"Anxiebo", placebo, and postoperative pain

Background

Surgical treatment and its consequences expose patients to stress, and here we investigated the importance of the psychological component of postoperative pain based on reports in the clinical literature.

Discussion

Postoperative pain remains a significant clinical problem. Increased pain intensity with increased demand for opioid medication, and/or a relative unresponsiveness to pain treatment was reported both when the analgesia was administered by means of conventional nurse injection regimes and patient-controlled analgesia (PCA). Both the quality of the analgesia, and the sensitivity of postoperative models for assessing analgesic efficacy could be significantly influenced. The findings could be explained by increased penetration of an algesic anxiety-related nocebo influence (which we chose to call "anxiebo") relative to its analgesic placebo counterpart. To counteract this influence, the importance of psychological effects must be acknowledged, and doctors and attending nurses should focus on maintaining trustful therapist-patient relationships throughout the treatment period. The physical mechanism of anxiebo should be further explored, and those at risk for anxiebo better characterized. In addition, future systemic analgesic therapies should be directed towards being prophylactic and continuous to eliminate surgical pain as it appears in order to prevent the anxiebo effect. Addressing anxiebo is the key to developing reproducible models for measuring pain in the postoperative setting, and to improving the accuracy of measurements of the minimum effective analgesic concentration.

Summary

Anxiebo and placebo act as counterparts postoperatively. The anxiebo state may impair clinical analgesia and reduce the sensitivity of analgesic trials. Ways to minimize anxiebo are discussed.     

Two types of endothelial cells in the heart of platyfish (Poeciliidae: Teleostei)

The present study describes two structurally and functionally different endothelial cell types in the heart of platyfish (Xiphophorus maculatus), which reflect adaptions to two quite unlike environments in this organ. The endothelial layers on the wall and valves of the ventricular apertures come in contact with only a small amount of the blood volume and have not evolved any blood cleaning abilities. These endothelial layers mainly protect the underlying tissue against the strain caused by a high blood flow. In contrast, the endothelium on the muscle trabeculae within the heart wall comes in contact with a large part of the blood volume at a low strain and have evolved structural features which make them highly efficient as blood cleaning tissue in this species.     

Mitogen-inducible gene 6 is an endogenous inhibitor of HGF/Met-induced cell migration and neurite growth

Hepatocyte growth factor (HGF)/Met signaling controls cell migration, growth and differentiation in several embryonic organs and is implicated in human cancer. The physiologic mechanisms that attenuate Met signaling are not well understood. Here we report a mechanism by which mitogen-inducible gene 6 (Mig6; also called Gene 33 and receptor-associated late transducer) negatively regulates HGF/Met-induced cell migration. The effect is observed by Mig6 overexpression and is reversed by Mig6 small interfering RNA knock-down experiments; this indicates that endogenous Mig6 is part of a mechanism that inhibits Met signaling. Mig6 functions in cells of hepatic origin and in neurons, which suggests a role for Mig6 in different cell lineages. Mechanistically, Mig6 requires an intact Cdc42/Rac interactive binding site to exert its inhibitory action, which suggests that Mig6 acts, at least in part, distally from Met, possibly by inhibiting Rho-like GTPases. Because Mig6 also is induced by HGF stimulation, our results suggest that Mig6 is part of a negative feedback loop that attenuates Met functions in different contexts and cell types.     

Breeding success, nestling diet and parental care in the White-backed WoodpeckerDendrocopos leucotos

In western Norway, pairs of White-backed Woodpecker breeding in coastal areas (<2 km from the sea) started egg laying earlier than pairs in inland areas (2–15 km from the sea). Laying was earlier in years when the ambient temperature was higher during the pre-laying period. About half of 69 pairs studied started laying within the period 25–30 April over the 10 study years. Clutch size ( = 4.0 eggs) and breeding success values (fledglings per egg; = 0.63) did not differ between years. The mean number of fledglings per nest was 2.4. The mean body mass of fledglings differed between years and were negatively correlated with the laying date. Fledgling mass differed between sexes (males = 87.8g, females = 84.2g), and both sexes were heavier in coastal than in inland areas. The mean hourly feeding rate of nestlings increased with nestling age, but feeding rate per nestling did not vary with nestling number. The nestling food was mainly comprised by wood-living beetle larvae ( = 72% by dry mass). It is suggested that breeding success is related to territorial quality, which, in turn, strongly influences female quality.

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Zusammenfassung In Westnorwegen beginnen Weißrückenspechte, die an der Küste brüten, eher mit der Eiablage als Paare im Inland (>2 km von der Küsten entfernt). Höhere Lufttemperaturen in der Vorlegezeit begünstigten frühere Eiablage. Mehr als die Hälfte der 69 untersuchten Paare begannen innerhalb von 10 Jahren zwischen 25. und 30. April mit der Eiablage. Gelegegröße ( = 4,0 Eier) und Bruterfolg (flügge Junge pro Ei; = 0,63) unterschieden sich nicht in einzelnen Jahren. Pro Nest flogen 2,4 Junge aus. Die mittlere Körpermasse der flüggen Jungvögel war mit dem Datum der Eiablage negativ korreliert. Flügge Männchen waren etwas schwerer als gleichalte Weibchen ( 87,9, 84,2 g); beide Geschlechter waren in Küstengebieten schwerer als im Inland. Die mittlere Fütterungsrate pro Stunde stieg mit dem Alter der Nestlinge, veränderte sich aber nicht mit der Zahl der Nestlinge. Die Nestlingsnahrung bestand vor allem aus holzbewohnenden Käferlarven ( = 72% der Trockenmasse). Vermutlich hängt der Bruterfolg mit der Qualität des Brutreviers zusammen, die wiederum vor allem die Kondition des Weibchens bestimmt.

