ genes were sensitive to plant functional group removal, the AOB-amoA gene abundance to phosphorus enrichment when nitrogen was added simultaneously, and the nirS and nirK gene abundances responded to watering. Second, for each single- or multi-factorial environmental change, we compared the sensitivities of the abundances of different genes and found that different environmental changes primarily affected different gene abundances. Overall, AOB-amoA gene abundance was most responsive, followed by the two denitrifying genes nosZ and nirS, while the other genes were less sensitive. These results provide, for the first time, systematic insights into how the abundance of each type of nitrogen-cycling gene and the equilibrium state of all these nitrogen-cycling gene abundances would shift under each single- or multi-factorial global change.
Yoga is thought to be effective for health conditions. The article aims to assess the current clinical evidence of yoga for Essential hypertension (EH).
MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library were searched until June, 2013. We included randomized clinical trials testing yoga against conventional therapy, yoga versus no treatment, yoga combined with conventional therapy versus conventional therapy or conventional therapy combined with breath awareness. Study selection, data extraction, quality assessment, and data analyses were conducted according to the Cochrane standards.
A total of 6 studies (involving 386 patients) were included. The methodological quality of the included trials was evaluated as generally low. A total of 6 RCTs met all the inclusion criteria. 4 of them compared yoga plus conventional therapy with conventional therapy. 1 RCT described yoga combined with conventional therapy versus conventional therapy combined with breath awareness. 2 RCT tested the effect of yoga versus conventional therapy alone. 1 RCT described yoga compared to no treatment. Only one trial reported adverse events without details, the safety of yoga is still uncertain.
There is some encouraging evidence of yoga for lowering SBP and DBP. However, due to low methodological quality of these identified trials, a definite conclusion about the efficacy and safety of yoga on EH cannot be drawn from this review. Therefore, further thorough investigation, large-scale, proper study designed, randomized trials of yoga for hypertension will be required to justify the effects reported here.
Yunnan, Guangxi and Henan are the provinces with the most severe HIV epidemic in China, which were also among the first group of areas providing free ART in 2004. However, little comprehensive data are available on prevalence of HIV subtype and baseline drug resistance in drug-naïve populations. In this study, 1746 treatment-naïve HIV-positive individuals were randomly selected from new-reported cases in Henan, Guangxi and Yunnan. Among of them, subtypes and drug resistance of 1159 strains were determined by amplifying and sequencing full-length pol genes. Significantly different distributions of HIV subtypes prevalent in three provinces were identified (P<0.01). CRF08_BC was found dominant in Yunnan (59.8%), while CRF01_AE was dominant in Guangxi (77.3%) and subtype B was dominant in Henan province (93.9%). The total prevalence of drug resistance was 7.1%. The highest prevalence of HIV drug resistance was found in Henan (12.2%), followed by Yunnan (5.6%) and Guangxi (3.3%). The results of this study suggest that genetic drug-resistance should be tested before initiation of ART in China, especially in Henan province. Furthermore, the prevalence of HIV drug resistant strains should be considered separately in different areas in China before the change of different free ART regimens.
Iterative Cross-Correlation (ICC) is the most popularly used schema for correcting eddy current (EC)-induced distortion in diffusion-weighted imaging data, however, it cannot process data acquired at high b-values. We analyzed the error sources and affecting factors in parameter estimation, and propose an efficient algorithm by expanding the ICC framework with a number of techniques: (1) Pattern recognition for excluding brain ventricles; (2) ICC with the extracted ventricle for parameter initialization; (3) Gradient-based Entropy Correlation Coefficient (GECC) for optimal and finer registration. Experiments demonstrated that our method is robust with high accuracy and error tolerance, and outperforms other ICC-family algorithms and popular approaches currently in use.
