Inactivation of a peroxiredoxin by hydrogen peroxide is critical for thioredoxin-mediated repair of oxidized proteins and cell survival.

Eukaryotic 2-Cys peroxiredoxins (Prx) are abundant antioxidant enzymes whose thioredoxin peroxidase activity plays an important role in protecting against oxidative stress, aging, and cancer. Paradoxically, this thioredoxin peroxidase activity is highly sensitive to inactivation by peroxide-induced Prx hyperoxidation. However, any possible advantage in preventing Prx from removing peroxides under oxidative stress conditions has remained obscure. Here we demonstrate that, in cells treated with hydrogen peroxide, the Prx Tpx1 is a major substrate for thioredoxin in the fission yeast Schizosaccharomyces pombe and, as such, competitively inhibits thioredoxin-mediated reduction of other oxidized proteins. Consequently, we reveal that the hyperoxidation of Tpx1 is critical to allow thioredoxin to act on other substrates ensuring repair of oxidized proteins and cell survival following exposure to toxic levels of hydrogen peroxide. We conclude that the inactivation of the thioredoxin peroxidase activity of Prx is important to maintain thioredoxin activity and cell viability under oxidative stress conditions.

Bright G-Quadruplex Nanostructures Functionalized with Porphyrin Lanterns.

The intricate arrangement of numerous and closely placed chromophores on nanoscale scaffolds can lead to key photonic applications ranging from optical waveguides and antennas to signal-enhanced fluorescent sensors. In this regard, the self-assembly of dye-appended DNA sequences into programmed photonic architectures is promising. However, the dense packing of dyes can result in not only compromised DNA assembly (leading to ill-defined structures and precipitates) but also to essentially nonfluorescent systems (due to π-π aggregation). Here, we introduce a two-step "tether and mask" strategy wherein large porphyrin dyes are first attached to short G-quadruplex-forming sequences and then reacted with per-O-methylated ß-cyclodextrin (PMßCD) caps, to form supramolecular synthons featuring the porphyrin fluor fixed into a masked porphyrin lantern (PL) state, due to intramolecular host-guest interactions in water. The PL-DNA sequences can then be self-assembled into cyclic architectures or unprecedented G-wires tethered with hundreds of porphyrin dyes. Importantly, despite the closely arrayed PL units (∼2 nm), the dyes behave as bright chromophores (up to 180-fold brighter than the analogues lacking the PMßCD masks). Since other self-assembling scaffolds, dyes, and host molecules can be used in this modular approach, this work lays out a general strategy for the bottom-up aqueous self-assembly of bright nanomaterials containing densely packed dyes.

Continuous control of flagellar gene expression by the σ28-FlgM regulatory circuit in Salmonella enterica.

The flagellar genes in Salmonella enterica are expressed in a temporal hierarchy that mirrors the assembly process itself. The σ(28)-FlgM regulatory circuit plays a key role in controlling this temporal hierarchy. This circuit ensures that the class 3 genes are expressed only when the hook-basal body (HBB), a key intermediate in flagellar assembly, is complete. In this work, we investigated the role of the σ(28)-FlgM regulatory circuit in controlling the timing and magnitude of class 3 gene expression using a combination of mathematical modelling and experimental analysis. Analysis of the model predicted that this circuit continuously controls class 3 gene expression in response to HBB abundance. We experimentally validated these predictions by eliminating different components of the σ(28)-FlgM regulatory system and also by rewiring the transcriptional hierarchy. Based on these results, we conclude that the σ(28)-FlgM regulatory circuit continuously senses the HBB assembly process and regulates class 3 gene expression and possibly flagellar numbers in response.

Intraoperative Proximal Tibia Periprosthetic Fractures in Primary Total Knee Arthroplasty.

