Members Of Subgroup Research Articles

Two New SGI1-LK Variants Found in Proteus mirabilis and Evolution of the SGI1-HKL Group of Salmonella Genomic Islands.

Integrative mobilizable elements belonging to the SGI1-H, -K, and -L Salmonella genomic island 1 (SGI1) variant groups are distinguished by the presence of an alteration in the backbone (IS1359 replaces 2.8 kb of the backbone extending from within traN [S005] to within S009). Members of this SGI1-HKL group have been found in Salmonella enterica serovars and in Proteus mirabilis Two novel variants from this group, designated SGI1-LK1 and SGI1-LK2, were found in the draft genomes of antibiotic-resistant P. mirabilis isolates from two French hospitals. Both variants can be derived from SGI1-PmGUE, a configuration found previously in another P. mirabilis isolate from France. SGI1-LK1 could arise via an IS26-mediated inversion in the complex class 1 integron that duplicated the IS26 element and the target site in IS6100 SGI1-LK1 also has a larger 8.59-kb backbone deletion extending from traN to within S013 and removing traG and traH. However, SGI1-LK1 was mobilized by an IncC plasmid. SGI1-LK2 can be derived from a hypothetical progenitor, SGI1-LK0, that is related to SGI1-PmGUE but lacks the aphA1 gene and one copy of IS26. The integron of SGI1-LK2 could arise via deletion of DNA adjacent to an IS26 and a deletion occurring via homologous recombination between duplicated copies of part of the integron 3'-conserved segment. SGI1-K can also be derived from SGI1-LK0. This would involve an IS26-mediated deletion and an inversion via homologous recombination of a segment between inversely oriented IS26s. Similar events can explain the configuration of the integrons in other SGI1-LK variants.IMPORTANCE Members of the SGI1-HKL subgroup of SGI1-type integrative mobilizable elements have a characteristic alteration in their backbone. They are widely distributed among multiply antibiotic-resistant Salmonella enterica serovars and Proteus mirabilis isolates. The SGI1-K type, found in the globally disseminated multiply antibiotic-resistant Salmonella enterica serovar Kentucky clone ST198 (sequence type 198), and various configurations in the original SGI1-LK group, found in other multiresistant S. enterica serovars and Proteus mirabilis isolates, have complex and highly plastic resistance regions due to the presence of IS26 However, how these complex forms arose and the relationships between them had not been analyzed. Here, a hypothetical progenitor, SGI1-LK0, that can be formed from the simpler SGI1-H is proposed, and the pathways to the formation of new variants, SGI1-LK1 and SGI1-LK2, found in P. mirabilis and other reported configurations via homologous recombination and IS26-mediated events are proposed. This led to a better understanding of the evolution of the SGI1-HKL group.

The transcription factor MML4_D12 regulates fiber development through interplay with the WD40-repeat protein WDR in cotton.

In planta, a vital regulatory complex, MYB-basic helix-loop-helix (bHLH)-WD40 (MBW), is involved in trichome development and synthesis of anthocyanin and proanthocyanin in Arabidopsis. Usually, WD40 proteins provide a scaffold for protein-protein interaction between MYB and bHLH proteins. Members of subgroup 9 of the R2R3 MYB transcription factors, which includes MYBMIXTA-Like (MML) genes important for plant cell differentiation, are unable to interact with bHLH. In this study, we report that a cotton (Gossypium hirsutum) seed trichome or lint fiber-related GhMML factor, GhMML4_D12, interacts with a diverged WD40 protein (GhWDR) in a process similar to but different from that of the MBW ternary complex involved in Arabidopsis trichome development. Amino acids 250-267 of GhMML4_D12 and the first and third WD40 repeat domains of GhWDR determine their interaction. GhWDR could rescue Arabidopsis ttg1 to its wild type, confirming its orthologous function in trichome development. Our findings shed more light towards understanding the key role of the MML and WD40 families in plants and in the improvement of cotton fiber production.

Personal growth initiative and posttraumatic stress among survivors of transportation accidents: Mixture modeling indicating changes in group membership over time.