diffusion weighted imaging; diffusion tensor imaging; eddy current; distortion correction; iterative cross-correlation; mutual information
Although mammography is the only clinically accepted imaging modality for screening the general population to detect breast cancer, interpreting mammograms is difficult with lower sensitivity and specificity. To provide radiologists “a visual aid” in interpreting mammograms, we developed and tested an interactive system for computer-aided detection and diagnosis (CAD) of mass-like cancers. Using this system, an observer can view CAD-cued mass regions depicted on one image and then query any suspicious regions (either cued or not cued by CAD). CAD scheme automatically segments the suspicious region or accepts manually defined region and computes a set of image features. Using content-based image retrieval (CBIR) algorithm, CAD searches for a set of reference images depicting “abnormalities” similar to the queried region. Based on image retrieval results and a decision algorithm, a classification score is assigned to the queried region. In this study, a reference database with 1,800 malignant mass regions and 1,800 benign and CAD-generated false-positive regions was used. A modified CBIR algorithm with a new function of stretching the attributes in the multi-dimensional space and decision scheme was optimized using a genetic algorithm. Using a leave-one-out testing method to classify suspicious mass regions, we compared the classification performance using two CBIR algorithms with either equally weighted or optimally stretched attributes. Using the modified CBIR algorithm, the area under receiver operating characteristic curve was significantly increased from 0.865 ± 0.006 to 0.897 ± 0.005 (p < 0.001). This study demonstrated the feasibility of developing an interactive CAD system with a large reference database and achieving improved performance.
Computer-aided detection and diagnosis (CAD); Content-based image retrieval (CBIR); Breast cancer; Mammograms
The distribution of HIV-1 subtypes and genetic characterization of CRF01_AE in Guangxi, southern China were identified. The distribution of HIV-1 genotypes based on gag, pol, and partial env sequences (n=349) was as follows: CRF01_AE (66.5%), CRF08_BC (19.2%), CRF07_BC (7.2%), URF (4.6%), subtype B (1.7%), and subtype B′ (0.9%). CRF01_AE predominated in all geographic regions and risk populations and there were multiple introductions of CRF01_AE strains in Guangxi. We found a peculiar CRF01_AE monophyletic lineage distinct from other CRF01_AE viruses, and we designated it “CRF01_AE-v” for convenience. CRF01_AE-v circulating in both heterosexuals and injecting drug users (IDUs) had accounted for 39.7% of CRF01_AE. It showed a selective advantage in the Guangxi population and formed its own characteristic compared with all the CRF01_AE references. Our results suggested that CRF01_AE-v was a new variant of CRF01_AE and it might lead to a new epidemic in Guangxi.
Mesenchymal stem cell (MSC) transplantation has been proposed as a potential therapeutic approach for ischemic heart disease, but the regenerative capacity of these cells decreases with age. In this study, we genetically engineered old human MSCs (O-hMSCs) with tissue inhibitor of matrix metalloproteinase-3 (TIMP3) and vascular endothelial growth factor (VEGF) and evaluated the effects on the efficacy of cell-based gene therapy in a rat myocardial infarction (MI) model. Cultured O-hMSCs were transfected with TIMP3 (O-TIMP3) or VEGF (O-VEGF) and compared with young hMSCs (Y-hMSCs) and non-transfected O-hMSCs for growth, clonogenic capacity, and differentiation potential. In vivo, rats were subjected to left coronary artery ligation with subsequent injection of Y-hMSCs, O-hMSCs, O-TIMP3, O-VEGF, or medium. Echocardiography was performed prior to and at 1, 2, and 4 weeks after MI. Myocardial levels of matrix metalloproteinase-2 (MMP2), MMP9, TIMP3, and VEGF were assessed at 1 week. Hemodynamics, morphology, and histology were measured at 4 weeks. In vitro, genetically modified O-hMSCs showed no changes in growth, colony formation, or multi-differentiation capacity. In vivo, transplantation with O-TIMP3, O-VEGF, or Y-hMSCs increased capillary density, preserved cardiac function, and reduced infarct size compared to O-hMSCs and medium control. O-TIMP3 and O-VEGF transplantation enhanced TIMP3 and VEGF expression, respectively, in the treated animals. O-hMSCs genetically modified with TIMP3 or VEGF can increase angiogenesis, prevent adverse matrix remodeling, and restore cardiac function to a degree similar to Y-hMSCs. This gene-modified cell therapy strategy may be a promising clinical treatment to rejuvenate stem cells in elderly patients.
Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel bunyavirus that recently emerged in China. Infection with SFTSV is associated with case-fatality rates of up to 30%, and neither antivirals nor vaccines are available at present. Development of antiviral strategies requires the elucidation of virus-host cell interactions. Here, we analyzed host cell entry of SFTSV. Employing lentiviral and rhabdoviral vectors, we found that the Gn/Gc glycoproteins (Gn/Gc) of SFTSV mediate entry into a broad range of human and animal cell lines, as well as human macrophages and dendritic cells. The Gn/Gc proteins of La Crosse virus (LACV) and Rift Valley Fever Virus (RVFV), other members of the bunyavirus family, facilitated entry into an overlapping but not identical range of cell lines, suggesting that SFTSV, LACV, and RVFV might differ in their receptor requirements. Entry driven by SFTSV Gn/Gc was dependent on low pH but did not require the activity of the pH-dependent endosomal/lysosomal cysteine proteases cathepsins B and L. Instead, the activity of a cellular serine protease was required for infection driven by SFTSV and LACV Gn/Gc. Sera from convalescent SFTS patients inhibited SFTSV Gn/Gc-driven host cell entry in a dose-dependent fashion, demonstrating that the vector system employed is suitable to detect neutralizing antibodies. Finally, the C-type lectin DC-SIGN was found to serve as a receptor for SFTSV Gn/Gc-driven entry into cell lines and dendritic cells. Our results provide initial insights into cell tropism, receptor usage, and proteolytic activation of SFTSV and will aid in the understanding of viral spread and pathogenesis.
The viequeamides, a family of 2,2-dimethyl-3-hydroxy-7-octynoic acid (Dhoya) containing cyclic depsipeptides, were isolated from a shallow subtidal collection of a ‘button’ cyanobacterium (Rivularia sp.) from near the island of Vieques, Puerto Rico. Planar structures of the two major compounds, viequeamide A (1) and viequeamide B (2), were elucidated by 2D-NMR spectroscopy and mass spectrometry, whereas absolute configurations were determined by traditional hydrolysis, derivative formation, and chromatography in comparison with standards. In addition, a series of related minor metabolites, viequeamide C–F (3–6), were characterized by high resolution mass spectroscopic (HRMS) fragmentation methods. Viequeamide A was found to be highly toxic to H460 human lung cancer cells (IC50 = 60 ± 10 nM), whereas the mixture of B–F was inactive. From a broader perspective, the viequeamides help to define a “superfamily” of related cyanobacterial natural products, the first of which to be discovered was ‘kulolide’. Within the kulolide superfamily, a wide variation in biological properties is observed, and the reported producing strains are also highly divergent, giving rise to several intriguing questions about structure-activity relationships and the evolutionary origins of this metabolite class.
While the experimental Alzheimer's drugs recently developed by pharmaceutical companies failed to stop the progression of Alzheimer's disease, clinicians strive to seek clues on how the patients would be when they visit back next year, based upon the patients' current clinical and neuropathologic diagnosis results. This is related to how to precisely identify the transitional patterns of Alzheimer's disease. Due to the complexities of the diagnosis of Alzheimer's disease, the condition of the disease is usually characterized by multiple clinical and neuropathologic measurements, including Clinical Dementia Rating (CDRGLOB), Mini-Mental State Examination (MMSE), a score derived from the clinician judgement on neuropsychological tests (COGSTAT), and Functional Activities Questionnaire (FAQ). In this research article, we investigate a class of novel joint random-effects transition models that are used to simultaneously analyze the transitional patterns of multiple primary measurements of Alzheimer's disease and, at the same time, account for the association between the measurements. The proposed methodology can avoid the bias introduced by ignoring the correlation between primary measurements and can predict subject-specific transitional patterns.