Intraoperative fracture of the proximal tibia is a rare complication of total knee arthroplasty (TKA) with few studies available reporting risk factors or prognosis. A review of our prospective joint registry was performed to determine the incidence and associated risk factors of intraoperative tibia fractures during primary TKA; 14,966 TKAs of all manufacturers were performed with 9 intraoperative tibia fractures. All fractures occurred in a single TKA design. There were 8,155 TKAs of this design performed with a fracture incidence of 0.110%. All but one fracture occurred on the medial tibial plateau, and all but one occurred during preparation of the tibia with keel punching. A control group of 75 patients (80 knees) with the same TKA design were randomly selected. Baseplates size 3 or smaller were less likely to experience an intraoperative fracture (odds ratio [OR]: 0.864, 95% confidence interval [CI]: 0.785-0.951), as were knees with a polyethylene insert thickness of 13 mm or larger (OR: 0.882, 95% CI: 0.812-0.957). Fractures were treated with a variety of different methods, but every patient had at least one screw placed and most (67%) had postoperative weight-bearing restrictions. At final follow-up, there were no cases of nonunion, component subsidence, or need for reoperation. Intraoperative tibia fractures are a rare complication of this TKA design at 0.11%. Knees with baseplates of size ≤3 and polyethylene thickness ≥13 mm were less likely to experience intraoperative fracture. These findings may be related to the depth of tibial resection, requiring the use of a thicker polyethylene insert, and a change in the keel width in implants size 4 or larger. No fracture patients required reoperation.

It's not WEIRD, it's WRONG: when researchers overlook uNderlying genotypes, they will not detect universal processes.

We dispute Henrich et al.'s analysis of cultural differences at the level of a narrow behavioral-expression for assessing a universalist argument. When Researchers Overlook uNderlying Genotypes (WRONG), they fail to detect universal processes that generate observed differences in expression. We reify this position with our own cross-cultural research on self-enhancement and self-esteem.

Thinking and feeling in the People's Republic of China: testing the generality of the "laws of emotion".

Cognitive theories of emotion assert that emotional reactions to events depend on the manner in which events are interpreted and appraised. From this perspective, the same outcome can produce different emotions. For example, a score of 85% on a test can evoke positive feelings if it is considered a success or negative feelings if it is considered a failure. Among the various appraisal dimensions that have been identified, causal attributions are thought to play a particularly influential role in shaping emotional reactions to various events. For example, success can evoke pride if it is attributed to high ability, gratitude if it is attributed to help from others, relief if it is attributed to a stroke of good fortune, or guilt if it is attained fraudulently or at the expense of others. These cognitive-affective linkages are thought to be universal. In this paper, we report two studies that tested the cross-cultural generality of some of these assumptions. In Study 1, participants from the People's Republic of China were led to succeed or fail on an (alleged) test of their intelligence and creativity. Consistent with previous findings with Western samples, attributions to ability predicted participants' emotional reactions to their test performance, with high ability attributions linked to greater pride following success. In Study 2, we extended these findings with American and Chinese participants, using a different experimental manipulation of success and failure, and a measure of attributions to effort. For both cultural groups, attributions to ability (but not attributions to effort) predicted greater emotional reactions to success. We conclude that attribution-emotion linkages have cross-cultural validity, and that pride is maximized when success is attributed to high ability.

The rate of protein secretion dictates the temporal dynamics of flagellar gene expression.

Flagellar gene expression is temporally regulated in response to the assembly state of the growing flagellum. The key mechanism for enforcing this temporal hierarchy in Salmonella enterica serovar Typhimurium is the sigma(28)-FlgM checkpoint, which couples the expression of the late flagellar (P(class3)) genes to the completion of the hook-basal body. This checkpoint is triggered when FlgM is secreted from the cell. In addition to the sigma(28)-FlgM checkpoint, a number of other regulatory mechanisms respond to the secretion of late proteins. In this work, we examined how middle (P(class2)) and late (P(class3)) gene expression is affected by late protein secretion. Dynamic analysis of flagellar gene expression identified a novel mechanism where induction of P(class2) activity is delayed either when late protein secretion is abolished or when late protein secretion is increased. Using a number of different approaches, we were able to show that this mechanism did not involve any known flagellar regulator. Furthermore, the changes in P(class2) activity were not correlated with the associated changes in P(class3) activity, which was found to be proportional to late protein secretion rates. Our data indicate that both P(class2) and P(class3) promoters are continuously regulated in response to assembly and late protein secretion rates. These results suggest that flagellar regulation is more complex than previously thought.

FliZ Is a posttranslational activator of FlhD4C2-dependent flagellar gene expression.