The current study explored subgroups in reported personal growth initiative (PGI) and posttraumatic stress symptoms (PTSS) and examined the changes in class memberships among survivors of a transportation accident. Participants at Time 1 were 602 adults who reported directly experiencing a transportation accident within the past year (Mmonths = 6.36; SDmonths = 3.20). Of these participants, 171 adults completed the follow-up survey after 3 months (Time 2). Finite mixture modeling was conducted to identify the heterogeneity of PTSS in relation with PGI at each time point. At Time 1, a four-class model was the best-fitting model, and at Time 2, a three-class model was the best-fitting model. As hypothesized, when examined cross-sectionally, various subgroups were identified at each time point, finding subgroups with moderate to high levels of PGI but differing in their PTSS. However, when examining the longitudinal changes in class membership from Time 1 to Time 2, members of subgroups with higher PGI skills at Time 1 were more likely to be assigned to subgroups with lower PTSS at Time 2. The current study suggests a potential application of PGI skills in alleviating PTSS after a transportation accident and having a critical role in adjustment after hardship.

CELSR1 Promotes Neuroprotection in Cerebral Ischemic Injury Mainly Through the Wnt/PKC Signaling Pathway.

Cadherin epidermal growth factor (EGF) laminin G (LAG) seven-pass G-type receptor 1 (CELSR1) is a member of a special subgroup of adhesion G protein-coupled receptors. Although Celsr1 has been reported to be a sensitive gene for stroke, the effect of CELSR1 in ischemic stroke is still not known. Here, we investigated the effect of CELSR1 on neuroprotection, neurogenesis and angiogenesis in middle cerebral artery occlusion (MCAO) rats. The mRNA expression of Celsr1 was upregulated in the subventricular zone (SVZ), hippocampus and ischemic penumbra after cerebral ischemic injury. Knocking down the expression of Celsr1 in the SVZ with a lentivirus significantly reduced the proliferation of neuroblasts, the number of CD31-positive cells, motor function and rat survival and increased cell apoptosis and the infarct volume in MCAO rats. In addition, the expression of p-PKC in the SVZ and peri-infarct tissue was downregulated after ischemia/ reperfusion. Meanwhile, in the dentate gyrus of the hippocampus, knocking down the expression of Celsr1 significantly reduced the proliferation of neuroblasts; however, it had no influence on motor function, cell apoptosis or angiogenesis. These data indicate that CELSR1 has a neuroprotective effect on cerebral ischemia injury by reducing cell apoptosis in the peri-infarct cerebral cortex and promoting neurogenesis and angiogenesis, mainly through the Wnt/PKC pathway.

The Cumulative Risk Assessment of Hepatotoxic Chemicals: A Hepatic Histopathology Perspective.

The increased concern on the consequence of exposure to multiple chemical combinations has led national regulatory authorities to develop different concepts to conduct risk assessments on chemical mixtures. Pesticide residues were identified as "problem formulation" in the respective European regulations and in this context, the European Food and Safety Authority has suggested to group pesticidal active ingredients (AIs) into cumulative assessment groups (CAGs) based on the toxicological properties of each AI. One proposed CAG, on the liver, currently consists of 15 subgroups, each representing a specific hepatotoxic effect observed in toxicity studies. Dietary cumulative risk assessments would then have to be conducted assuming dose additivity of all members of each CAG subgroup. The purpose of this publication is to group AIs based upon the knowledge of the pathogenesis of liver effects to discriminate between primary end points (direct consequence of chemical interaction with a biological target) and secondary end points (which are a consequence of, or that arise out of, a previous pathological change). Focusing on the relevant primary end points strengthens and simplifies the selection of compounds for cumulative risk assessment regarding the liver and better rationalizes the basis for chemical grouping. Relevant dose additivity is to be expected at the level of the primary/leading pathological end points and not at the level of the secondary end points. We recognize, however, that special consideration is needed for substances provoking neoplasia, and this category is included in the group of primary end points for which chemicals inducing them are grouped for risk assessment. Using the pathological basis for defining the respective CAGs, 6 liver subgroups and 2 gallbladder/bile duct groups are proposed. This approach simplifies the cumulative assessment calculation without obviously affecting consumer safety.