China experienced several large measles outbreaks in the past two decades, and a series of enhanced control measures were implemented to achieve the goal of measles elimination. Molecular epidemiologic surveillance of wild-type measles viruses (MeV) provides valuable information about the viral transmission patterns. Since 1993, virologic surveillnace has confirmed that a single endemic genotype H1 viruses have been predominantly circulating in China. A component of molecular surveillance is to monitor the genetic characteristics of the hemagglutinin (H) gene of MeV, the major target for virus neutralizing antibodies.
Analysis of the sequences of the complete H gene from 56 representative wild-type MeV strains circulating in China during 1993–2009 showed that the H gene sequences were clustered into 2 groups, cluster 1 and cluster 2. Cluster1 strains were the most frequently detected cluster and had a widespread distribution in China after 2000. The predicted amino acid sequences of the H protein were relatively conserved at most of the functionally significant amino acid positions. However, most of the genotype H1 cluster1 viruses had an amino acid substitution (Ser240Asn), which removed a predicted N-linked glycosylation site. In addition, the substitution of Pro397Leu in the hemagglutinin noose epitope (HNE) was identified in 23 of 56 strains. The evolutionary rate of the H gene of the genotype H1 viruses was estimated to be approximately 0.76×10−3 substitutions per site per year, and the ratio of dN to dS (dN/dS) was <1 indicating the absence of selective pressure.
Although H genes of the genotype H1 strains were conserved and not subjected to selective pressure, several amino acid substitutions were observed in functionally important positions. Therefore the antigenic and genetic properties of H genes of wild-type MeVs should be monitored as part of routine molecular surveillance for measles in China.
The structure of the Tse3–Tsi3 complex associated with the bacterial type VI secretion system of P. aeruginosa has been solved and refined at 1.9 Å resolution. The structural basis of the recognition of the muramidase effector and its inactivation by its cognate immunity protein is revealed.
The type VI secretion system (T6SS) is a bacterial protein-export machine that is capable of delivering virulence effectors between Gram-negative bacteria. The T6SS of Pseudomonas aeruginosa transports two lytic enzymes, Tse1 and Tse3, to degrade cell-wall peptidoglycan in the periplasm of rival bacteria that are competing for niches via amidase and muramidase activities, respectively. Two cognate immunity proteins, Tsi1 and Tsi3, are produced by the bacterium to inactivate the two antibacterial effectors, thereby protecting its siblings from self-intoxication. Recently, Tse1–Tsi1 has been structurally characterized. Here, the structure of the Tse3–Tsi3 complex is reported at 1.9 Å resolution. The results reveal that Tse3 contains a C-terminal catalytic domain that adopts a soluble lytic transglycosylase (SLT) fold in which three calcium-binding sites were surprisingly observed close to the catalytic Glu residue. The electrostatic properties of the substrate-binding groove are also distinctive from those of known structures with a similar fold. All of these features imply that a unique catalytic mechanism is utilized by Tse3 in cleaving glycosidic bonds. Tsi3 comprises a single domain showing a β-sandwich architecture that is reminiscent of the immunoglobulin fold. Three loops of Tsi3 insert deeply into the groove of Tse3 and completely occlude its active site, which forms the structural basis of Tse3 inactivation. This work is the first crystallographic report describing the three-dimensional structure of the Tse3–Tsi3 effector–immunity pair.
muramidases; peptidoglycan; effectors; immunity; calcium binding; interaction
Saccharopolyspora erythraea is a Gram-positive bacterium that can produce antibiotics. However, this microorganism must often be genetically improved for higher production before it can be used in an industrial setting. Here, we report the whole-genome sequence of the industrial hyperproducer strong mutator Saccharopolyspora erythraea strain D.
