强直性脊柱炎新骨形成机制研究进展

强直性脊柱炎（Ankylosing spondylitis, AS）是以骶髂关节和脊柱病变为主的炎性疾病。其特征性病理表现为炎症和新骨形 成。近年来使用肿瘤坏死因子（Tumor necrosis factor,TNF）抑制剂控制AS 炎症已卓有成效,却无法阻止影像学进程,其病理性新 骨形成可致残,严重影响患者健康生活,但其机制尚不完全清楚。目前研究认为复杂的新骨形成机制与Wnt/beta-catenin信号通路及 其调控因子、炎症介质密切相关。本文结合当前国内外的研究就AS 新骨形成机制进展展开综述,为深入研究新骨形成机制提供 新思想。     

Acoustic activity across a seabird colony reflects patterns of within-colony flight rather than nest density

Passive acoustic monitoring is increasingly being used as a cost-effective way to study wildlife populations, especially those that are difficult to census using conventional methods. Burrow-nesting seabirds are among the most threatened birds globally, but they are also one of the most challenging taxa to census, making them prime candidates for research into such automated monitoring platforms. Passive acoustic monitoring has the potential to determine presence/absence or quantify burrow-nesting populations, but its effectiveness remains unclear. We compared passive acoustic monitoring, tape-playbacks and GPS tracking data to investigate the ability of passive acoustic monitoring to capture unbiased estimates of within-colony variation in nest density for the Manx Shearwater Puffinus puffinus. Variation in acoustic activity across 12 study plots on an island colony was examined in relation to burrow density and environmental factors across 2 years. As predicted fewer calls were recorded when wind speed was high, and on moon-lit nights, but there was no correlation between acoustic activity and the density of breeding birds within the plots as determined by tape-playback surveys. Instead, acoustic indices correlated positively with spatial variation in the in-colony flight activity of breeding individuals detected by GPS. Although passive acoustic monitoring has enormous potential in avian conservation, our results highlight the importance of understanding behaviour when using passive acoustic monitoring to estimate density and distribution.     

Hippocampal replay reflects specific past experiences rather than a plan for subsequent choice

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Evidence that accumulation of mutants in a biofilm reflects natural selection rather than stress-induced adaptive mutation

The accumulation of mutant genotypes within a biofilm evokes the controversy over whether the biofilm environment induces adaptive mutation or whether the accumulation can be explained by natural selection. A comparison of the virulence of two strains of the dental pathogen Streptococcus mutans showed that rats infected with one of the strains accumulated a high proportion (average, 22%) of organisms that had undergone a deletion between two contiguous and highly homologous genes. To determine if the accumulation of deletion mutants was due to selection or to an increased mutation rate, accumulations of deletion mutants within in vitro planktonic and biofilm cultures and within rats inoculated with various proportions of deletion organisms were quantified. We report here that natural selection was the primary force behind the accumulation of the deletion mutants.     

Neural oscillations are a start toward understanding brain activity rather than the end

Does rhythmic neural activity merely echo the rhythmic features of the environment, or does it reflect a fundamental computational mechanism of the brain? This debate has generated a series of clever experimental studies attempting to find an answer. Here, we argue that the field has been obstructed by predictions of oscillators that are based more on intuition rather than biophysical models compatible with the observed phenomena. What follows is a series of cautionary examples that serve as reminders to ground our hypotheses in well-developed theories of oscillatory behavior put forth by theoretical study of dynamical systems. Ultimately, our hope is that this exercise will push the field to concern itself less with the vague question of “oscillation or not” and more with specific biophysical models that can be readily tested.     

Differential resistance to growth of a tumor expressing incompatible minor alloantigens reflects regulatory influences rather than differences in anti-minor-CTL-P frequencies

In previous studies it was found that BALB/c (H-2d) was more susceptible than (BALB/c X A)F1 (H-2d X H-2a) to a tumor bearing multiple mismatched minor histocompatibility antigens, the DBA/2 (H-2d) mastocytoma P815, and that this resistance was H-2 linked. In the present studies the immunologic basis of this effect was examined by comparing the cytotoxic-T-lymphocyte (CTL) responses of BALB/c with those of (BALB/c X A)F1. Despite the BALB/c X A)F1's 34-fold greater resistance to P815 in vivo, the numbers of effector cell precursors were found to be similar in the two hosts as shown by (a) similar anti-P815 CTL responses in vitro with T-cell growth factor, (b) similar secondary anti-DBA/2 MiHA responses after in vivo priming with irradiated P815, and (c) similar frequencies of anti-DBA/2 CTL precursors by limiting-dilution analysis. However, priming with proliferating P815 in vivo revealed a defect in the BALB/c animals: Spleen cells from such animals were unable to control the growth of contaminating P815 cells in vitro or to mount strong secondary CTL responses to DBA/2 antigens. The defective priming of BALB/c could be corrected when DBA/2 spleen cells were added to the P815 inoculum. This impaired priming by living tumor cells was not seen in (BALB/c X A)F1. It is concluded that the use of living P815 tumor cells revealed a defect in immunoregulation in BALB/c mice, which rendered them susceptible to tumor growth in spite of apparently adequate numbers of anti-minor-CTL precursors. How the additional H-2 products expressed in the (BALB/c X A)F1 might correct this defect is discussed.     