Identification and Characterization of a β-N-Acetylhexosaminidase with a Biosynthetic Activity from the Marine Bacterium Paraglaciecola hydrolytica S66T.

β-N-Acetylhexosaminidases are glycoside hydrolases (GHs) acting on N-acetylated carbohydrates and glycoproteins with the release of N-acetylhexosamines. Members of the family GH20 have been reported to catalyze the transfer of N-acetylglucosamine (GlcNAc) to an acceptor, i.e., the reverse of hydrolysis, thus representing an alternative to chemical oligosaccharide synthesis. Two putative GH20 β-N-acetylhexosaminidases, PhNah20A and PhNah20B, encoded by the marine bacterium Paraglaciecola hydrolytica S66T, are distantly related to previously characterized enzymes. Remarkably, PhNah20A was located by phylogenetic analysis outside clusters of other studied β-N-acetylhexosaminidases, in a unique position between bacterial and eukaryotic enzymes. We successfully produced recombinant PhNah20A showing optimum activity at pH 6.0 and 50 °C, hydrolysis of GlcNAc β-1,4 and β-1,3 linkages in chitobiose (GlcNAc)2 and GlcNAc-1,3-β-Gal-1,4-β-Glc (LNT2), a human milk oligosaccharide core structure. The kinetic parameters of PhNah20A for p-nitrophenyl-GlcNAc and p-nitrophenyl-GalNAc were highly similar: kcat/KM being 341 and 344 mM−1·s−1, respectively. PhNah20A was unstable in dilute solution, but retained full activity in the presence of 0.5% bovine serum albumin (BSA). PhNah20A catalyzed the formation of LNT2, the non-reducing trisaccharide β-Gal-1,4-β-Glc-1,1-β-GlcNAc, and in low amounts the β-1,2- or β-1,3-linked trisaccharide β-Gal-1,4(β-GlcNAc)-1,x-Glc by a transglycosylation of lactose using 2-methyl-(1,2-dideoxy-α-d-glucopyrano)-oxazoline (NAG-oxazoline) as the donor. PhNah20A is the first characterized member of a distinct subgroup within GH20 β-N-acetylhexosaminidases.

Game theoretic models of sustainable management in marketing networks

Difference and differential Stackelberg games of opinion control on marketing networks are considered. The principal allocates financial resources to the firms for marketing purposes. It is supposed that the structure of a target audience described by a weighted directed graph is already determined in the stage of network analysis, and marketing control actions are applied only to the members of strong subgroups (opinion leaders). Conditions of homeostasis (phase constraints) which reflect the requirements of sustainable management are introduced additionally. The Stackelberg equilibria are found analytically. It is shown that the interests of the principal and the firms are completely compatible.

Dynamic SPICE-model of resource allocation in marketing networks

We consider a dynamic Stackelberg game theoretic model of the coordination of social and private interests (SPICE-model) of resource allocation in marketing networks. The dynamics of controlled system describes an interaction of the members of a target audience (basic agents) that leads to a change of their opinions (cost of buying the goods and services of firms competing on a market). An interaction of the firms (influence agents) is formalized as their differential game in strategic form. The payoff functional of each firm includes two terms: the summary opinion of the basic agents with consideration of their marketing costs (a common interest of all firms), and the income from investments in a private activity. The latter income is described by a linear function. The firms exert their influence not to all basic agents but only to the members of strong subgroups of the influence digraph (opinion leaders). The opinion leaders determine the stable final opinions of all members of the target audience. A coordinating principal determines the firms' marketing budgets and maximizes the summary opinion of the basic agents with consideration of the allocated resources. The Nash equilibrium in the game of influence agents and the Stackelberg equilibrium in a general hierarchical game of the principal with them are found. It is proved that the value of opinion of a basic agent is the same for all influence agents and the principal. It is also proved that the influence agents assign less resources for the marketing efforts than the principal would like.