Proliferating tumor cells use aerobic glycolysis to support their high metabolic demands. Paradoxically, increased glycolysis is often accompanied by expression of the lower activity PKM2 isoform, effectively constraining lower glycolysis. Here, we report the discovery of PKM2 activators with a unique allosteric binding mode. Characterization of how these compounds impact cancer cells revealed an unanticipated link between glucose and amino acid metabolism. PKM2 activation resulted in a metabolic rewiring of cancer cells manifested by a profound dependency on the nonessential amino acid serine for continued cell proliferation. Induction of serine auxotrophy by PKM2 activation was accompanied by reduced carbon flow into the serine biosynthetic pathway and increased expression of high affinity serine transporters. These data support the hypothesis that PKM2 expression confers metabolic flexibility to cancer cells that allows adaptation to nutrient stress.
In the title compound, C19H15N3O2·H2O, the oxadiazole ring and the quinoline unit are almost coplanar, making a dihedral angle of 7.66 (8)°. The dihedral angle between the benzene ring and the quinoline system is 25.95 (8)° while that between the benzene and the oxadiazole rings is 18.88 (9)°. The water molecule is hydrogen bonded to an oxadiazole N atom and to the quinoline N atom. In the crystal, these units are linked via C—H⋯O hydrogen bonds, forming two-dimensional networks lying parallel to the ab plane.
The title compound, C20H20Br4N2, is a product of the condensation reaction of 4,6-dibromo-2,3-dimethylaniline and butane-2,3-dione. The molecule has a center of symmetry at the mid-point of the central C—C bond. The dihedral angle between the benzene ring and the 1,4-diazabutadiene plane is 78.3 (2)°. Niether hydrogen bonding nor aromatic stacking is observed in the crystal structure.
Proline dehydrogenase (oxidase, PRODH/POX), the first enzyme in the pathway of proline catabolism, has been identified as a mitochondrial, metabolic tumor suppressor, which is downregulated in a variety of human tumors. However, our recent findings show that PRODH/POX is upregulated by hypoxia in vitro and in vivo. The combination of low glucose and hypoxia produces additive effects on PRODH/POX expression. Both hypoxia and glucose depletion enhance PRODH/POX expression through AMP-activated protein kinase (AMPK) activation to promote tumor cell survival. Nevertheless, the mechanisms underlying PRODH/POX prosurvival functions are different for hypoxia and low-glucose conditions. Glucose depletion with or without hypoxia elevates PRODH/POX and proline utilization to supply ATP for cellular energy needs. Interestingly, under hypoxia PRODH/POX induces protective autophagy by generating reactive oxygen species (ROS). AMPK is the main initiator of stress-triggered autophagy. Thus, PRODH/POX acts as a downstream effector of AMPK in the activation of autophagy under hypoxia. This regulation was confirmed to be independent of the mechanistic target of rapamycin (MTOR) pathway, a major downstream target of AMPK signaling.
apoptosis; autophagy; hypoxia; metabolic stress; proline dehydrogenase/oxidase
Sudden sensorineural hearing loss (SSNHL) is usually unilateral and can be associated with tinnitus and vertigo. The most common causes of this disease are known to be the vascular and viral agents, but immune disorders are involved in the development of sudden deafness. The antiphospholipid syndrome (APS) is an acquired autoimmune system disorder, which is defined as the presence of antiphospholipid antibodies (APA) in the patient’s blood, then cause venous and/or arterial thrombosis in various organs of the body, for example, thrombosis can occur in the placenta and/or the inner ear. As a result, it can cause abortion and/or sudden deafness. Bilateral SSNHL following habitual abortion is a rare clinical event. Here, we report a case of 32-year-old woman who presented with bilateral sudden hearing loss following recurrent pregnancy loss (RPL) as the first manifestation of primary antiphospholipid syndrome. Combine the literature, the diagnosis, clinical implication and treatment are discussed.