Markers of intestinal inflammation in patients with ankylosing spondylitis: a pilot study

Introduction

Inflammatory bowel disease (IBD) and ankylosing spondylitis (AS) are similar chronic inflammatory diseases whose definitive etiology is unknown. Following recent clinical and genetic evidence supporting an intertwined pathogenic relationship, we conducted a pilot study to measure fecal calprotectin (fCAL) and IBD-related serologies in AS patients.

Methods

Consecutive AS patients were recruited from a long-term prospectively collected longitudinal AS cohort at Cedars-Sinai Medical Center. Controls were recruited from Cedars-Sinai Medical Center employees or spouses of patients with AS. Sera were tested by ELISA for IBD-associated serologies (antineutrophil cytoplasmic antibodies (ANCA), anti-Saccharomyces cerevisiae antibody IgG and IgA, anti-I2, anti-OmpC, and anti-CBir1). The Bath Ankylosing Spondylitis Disease Activity Index, the Bath Ankylosing Spondylitis Functional Index, and the Bath Ankylosing Spondylitis Radiology Index were completed for AS patients.

Results

A total of 81 subjects (39 AS patients and 42 controls) were included for analysis. The average age of AS patients was 47 years and the average disease duration was 22 years. AS patients were predominantly male; 76% were HLA-B27-positive. Median fCAL levels were 42 μg/g and 17 μg/g in the AS group and controls, respectively (P < 0.001). When using the manufacturer''s recommended cutoff value for positivity of 50 μg/g, stool samples of 41% of AS patients and 10% of controls were positive for fCAL (P = 0.0016). With the exception of ANCA, there were no significant differences in antibody levels between patients and controls. Median ANCA was 6.9 ELISA units in AS patients and 4.3 ELISA units in the controls. Among AS patients stratified by fCAL level, there were statistically significant differences between patients and controls for multiple IBD-associated antibodies.

Conclusion

Calprotectin levels were elevated in 41% of patients with AS with a cutoff value for positivity of 50 μg/g. fCAL-positive AS patients displayed higher medians of most IBD-specific antibodies when compared with healthy controls or fCAL-negative AS patients. Further studies are needed to determine whether fCAL can be used to identify and characterize a subgroup of AS patients whose disease might be driven by subclinical bowel inflammation.     

Antithromboxane activity of dietary alpha-linolenic acid: a pilot study

Two decades of research conclusively demonstrated the antithrombotic properties of the long-chain n-3 polyunsaturated fatty acids (PUFA) present in lipids from marine fishes. Most American consumers, however, given their preference for meat, will not realize the benefits of a fish-rich diet. Could α-linolenic acid (18:3, n-3) be similarly effective via modulation of the synthesis of vasoactive eicosanoids, i.e., thromboxane and prostacyclin? The present pilot study is a contribution toward answering this question. We determined that the urinary excretion of 11-dehydrothromboxane B₂ declined by 34% from baseline level 7 weeks after the ratio of dietary PUFA was reduced from 28:1 to 1:1. The excretion of 2,3-dinor-6-oxo-prostaglandin F_1α was similarly affected. The dietary adjustment was brought about by substituting measured amounts of canola and flaxseed oils (3:1) for measured amounts of olive and corn oils (3:1) in an otherwise fat-free basal diet. This study demonstrates that dietary α-linolenic acid is an effective modulator of thromboxane and prostacyclin biosynthesis. Therefore, we can expect that the eicosanoid-mediated effects of α-linolenic acid are similar to those elicited by marine lipids.     

Modularity in attachment organs of African Cichlidogyrus (Platyhelminthes: Monogenea: Ancyrocephalidae) reflects phylogeny rather than host specificity or geographic distribution