The Host Range of Subgroup 16SrII-X Phytoplasma Extends to Globe Amaranth and Other Wild Plants in Saudi Arabia

In recent years, the number of plant hosts affected by peanut witches’-broom group (16SrII) phytoplasma in Saudi Arabia has increased at a concerning speed. Since 2015 symptoms resembling phytoplasma-related diseases have been reported in Al-Qassim region affecting the wild plants globe amaranth, amaranthus, black nightshade, and buckthorn. Except for globe amaranth, which showed flower deformations, the other plants showed witches’ broom and little leaves. All the symptomatic samples collected in this study were positive for phytoplasma using universal primers targeting the 16S rRNA-encoding gene. Sequence analysis identified the phytoplasma as a member of the 16SrII-X subgroup, originally described in Saudi Arabia by our group. This is the first report of globe amaranth, amaranthus, black nightshade, and buckthorn as phytoplasma hosts in Saudi Arabia, and the first report worldwide of globe amaranth as a phytoplasma host and buckthorn being affected by 16SrII phytoplasma group.

Diversity and Expression Patterns of MADS-Box Genes in Gnetum luofuense—Implications for Functional Diversity and Evolution

MADS-box transcription factors are essential mediators of the vegetative and reproductive development of seed plants. Although MADS-box genes have been extensively characterized in angiosperms, their functions are not well-understood in gymnosperms, especially the Gnetales, due to an ambiguous phylogeny of seed plants. Here, we performed a genome-wide search for MADS-box genes in Gnetum luofuense and found 11 Type I and 38 Type II MADS-box members (i.e. three MIKC* and 35 MIKCc genes). The relative abundance of the Type I Mα and Type II MIKCC subgroups (including the DEF/GLO and TM8-like genes) were mainly contributed by tandem duplications. Comparisons of the gene expression levels among members of the MIKCc subgroup reveal that the DEF/GLO-like genes and several TM8-like genes were exclusively expressed in reproductive organs, whereas TM3-like, StMADS11-like and other TM8-like genes exhibited a broad expression pattern in both vegetative and reproductive organs in G. luofuense. In addition, 14 Type II MIKCc genes were found in the stem transcriptome of Ephedra equisetina and we made an attempt to assess the homology to the MIKCc genes within Gnetales. The results of this study provide valuable information for understanding the phylogenies and functions of MADS-box genes in seed plants.

Ecological and social determinants of association and proximity patterns in the fission-fusion society of spider monkeys (Ateles geoffroyi).

Some social species exhibit high levels of fission-fusion dynamics (FFD) that improve foraging efficiency. In this study, we shed light on the way that FFD allows animal groups to cope with fluctuations in fruit availability. We explore the relative contribution of fruit availability and social factors like sex in determining association and proximity patterns in spider monkeys. We tested the influence of fruit availability and social factors on the association and proximity patterns using three-year data from a group of spider monkeys in the Yucatan Peninsula of Mexico. We identified subgroup members and estimated their Interindividual distances through instantaneous scan sampling. We evaluated fruit availability by monitoring the phenology of the 10 most important food tree species for spider monkeys in the study site. Social network analyses allowed us to evaluate association and proximity patterns in subgroups. We showed that association patterns vary between seasons, respond to changes in fruit availability, and are influenced by the sex of individuals, likely reflecting biological and behavioral differences between sexes and the interplay between ecological and social factors. In contrast, proximity patterns were minimally affected by changes in fruit availability, suggesting that social factors are more important than food availability in determining cohesion within subgroups.

Watch out! Insecure relationships affect vigilance in wild spider monkeys (Ateles geoffroyi)