Flagellar assembly proceeds in a sequential manner, beginning at the base and concluding with the filament. A critical aspect of assembly is that gene expression is coupled to assembly. When cells transition from a nonflagellated to a flagellated state, gene expression is sequential, reflecting the manner in which the flagellum is made. A key mechanism for establishing this temporal hierarchy is the sigma(28)-FlgM checkpoint, which couples the expression of late flagellar (P(class3)) genes to the completion of the hook-basal body. In this work, we investigated the role of FliZ in coupling middle flagellar (P(class2)) gene expression to assembly in Salmonella enterica serovar Typhimurium. We demonstrate that FliZ is an FlhD(4)C(2)-dependent activator of P(class2)/middle gene expression. Our results suggest that FliZ regulates the concentration of FlhD(4)C(2) posttranslationally. We also demonstrate that FliZ functions independently of the flagellum-specific sigma factor sigma(28) and the filament-cap chaperone/FlhD(4)C(2) inhibitor FliT. Furthermore, we show that the previously described ability of sigma(28) to activate P(class2)/middle gene expression is, in fact, due to FliZ, as both are expressed from the same overlapping P(class2) and P(class3) promoters at the fliAZY locus. We conclude by discussing the role of FliZ regulation with respect to flagellar biosynthesis based on our characterization of gene expression and FliZ's role in swimming and swarming motility.

Management and Prevention of Intraoperative Acetabular Fracture in Primary Total Hip Arthroplasty.

Intraoperative acetabular fracture (IAF) is a rare complication of primary total hip arthroplasty (THA). Known risk factors include poor bone stock, underreaming of the acetabular bed, and use of elliptic components. There is a paucity of literature on risk factors, treatment strategies, and outcomes of this potentially devastating complication. We studied the incidence of IAF in primary THA at our high-volume institution. We reviewed 21,519 primary THA cases and identified 16 patients (16 hips) with IAFs. Mean follow-up was 4 years (range, 0-10 years). Implant data were recorded, and acetabular components were identified as elliptic modular or hemispheric modular. The institution's IAF rate was 0.0007%. All IAFs were associated with uncemented acetabular components. Sixty-nine percent of the fractures were not appreciated during surgery. All posterior column fractures required operative intervention in the immediate or early (<3 months) postoperative period. Compared with anterior column fractures, posterior column fractures were associated with acetabular component instability and need for additional surgery. In this article, we also present strategies for managing and preventing IAF in primary THA. This rare fracture requires prompt recognition and often necessitates aggressive management. More study is needed to determine how to better manage IAFs.

Sequential analysis of child pain behavior and maternal responses: an observational study.

This laboratory-based study examined lagged associations between child pain behavior and maternal responses as a function of maternal catastrophizing (CAT). Mothers completed the parent version of the Pain Catastrophizing Scale. Children participated in a validated water ingestion procedure to induce abdominal discomfort with mothers present. Video recordings of their interactions were edited into 30-second segments and coded by 2 raters for presence of child pain behavior, maternal solicitousness, and nontask conversation. Kappa reliabilities ranged from 0.83 to 0.95. Maternal CAT was positively associated with child pain behavior and maternal solicitousness, P values <0.05. In lagged analyses, child pain behavior during a given segment (T) was positively associated with child pain behavior during the subsequent segment (T + 1), P <0.05. Maternal CAT moderated the association between (1) child pain behavior at T and maternal solicitousness at T + 1, and (2) solicitousness at T and child pain behavior at T + 1, P values <0.05. Mothers higher in CAT responded solicitously at T + 1 irrespective of their child's preceding pain behavior, and their children exhibited pain behavior at T + 1 irrespective of the mother's preceding solicitousness. Mothers lower in CAT were more likely to respond solicitously at T + 1 after child pain behavior, and their children were more likely to exhibit pain behavior at T + 1 after maternal solicitousness. These findings indicate that high CAT mothers and their children exhibit inflexible patterns of maternal solicitousness and child pain behavior, and that such families may benefit from interventions to decrease CAT and develop more adaptive responses.

Trait aggressiveness and situational provocation: a test of the traits as situational sensitivities (TASS) model.

In this article, the authors propose and test an interactionist model of personality functioning. The model maintains that many traits function in a threshold-like manner, such that less situational strength is needed to evoke a trait-relevant response in people who are high on the trait than in those who are low on the trait. Because of these different sensitivities, people who are high on a trait are more reactive to moderate provocation than are those who are low on a trait, but the opposite is true when strong provocation is compared to moderate provocation. Three studies are reported showing how the model can be used to understand the nature of aggression.