Cichlidogyrus spp. (Monogenea, Ancyrocephalidae) are common parasites of cichlid fishes from Africa and the Levant. They display important morphological variation in their attachment apparatus and infect a broad host spectrum throughout a wide geographic range. Thus, they offer an interesting model to investigate to what extent the phenotypic variability of the attachment organ among congeners is related to host specificity, geographic/environmental components, or phylogeny. A geometric morphometric approach was carried out to analyse the shape variation of sclerotized structures of the attachment organ within 66 African species of the genus Cichlidogyrus. The interspecific shape comparison supports the presence of three main morphological configurations, each consisting of a given combination of particular sclerite shapes. Moreover, data emphasize strong coordination and integration (shape co‐variation) among the different sclerites jointly forming the attachment organ. Although attachment apparatuses are usually considered to be the result of adaptive processes and must be adapted to the hosts and local environmental conditions, we found no relationship between these clusters and host specificity or geographical distribution. Nevertheless, groups are partially congruent with those obtained with the molecular phylogeny of a subset of species, suggesting a phylogenetic constraint rather than an adaptation to either hosts or environment. Because of the necessity to form a functional entity, modularity within attachment organ imposes important evolutionary constraint. This provides new insights into the evolvability of attachment organs, as well as into the morphological basis of host specificity and host–parasite co‐evolutionary interaction in helminth parasites. © 2011 The Linnean Society of London, Biological Journal of the Linnean Society, 2011, 102 , 694–706.     

Possible activity of acidic fibroblast growth factor as a progression factor rather than a transforming factor.

Acidic and basic fibroblast growth factors (aFGF and bFGF) are mitogens for mesoderm- and neuroectoderm-derived cells. The facts that FGF-related proteins are oncogenic and that FGFs are expressed in a variety of tumor cell lines or tumor tissues suggest the transforming activities of FGFs. To examine such an activity of aFGF, we introduced a human aFGF expression vector into two populations of Rat-1 cells; one was non-transformed (nRat-1), the other was partially-transformed (tRat-1). tRat-1 cells transfected with aFGF cDNA formed larger colonies in soft agar and produced larger and more malignant tumors in nude mice than those of parental cells. In contrast, nRat-1 cells transfected with aFGF cDNA neither formed colonies in soft agar nor produced tumors in nude mice. Our results suggest that high expression of aFGF may enhance a tumorigenic potential of Rat-1 cells rather than confer such a potential de novo.     

N-acyl-homoserine lactone-mediated quorum-sensing in Azospirillum: an exception rather than a rule

Forty Azospirillum strains were tested for their ability to synthesize N-acyl-homoserine lactones (AHLs). AHL production was detected for four strains belonging to the lipoferum species and isolated from a rice rhizosphere. AHL molecules were structurally identified for two strains: Azospirillum lipoferum TVV3 produces 3O,C(8)-HSL (N-3-oxo-octanoyl-homoserine-lactone), C(8)-HSL (N-3-octanoyl-homoserine-lactone), 3O,C(10)-HSL (N-3-oxo-decanoyl-homoserine-lactone), 3OH,C(10)-HSL (N-3-hydroxy-decanoyl-homoserine-lactone) and C(10)-HSL (N-3-decanoyl-homoserine-lactone), whereas A. lipoferum B518 produced 3O,C(6)-HSL (N-3-oxo-hexanoyl-homoserine-lactone), C(6)-HSL (N-3-hexanoyl-homoserine-lactone), 3O,C(8)-HSL, 3OH,C(8)-HSL and C(8)-HSL. Genes involved in AHL production were characterized for A. lipoferum TVV3 by generating a genomic library and complementing an AHL-deficient strain with sensor capabilities. Those genes, designated alpI and alpR, were found to belong to the luxI and luxR families, respectively. When cloned in a suitable heterologous host, alpI and alpR could direct the synthesis of the five cognate AHLs present in A. lipoferum TVV3. These two adjacent genes were found to be located on a 85 kb plasmid. Southern hybridization experiments with probes alpI/R indicated that genes involved in AHL production in the three other AHL-producing strains were not closely related to alpI and alpR. This study demonstrates that AHL-based quorum-sensing is not widespread among the genus Azospirillum and could be found only in some A. lipoferum strains.     

Gulping rather than sipping: macropinocytosis as a way of virus entry

Macropinocytosis has emerged as a major endocytic mechanism in the cell entry of animal viruses. The process differs fundamentally from other endocytic mechanisms involved in virus internalization. By activating growth factor receptors or other signaling molecules, plasma membrane-bound viruses trigger the activation of a signaling pathway. When amplified, this causes a transient, global change in cell behavior. The consequences of this change include the actin-dependent formation of membrane protrusions, the elevation of non-specific uptake of fluid, and the internalization of membrane together with surface-bound ligands and particles including viruses. Recent studies show that this strategy is used by a variety of enveloped and non-enveloped viruses.     