Vigilance is used to monitor extra-group threats as well as risky group members. We examined whether relationship quality affects vigilance patterns of spider monkeys. We used focal animal sampling to collect data on social interactions and individual vigilance of all adults and subadults (N = 22) in a community of well-habituated Geoffroy’s spider monkeys living in the protected area of Otoch Ma’ax Yetel Kooh, Yucatan, Mexico. Through a principal component analysis of seven indices of social interactions, we previously obtained three components of relationship quality, reflecting the levels of compatibility, value, and security. Such components could differentially affect vigilance depending on whether vigilance is directed to extra-group threats or risky group members. We tested whether an individual’s vigilance was affected by (1) the mean level of compatibility, the mean level of value and the mean level of security across subgroup members; (2) the lowest level of compatibility, the lowest level of value, and the lowest level of security with any subgroup member; and (3) the mean level of compatibility, the mean level of value, and the mean level of security with neighbors (i.e., subgroup members within 5 m). We did not find evidence for any effect of compatibility and value; however, security did affect vigilance, as individuals were more vigilant when they had a less secure relationship with the subgroup member with the lowest level of security or with the average neighbor. Vigilance for monitoring group members is common in primate species. We examined whether the quality of social relationships with subgroup members and neighbors modulates vigilance in wild spider monkeys. We used three components of relationship quality (reflecting the levels of compatibility, value, and security) and predicted each component would affect vigilance depending on whether vigilance was directed to extra-group threats or risky group members. We found no evidence that compatibility and value affected vigilance. However, an increase in vigilance occurred when spider monkeys had a less secure relationship with (1) the subgroup member with the lowest level of security and (2) the average neighbor. Our results show monitoring risky group members is an important component of vigilance, especially in species facing low predation pressure.

Report of ‘Candidatus Phytoplasma hispanicum’ (16SrXIII-E) Associated with Cauliflower Stunt in São Paulo State, Brazil, and Balclutha hebe as Its Potential Vector

A cauliflower stunt disease associated with phytoplasmas occurs in crops of cauliflower (Brassica oleracea var. botrytis) in Sao Paulo state (SP), southeastern region of Brazil. The symptoms are characterized by stunting, extensive malformations of floral parts, leaf reddening, and vessel necrosis. 16SrIII-J and 16SrXV-A phytoplasmas have already been reported in association with this disease in this region (Canale and Bedendo 2013; Rappussi et al. 2012). Herein we report the involvement of 16SrXIII-E phytoplasma with cauliflower stunt disease and the presence of this bacteria in Balclutha hebe leafhopper. DNA was extracted using a DNeasy Plant Mini Kit (Qiagen, Hilden, Germany) from leaf veins of seven symptomatic and seven asymptomatic cauliflower samples collected in May 2008 from a farm located in Morungaba (SP, –22.882603, –46.755783). In addition, in an attempt to identify a possible vector for the phytoplasma, insects were captured using a sweep net from a cauliflower farm in Sorocaba (SP, –23.391314, –47.507474), where the disease occurred in high incidence levels (Rappussi et al. 2012). The most abundant leafhopper species collected with the net was identified as B. hebe Kirkaldy, 1900 (Hemiptera: Cicadellidae). DNA was also obtained from whole insects using the same extraction kit as we used for plants. Phytoplasma detection was performed with a nested-PCR assay using P1/Tint and R16F2n/R16R2 universal primers specific to the phytoplasma 16S rRNA gene (Lee et al. 1998; Smart et al. 1996). PCR products of the expected size (∼1.2 kb) were obtained from all of the symptomatic cauliflower but not from the collected symptomless samples. We amplified phytoplasma DNA from four out of 15 B. hebe specimens. Two plant amplicons and two leafhopper amplicons were sequenced (Macrogen, Seoul, Korea). Nucleotide sequence alignment revealed that 16S rDNA of the phytoplasma from cauliflower and insect samples shared ˃99% sequence similarity with Papaya apical curl necrosis phytoplasma, a member of the 16SrXIII-E subgroup and previously described by our group (Melo et al. 2013). Restriction fragment length polymorphism analysis using AluI, RsaI, KpnI, HpaII, MseI, HhaI, MboI, and BstUI restriction enzymes and in silico analysis using the iPhyClassifier online tool (Zhao et al. 2009) also allowed confirmation of the identification of the phytoplasma affecting cauliflower plant and leafhopper samples as member of the 16SrXIII-E subgroup (F = 1.00). A phylogenetic tree was generated with sequences of 16S rDNA of distinct subgroups affiliated with the 16SrXIII group, using the neighbor-joining method and 1,000 bootstrap replicates (MEGA software, Tamura et al. 2011), using Acholeplasma laidlawii as an outgroup. The phylogenetic analysis supported the identification of cauliflower and B. hebe phytoplasmas reported in this study as members of 16SrXIII-E subgroup. Sequences of the 16SrXIII-E phytoplasmas were deposited in GenBank as the accession JN818844 (Cauliflower stunt phytoplasma) and JN818843 (B. hebe phytoplasma). The 16SrXIII phytoplasma group (‘Candidatus Phytoplasma hispanicum’) is diverse and apparently restricted to the American continent, affecting a wide range of plant hosts (Davis et al. 2016). B. hebe is a polyphagous generalist species omnipresent in southern and south Brazil. It is reported as a putative vector for Xylella fastidiosa in plum orchards in south Brazil (Hickel et al. 2001). Also, this species was found in grasses within citrus rows in orchards in Sao Paulo, and one specimen was infected with 16SrIX phytoplasma (Marques et al. 2012). B. hebe was abundant within the cauliflower crops in both locations of this study, and its abundance along with our research results indicate that this leafhopper may play a role as a vector for 16SrXIII-E to cauliflower. However, more refined transmission assays employing phytoplasma and insects maintained in a laboratory are needed to prove B. hebe capacity as a phytoplasma vector. Here, we report ‘Ca. P. hispanicum’ strain as one of the associated phytoplasmas with cauliflower stunt disease in Brazil and B. hebe leafhopper as a putative vector.