Sudden sensorineural hearing loss (SSNHL); autoimmune disease; habitual abortion; recurrent pregnancy loss (RPL); antiphospholipid syndrome (APS); antiphospholipid antibody (APA); anticardiolipin antibody (ACA); thrombosis
Many microbes can be cultured as single-species communities. Often, these colonies are controlled and maintained via the secretion of metabolites. Such metabolites have been an invaluable resource for the discovery of therapeutics (e.g. penicillin, taxol, rapamycin, epothilone). In this article, written for a special issue on imaging mass spectrometry, we show that MALDI-imaging mass spectrometry can be adapted to observe, in a spatial manner, the metabolic exchange patterns of a diverse array of microbes, including thermophilic and mesophilic fungi, cyanobacteria, marine and terrestrial actinobacteria, and pathogenic bacteria. Dependent on media conditions, on average and based on manual analysis, we observed 11.3 molecules associated with each microbial IMS experiment, which was split nearly 50:50 between secreted and colony-associated molecules. The spatial distributions of these metabolic exchange factors are related to the biological and ecological functions of the organisms. This work establishes that MALDI-based IMS can be used as a general tool to study a diverse array of microbes. Furthermore the article forwards the notion of the IMS platform as a window to discover previously unreported molecules by monitoring the metabolic exchange patterns of organisms when grown on agar substrates.
Chinese medicine has evolved from thousands of years of empirical applications and experiences of combating diseases. It has become widely recognized that the Chinese medicine acts through complex mechanisms featured as multicompound, multitarget and multipathway. However, there is still a lack of systematic experimental studies to elucidate the mechanisms of Chinese medicine. In this study, the differentially expressed genes (DEGs) were identified from myocardial infarction rat model treated with Xuesaitong Injection (XST), a Chinese medicine consisting of the total saponins from Panax notoginseng (Burk.) F. H. Chen (Chinese Sanqi). A network-based approach was developed to combine DEGs related to cardiovascular diseases (CVD) with lines of evidence from the literature mining to investigate the mechanism of action (MOA) of XST on antimyocardial infarction. A compound-target-pathway network of XST was constructed by connecting compounds to DEGs validated with literature lines of evidence and the pathways that are functionally enriched. Seventy potential targets of XST were identified in this study, of which 32 were experimentally validated either by our in vitro assays or by CVD-related literatures. This study provided for the first time a network view on the complex MOA of antimyocardial infarction through multiple targets and pathways.
Identifying important species for maintaining ecosystem functions is a challenge in ecology. Since species are components of food webs, one way to conceptualize and quantify species importance is from a network perspective. The importance of a species can be quantified by measuring the centrality of its position in a food web, because a central node may have greater influence on others in the network. A species may also be important because it has a unique network position, such that its loss cannot be easily compensated. Therefore, for a food web to be robust, we hypothesize that central species must be functionally redundant in terms of their network position. In this paper, we test our hypothesis by analysing the Prince William Sound ecosystem. We found that species centrality and uniqueness are negatively correlated, and such an observation is also carried over to other food webs.
species importance; centrality; uniqueness; food web
Identifying functional networks from resting-state functional MRI is a challenging task, especially for multiple subjects. Most current studies estimate the networks in a sequential approach, i.e., they identify each individual subject’s network independently to other subjects, and then estimate the group network from the subjects networks. This one-way flow of information prevents one subject’s network estimation benefiting from other subjects. We propose a hierarchical Markov Random Field model, which takes into account both the within-subject spatial coherence and between-subject consistency of the network label map. Both population and subject network maps are estimated simultaneously using a Gibbs sampling approach in a Monte Carlo Expectation Maximization framework. We compare our approach to two alternative groupwise fMRI clustering methods, based on K-means and Normalized Cuts, using both synthetic and real fMRI data. We show that our method is able to estimate more consistent subject label maps, as well as a stable group label map.