Pain catastrophizing predicts verbal expression among children with chronic pain and their mothers.

This study examined intra- and inter-personal associations between pain catastrophizing and verbal expression in 70 children with recurrent abdominal pain and their mothers. Participants independently completed the Pain Catastrophizing Scale. Mothers and children then talked about the child's pain. Speech was categorized using a linguistic analysis program. Catastrophizing was positively associated with the use of negative emotion words by both mothers and children. In addition, mothers' catastrophizing was positively associated with both mothers' and children's anger word usage, whereas children's catastrophizing was inversely associated with mothers' anger word usage. Findings extend the literature on behavioral and interpersonal aspects of catastrophizing.

Femoral Component Revision of Total Hip Arthroplasty.

Modern primary total hip arthroplasty (THA) is among the most successful operations in medicine. It has been a consistently effective treatment for end-stage osteoarthritis of the hip. With the increasing number of primary THA procedures being performed and the decreasing age of patients undergoing the procedure, there is an inevitable associated increase in revision burden for arthroplasty surgeons. Revision THA is most often indicated for instability, aseptic loosening, osteolysis, infection, periprosthetic fracture, component malposition, and catastrophic implant failure. Understanding the etiology of THA failure is essential for guiding clinical decision making. Femoral component revision presents a complex challenge to the arthroplasty surgeon because of modern implant design as well as bone loss in the proximal femur. Thorough patient evaluation, defect classification, and well-executed surgical reconstruction based on comprehensive preoperative planning may determine the postoperative results. Knowledge of various reconstructive options and the indications for each is necessary to achieve a successful outcome. This article highlights the most common indications for revision after THA and offers recommendations for how to approach revision of the femoral component. Specifically, the authors review preoperative assessment, common classification systems for femoral deficiency, techniques for component extraction, and modalities of femoral component fixation. [Orthopedics. 2016; 39(6):e1129-e1139.].

A Quantitative Diffuse Reflectance Imaging (QDRI) System for Comprehensive Surveillance of the Morphological Landscape in Breast Tumor Margins.

In an ongoing effort to address the clear clinical unmet needs surrounding breast conserving surgery (BCS), our group has developed a next-generation multiplexed optical-fiber-based tool to assess breast tumor margin status during initial surgeries. Specifically detailed in this work is the performance and clinical validation of a research-grade intra-operative tool for margin assessment based on diffuse optical spectroscopy. Previous work published by our group has illustrated the proof-of-concept generations of this device; here we incorporate a highly optimized quantitative diffuse reflectance imaging (QDRI) system utilizing a wide-field (imaging area = 17 cm(2)) 49-channel multiplexed fiber optic probe, a custom raster-scanning imaging platform, a custom dual-channel white LED source, and an astronomy grade imaging CCD and spectrograph. The system signal to noise ratio (SNR) was found to be greater than 40 dB for all channels. Optical property estimation error was found to be less than 10%, on average, over a wide range of absorption (µa = 0-8.9 cm(-1)) and scattering (µs' = 7.0-9.7 cm(-1)) coefficients. Very low inter-channel and CCD crosstalk was observed (2% max) when used on turbid media (including breast tissue). A raster-scanning mechanism was developed to achieve sub-pixel resolution and was found to be optimally performed at an upsample factor of 8, affording 0.75 mm spatially resolved diffuse reflectance images (λ = 450-600 nm) of an entire margin (area = 17 cm(2)) in 13.8 minutes (1.23 cm(2)/min). Moreover, controlled pressure application at the probe-tissue interface afforded by the imaging platform reduces repeated scan variability, providing <1% variation across repeated scans of clinical specimens. We demonstrate the clinical utility of this device through a pilot 20-patient study of high-resolution optical parameter maps of the ratio of the ß-carotene concentration to the reduced scattering coefficient. An empirical cumulative distribution function (eCDF) analysis is used to reduce optical property maps to quantitative distributions representing the morphological landscape of breast tumor margins. The optimizations presented in this work provide an avenue to rapidly survey large tissue areas on intra-operative time scales with improved sensitivity to regions of focal disease that may otherwise be overlooked.

Use of an electronic nose system for diagnoses of urinary tract infections.