Novel Parallel Heterogeneous Meta-Heuristic and Its Communication Strategies for the Prediction of Wind Power

Wind and other renewable energy protects the ecological environment and improves economic efficiency. However, it is difficult to accurately predict wind power because of the randomness and volatility of wind. This paper proposes a new parallel heterogeneous model to predict the wind power. Parallel meta-heuristic saves computation time and improves solution quality. Four communication strategies, which include ranking, combination, dynamic change and hybrid, are introduced to balance exploration and exploitation. The dynamic change strategy is to dynamically increase or decrease the members of subgroup to keep the diversity of the population. The benchmark functions show that the algorithms have excellent performance in exploration and exploitation. In the end, they are applied to successfully realize the prediction for wind power by training the parameters of the neural network.

Genomic organization of the chicken TCRβ locus originated by duplication of a Vβ segment combined with a trypsinogen gene

Based on the latest assembly of the red jungle fowl (Gallus gallus) genome sequence, we characterized the detailed genomic organization of the T cell receptor beta (TCRβ) locus of chicken. The chicken TCRβ locus spans approximately 210 kb, and is organized in a typical translocon organization as previously reported. Within this locus, a total of 16 germline Vβ gene segments were classified into three subgroups, containing 11, four, and one members, respectively. Phylogenetic analysis revealed that the chicken Vβ3.1 segment was homologous with the duck Vβ1 subgroup, and further clustered with Vβ segments from reptiles but not amphibians. We also identified nine protease serine 1 (PRSS1) and three protease serine 2 (PRSS2) genes, which were interspersed within the chicken TCRβ locus. Dot-plot analysis of the chicken TCRβ locus against itself revealed that the 5′ part of the locus had arisen through a series of tandem duplication events. The homology units were composed of one Vβ1 segment followed by a PRSS1 gene, or one Vβ2 segment followed by a PRSS2 gene. This duplication pattern, in which the Vβ segments and trypsinogen genes form a duplication unit, was unique to TCRβ loci of chicken and duck, but not observed in TCRβ loci of other tetrapods studied thus far. By analyzing the cloned TCRβ cDNA sequences, we found that the usage pattern of Vβ segments was consistent with the results of previous studies. These studies showed that members of the Vβ1 subgroup are preferentially utilized in V-D-J recombination. Furthermore, we found that the Vβ3.1 segment participated into V-D-J recombination, but at a very low frequency. The length distribution of the chicken complementarity-determining region 3β (CDR3β) showed a tendency similar to that observed for the duck.

Patients undergoing surgery for lumbar spinal stenosis experience unique courses of pain and disability: A group-based trajectory analysis.