Up-regulation of gamma-glutamyl transpeptidase activity following glutathione depletion has a compensatory rather than an inhibitory effect on mitochondrial complex I activity: implications for Parkinson's disease

Up-regulation of activity of gamma-glutamyl transpeptidase (GGT) has been reported to occur in the Parkinsonian substantia nigra, the area of the brain affected by the disease. Increased GGT activity has been hypothesized to play a role in subsequent mitochondrial complex I (CI) inhibition by increasing cysteine as substrate for cellular uptake. Intracellular cysteine has been proposed to form toxic adducts with dopamine which can be metabolized to compounds which inhibit CI activity. We have demonstrated that in addition to CI inhibition, GGT activity is up-regulated in dopaminergic cells as a consequence of glutathione depletion. Inhibition of GGT rather than resulting in increased CI inhibition results in exacerbation of this inhibitory effect. This suggests that increased GGT activity is likely an adaptive response to the loss of glutathione to conserve intracellular glutathione content and results in a compensatory effect on CI activity rather than in its inhibition as has been previously widely hypothesized.     

Renaming restoration: conceptualizing and justifying the activity as a restoration of lost moral value rather than a return to a previous state

A significant percentage of contemporary restoration work, while informed by history, aims for a novel state rather than an exact simulacrum of any particular historical state. However, the lay definition of “restoration” is to return something to its original state, and this influences public perceptions—and perhaps perceptions inside the field—about what the goals of restoration are. Relying on history to justify the proposed end state of a restoration project is problematic because of climate change, knowledge gaps, and the fact that ecosystems are dynamic and have no single historical state. Restorationists should be open to discussing whether the name of their field is inaccurate and considering alternatives. The process productively forces them to think about, articulate, and justify their values. One possible outcome of this process is a redefinition of “restoration” to mean a restoration of moral value rather than a restoration of a historical state. Restorationists will need to be comfortable talking about choices, intentions, values, and justifications in a world where historical fidelity no longer reigns supreme.     

Ants have a negative rather than a positive effect on extrafloral nectaried Crotalaria pallida performance

Crotalaria pallida (Fabaceae) is a pantropical plant with extrafloral nectaries (EFNs) near the reproductive structures. EFN-visiting ants attack and remove arctiid moth Utetheisa ornatrix larvae, the main pre-dispersal seed predator, but the impact of ants on C. pallida fitness is unknown. To assess this impact, we controlled ant presence on plants and evaluated the reproductive output of C. pallida with and without ants. Predatory wasps also visit EFNs, prey upon U. ornatrix larvae, and may be driven out by ants during EFN feeding. Does this agonistic interaction affect the multitrophic interaction outcome? We found it difficult to evaluate the effect of both visitors because cages excluding wasps affect plant growth and do not allow U. ornatrix oviposition. Therefore, we verified whether ant presence inhibited wasp EFN visitation and predicted that (1) if ants confer a benefit for C. pallida, any negative effect of ants on wasps would be negligible for the plant because ants would be the best guardians, and (2) if ants are poor guardians, they would negatively affect wasps and negatively impact the fitness of C. pallida. Surprisingly, we found that the number of seeds/pods significantly increased, ca. 4.7 times, after ant removal. Additionally, we unexpectedly verified that controls showed a higher percentage of herbivore bored pods than ant-excluded plants. We found that wasps spent less time visiting EFNs patrolled by ants (ca. 299 s less). These results support our second prediction and suggest that the outcome of multitrophic interactions may vary with natural enemy actors.     

Central rather than overall obesity is related to diabetes in the Chinese population: the InterASIA study

Objective: The objective was to compare central and overall obesity measurements for identifying diabetes mellitus (DM) and impaired fasting glucose (IFG) level in the Chinese population. Research Methods and Procedures: Data for 15,236 Chinese adults between the ages of 35 and 74 years, obtained by the InterASIA Study in 2000–2001, were used for the current analyses. We analyzed the areas under the receiver operating characteristic (ROC) curves (AUCs) for waist circumference (WC), waist‐to‐hip ratio (WHR), and BMI to determine the ability of these indices to identify DM and IFG in the study sample and bootstrapped samples. WC was used as a measure of central obesity and BMI as a measure of overall obesity. Results: The prevalence rates of central and overall obesity in the study population were 33.97% and 9.78%, respectively. The prevalence rates of IFG and DM were 7.34% and 5.51%, respectively. ROC analysis revealed significant differences between AUCs for WHR (0.666, 95% confidence interval, 0.647 to 0.685) and BMI (0.622, 95% confidence interval, 0.601 to 0.642) and for WC (0.661, 95% confidence interval, 0.643 to 0.682) and BMI for identifying DM (all p < 0.0001). The analysis also revealed significant differences between AUCs for WHR (0.638, 95% confidence interval, 0.619 to 0.655) and BMI (0.607, 95% confidence interval, 0.589 to 0.627) and for WC (0.637, 95% confidence interval, 0.615 to 0.654) and BMI for identifying IFG (all p < 0.001). Discussion: Central obesity is more related to DM and IFG than is overall obesity in the Chinese population, and both WC and WHR are equally able to identify DM.