The use of volatile production patterns produced by bacterial contaminants in urine samples were examined using electronic nose technology. In two experiments 25 and 45 samples from patients were analysed for specific bacterial contaminants using agar culture techniques and the major UTI bacterial species identified. These samples were also analysed by incubation in a volatile generation test tube system for 4-5 h. The volatile production patterns were then analysed using an electronic nose system with 14 conducting polymer sensors. In the first experiment analysis of the data using a neural network (NN) enabled identification of all but one of the samples correctly when compared to the culture information. Four groups could be distinguished, i.e. normal urine, Escherichia coli infected, Proteus spp. and Staphylococcus spp. In the second experiment it was again possible to use NN systems to examine the volatile production patterns and identify 18 of 19 unknown UTI cases. Only one normal patient sample was mis-identified as an E. coli infected sample. Discriminant function analysis also differentiated between normal urine samples, that infected with E. coli and with Staphylococcus spp. This study has shown the potential for early detection of microbial contaminants in urine samples using electronic nose technology for the first time. These findings will have implications for the development of rapid systems for use in clinical practice.

Seeking self-evaluative feedback: the interactive role of global self-esteem and specific self-views.

People who verify a negative self-view expose themselves to criticism and rejection. Because people with low global self-esteem are hurt more by negative feedback than are people with high global self-esteem, the authors predicted that they would be less apt to verify a negative self-view in a more specific domain. Three investigations found support for this hypothesis. In all 3 investigations, high self-esteem participants sought (or tended to seek) self-verifying feedback, even if it was negative, but low self-esteem participants sought (or tended to seek) positive feedback, even if it was nonself-verifying. These findings show that low self-esteem people are especially concerned with self-protection and that global self-esteem and specific self-views interact to guide people's responses to self-evaluative feedback.

Do people with low self-esteem really want to feel better? Self-esteem differences in motivation to repair negative moods.

This research examined the hypothesis that people with low self-esteem (LSE) are less motivated than people with high self-esteem (HSE) to repair their negative moods. In Study 1, participants completed diaries in response to either a success or a failure in their everyday lives. Participants described what they intended to do next and the reasons behind those plans. After failure, fewer LSE than HSE participants expressed a goal to improve their mood. A follow-up investigation (Study 2) suggested that this difference was not due to a self-esteem difference in knowledge of mood repair strategies. In Study 3, after undergoing a negative mood induction, fewer LSE than HSE participants chose to watch a comedy video, even though both groups believed the comedy video would make them happy. Studies 4 and 5 explored possible reasons why LSE people are less motivated than HSE people to repair their negative moods.

A peroxiredoxin promotes H2O2 signaling and oxidative stress resistance by oxidizing a thioredoxin family protein.

H2O2 can cause oxidative damage associated with age-related diseases such as diabetes and cancer but is also used to initiate diverse responses, including increased antioxidant gene expression. Despite significant interest, H2O2-signaling mechanisms remain poorly understood. Here, we present a mechanism for the propagation of an H2O2 signal that is vital for the adaptation of the model yeast, Schizosaccharomyces pombe, to oxidative stress. Peroxiredoxins are abundant peroxidases with conserved antiaging and anticancer activities. Remarkably, we find that the only essential function for the thioredoxin peroxidase activity of the Prx Tpx1(hPrx1/2) in resistance to H2O2 is to inhibit a conserved thioredoxin family protein Txl1(hTxnl1/TRP32). Thioredoxins regulate many enzymes and signaling proteins. Thus, our discovery that a Prx amplifies an H2O2 signal by driving the oxidation of a thioredoxin-like protein has important implications, both for Prx function in oxidative stress resistance and for responses to H2O2.

Understanding the better than average effect: motives (still) matter.

People evaluate themselves more positively than they evaluate most other people. Although this better than average (BTA) effect was originally thought to represent a motivated bias, several cognitively oriented theorists have questioned whether this is the case. In support of a motivational model, the author reports five studies showing that the BTA effect is stronger for important attributes than unimportant ones (all five studies) and that once attribute importance is taken into account, the effect occurs when self-evaluations are compared with a single peer (Study 2) and when self is specified as the referent rather than the target (Study 4). Finally, Study 5 shows that the BTA effect increases in magnitude after participants experience a threat to their feelings of self-worth. Collectively, these findings establish that motivational processes underlie the BTA effect.