ObjectiveIdentify patient subgroups defined by trajectories of pain and disability following surgery for degenerative lumbar spinal stenosis, and investigate the construct validity of the subgroups by evaluating for meaningful differences in clinical outcomes.MethodsWe recruited patients with degenerative lumbar spinal stenosis from 13 surgical spine centers who were deemed to be surgical candidates. Study outcomes (leg and back pain numeric rating scales, modified Oswestry disability index) were measured before surgery, and after 3, 12, and 24 months. Group-based trajectory models were developed to identify trajectory subgroups for leg pain, back pain, and pain-related disability. We examined for differences in the proportion of patients achieving minimum clinically important change in pain and disability (30%) and clinical success (50% reduction in disability or Oswestry score ≤22) 12 months from surgery.ResultsData from 548 patients (mean[SD] age = 66.7[9.1] years; 46% female) were included. The models estimated 3 unique trajectories for leg pain (excellent outcome = 14.4%, good outcome = 49.5%, poor outcome = 36.1%), back pain (excellent outcome = 13.1%, good outcome = 45.0%, poor outcome = 41.9%), and disability (excellent outcome = 30.8%, fair outcome = 40.1%, poor outcome = 29.1%). The construct validity of the trajectory subgroups was confirmed by between-trajectory group differences in the proportion of patients meeting thresholds for minimum clinically important change and clinical success after 12 postoperative months (p < .001).ConclusionSubgroups of patients with degenerative lumbar spinal stenosis can be identified by their trajectories of pain and disability following surgery. Although most patients experienced important reductions in pain and disability, 29% to 42% of patients were classified as members of an outcome trajectory subgroup that experienced little to no benefit from surgery. These findings may inform appropriate expectation setting for patients and clinicians and highlight the need for better methods of treatment selection for patients with degenerative lumbar spinal stenosis.

NLRX1 Is a Multifaceted and Enigmatic Regulator of Immune System Function.

Over the last decade, significant progress has been achieved in defining mechanisms underlying NLR regulation of immune system function. However, several NLR family members continue to defy our best attempts at characterization and routinely exhibit confounding data. This is particularly true for NLR family members that regulate signaling associated with the activation of other pattern recognition receptors. NLRX1 is a member of this NLR sub-group and acts as an enigmatic regulator of immune system function. NLRX1 has been shown to negatively regulate type-I interferon, attenuate pro-inflammatory NF-κB signaling, promote reactive oxygen species production, and modulate autophagy, cell death, and proliferation. However, the mechanism/s associated with NLRX1 modulation of these pathways is not fully understood and there are inconsistencies within the field. Likewise, it is highly likely that the full repertoire of biological functions impacted by NLRX1 are yet to be defined. Recent mouse studies have shown that NLRX1 significantly impacts a multitude of diseases, including cancer, virus infection, osteoarthritis, traumatic brain injury, and inflammatory bowel disease. Thus, it is essential that the underlying mechanism associated with NLRX1 function in each of these diseases be robustly defined. Here, we summarize the current progress in understanding mechanisms associated with NLRX1 function. We also offer insight into both unique and overlapping mechanisms regulated by NLRX1 that likely contribute to disease pathobiology. Ultimately, we believe that an improved understanding of NLRX1 will result in better defined mechanisms associated with immune system attenuation and the resolution of inflammation in a myriad of diseases.

PND16 PREFERENCES OF PATIENTS FOR FEATURES OF INJECTABLE, ORAL, AND INFUSED DISEASE-MODIFYING TREATMENTS FOR RELAPSE-REMITTING MULTIPLE SCLEROSIS

To quantify German multiple sclerosis (MS) patient preferences for attributes of disease-modifying treatments and examine subgroups with distinct preferences. Respondents with self-reported MS completed an online discrete-choice-experiment survey with a series of treatment-choice questions. Each hypothetical treatment had seven attributes with varying levels: years until disability progression; number of relapses in the next 10 years; mode of administration; dosing frequency; and risks of mild, moderate, and severe adverse events (AEs). Latent class analysis was used to estimate preferences for subgroups. Logit regression analysis was used to identify and describe likely members of the preference subgroups. Likely uptake of treatment profiles similar to available products was calculated by subgroup. There were two subgroups with distinct preferences amongst the 301 respondents. Subgroup 1 (43% of sample) was risk-focused and placed greatest importance (conditional on levels in the study) on minimizing risks of severe, moderate, and mild AEs, followed by avoiding relapses and delaying progression. Dosing frequency and mode were least important to this subgroup. Subgroup 2 (57% of sample) was efficacy- and severe AE-focused and placed the greatest importance on delaying progression and minimizing risks of severe AEs. The next most important attributes were risks of mild AEs and mode of administration. Dosing frequency and avoiding relapses were least important to this subgroup. Subgroups placed different relative importances on different treatment attributes. Decreasing the severe AE risk from 7% to 0% was 3.1 times as important as increasing the delay in progression from 2 years to 8 years for the risk-focused group. In contrast, for the efficacy-focused group, this delay in progression was 1.4 times more important than this risk reduction. Understanding the preferences of different patients will enable shared-decision making between physicians and patients, which may improve treatment satisfaction and adherence.

Do elites matter in Russian foreign policy? The gap between self-perception and influence

ABSTRACTThis article analyzes the findings of the Survey of Russian Elites from the perspective of Russian elites’ perceptions of their individual and group influence on Russian foreign policy. In the current Russian elite structure, state enterprise managers, executive branch officials, and military/security officers are far more influential than members of other sub-groups when it comes to foreign policy. However, the survey results show that despite being members of the elite, respondents in all sub-groups generally found their ability to influence foreign policy decisions to be quite limited. That being said, the data show that representatives of less influential elite sub-groups are more confident about their impact on the decision-making process than representatives of more influential elite sub-groups. As such, there is a gap between elite sub-groups’ perception of their influence and their actual level of individual and group influence on Russian foreign policy. The article discusses various manifestations of this gap, as well as possible causes and implications.

179. Predictors of clinical outcome following surgery for lumbar spinal stenosis: a study of postoperative pain and disability trajectories

BACKGROUND CONTEXT On average, patients experience important reductions in pain and disability following surgery for degenerative lumbar spinal stenosis (LSS). However, variability in the postoperative course of symptoms suggests many patients do not fit the average symptom trajectory. PURPOSE To identify patient subgroups defined by trajectories of pain and disability following surgery for LSS and investigate the construct validity of the subgroups by evaluating meaningful differences in clinical outcomes. Identify predictors of belonging to the poor outcomes subgroup for disability, leg pain and back pain. STUDY DESIGN/SETTING Retrospective analysis of prospectively collected data. PATIENT SAMPLE Patients with LSS were recruited from 13 surgical spine centers participating in the Canadian Spine Outcomes and Research Network registry. OUTCOME MEASURES Leg and back pain numeric rating scales and the modified Oswestry disability index were measured before surgery and at 3, 12, and 24 months following surgery. METHODS Patients were fit into pain and disability trajectory subgroups with group-based trajectory modeling. Differences in the proportion of patients achieving minimum clinically important change in pain and disability (30%) and clinical success (50% reduction in disability or Oswestry score ≤22) were examined. Generalized linear mixed models adjusted for age and sex, were used to identify associations between subgroup membership and preoperative demographic, clinical history, health status and surgical factors. The subgroup with excellent outcomes was used as the reference group; associations were reported with relative risk ratios (RR). RESULTS The group-based trajectory models identified 3 unique pain trajectories each (excellent, fair and poor) for leg pain, back pain and disability. Depending on outcome 29% to 42% of patients were classified as members of an outcome trajectory subgroup that experienced little to no benefit from surgery. The construct validity of the trajectory subgroups was supported by differences in the proportion of patients meeting thresholds for minimum clinically important change and clinical success (p CONCLUSIONS The percentage of patients with poor outcomes highlights the need for better methods of treatment selection for patients with LSS. The predictors of having poor outcomes suggests it is time to look beyond pathology/surgical factors only and include mental health variables as an integral part of the surgical decision-making process in an effort to avoid patients at increased risk for surgical failure. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.