     

The Prognostic Significance of Wnt-5a Expression in Primary Breast Cancer Is Extended to Premenopausal Women

Wnt-5a protein expression in primary tumors from unselected breast cancer patients has revealed a tumor suppressive function of the protein. However, in vitro experiments on human breast cancer cells have reported contradictory results, indicating both a tumor suppressive and promoting functions of Wnt-5a. This could be due to various functions of Wnt-5a in different subgroups of patients. The unselected cohorts analyzed to date for Wnt-5a protein expression contained few premenopausal patients. The aim of the present investigation was to evaluate the prognostic significance of Wnt-5a protein expression in a cohort of premenopausal women with comprehensive data on biomarkers, molecular subtypes and long-term outcome. In a randomized trial of adjuvant tamoxifen versus no adjuvant treatment, 564 premenopausal primary breast cancer patients were included. The median follow-up time was 14 years. A tumor tissue array was constructed and 361 samples were evaluated for Wnt-5a reactivity by immunohistochemistry. The primary end-point was recurrence-free survival. Wnt-5a protein expression was reduced or lost in 146/361 of tumors and correlated to younger age, estrogen receptor (ER) negativity and triple-negative phenotype. Wnt-5a was a prognostic factor in the whole cohort (p = 0.003). In patients with ER-positive tumors, Wnt-5a was an independent positive prognostic marker (HR 0.51 95% CI: 0.33–0.78 p = 0.002) and HER2 a negative prognostic marker (HR 2.84 95% CI: 1.51–5.31, p = 0.001) in a Cox multivariate analysis adjusted for standard prognostic markers and tamoxifen treatment. In the ER-negative subset, Wnt-5a added no prognostic information. In a subgroup analysis, Wnt-5a was significantly associated with better prognosis in patients with Luminal A tumors (p = 0.04). Conclusively, our results suggest that loss of Wnt-5a is a valuable prognostic marker in premenopausal breast cancer patients in particular in patients with ER-positive tumors and out-performed conventional prognostic factors in this subset of patients.     

Elevated [CO2] and growth temperature have a small positive effect on photosynthetic thermotolerance of Pinus taeda seedlings

Key message

Growth temperature had little effect on the response of net photosynthesis to high temperatures (up to 47 °C). On the other hand, elevated [CO ₂ ] increased net photosynthesis at high temperatures.

Abstract

We investigated whether Pinus taeda seedlings grown under elevated CO₂-concentration ([CO₂]) and temperature would be able to maintain positive net photosynthesis (A _net) longer than seedlings grown under ambient conditions when exposed to temperatures up to 47 °C. Additionally, we investigated whether a locally applied temperature increase would yield the same short-term gas exchange response to temperatures up to 47 °C as a naturally occurring latitudinal temperature increase of equal magnitude. Growth conditions were applied for 7 months (February to August) in treatment chambers constructed at two sites in the native range of P. taeda in the southern US. The sites were located 300 km apart along a north–south axis with a natural temperature difference of 2.1 °C. Seedlings were grown under ambient temperature and [CO₂] conditions at both sites. At the northern site, we also applied a temperature increase of 2 °C (T _E), ensuring that this treatment equalled the mean temperature at the southern site. Additionally, at the northern site, we applied a treatment of elevated [CO₂] (C _E). Gas exchange was measured on all plants in walk-in environmentally controlled chambers. Under C _E, there was no difference in A _net of seedlings grown in ambient or ambient +2 °C temperatures at any measurement temperature, while differences were present under ambient [CO₂]. Furthermore, A _net was higher under C _E than under ambient [CO₂]. At 47 °C, A _net was negative in all seedlings except those in the C _E and ambient temperature treatment combination. Seedlings at the northern site in the T _E treatment showed no significant differences in A _net compared with seedlings grown at ambient temperature at the southern site, indicating that the plants responded equally to a manipulated temperature increase and a latitudinal increase in temperature. Our results suggest that elevated [CO₂] increases photosynthetic thermotolerance at high temperature (>41 °C), but this effect diminishes as temperature increases further. Temperature manipulations could provide accurate information on the effect of latitudinal differences in temperature on leaf gas exchange of P. taeda.     

OLS Dialog: An open-source front end to the Ontology Lookup Service

Background  

With the growing amount of biomedical data available in public databases it has become increasingly important to annotate data in a consistent way in order to allow easy access to this rich source of information. Annotating the data using controlled vocabulary terms and ontologies makes it much easier to compare and analyze data from different sources. However, finding the correct controlled vocabulary terms can sometimes be a difficult task for the end user annotating these data.     

Meiotic regulation of the CDK activator RINGO/Speedy by ubiquitin-proteasome-mediated processing and degradation

Xenopus RINGO/Speedy (XRINGO) is a potent inducer of oocyte meiotic maturation that can directly activate Cdk1 and Cdk2. Here, we show that endogenous XRINGO protein accumulates transiently during meiosis I entry and then is downregulated. This tight regulation of XRINGO expression is the consequence of two interconnected mechanisms: processing and degradation. XRINGO processing involves recognition of at least three distinct phosphorylated recognition motifs by the SCF(betaTrCP) ubiquitin ligase, followed by proteasome-mediated limited degradation, resulting in an amino-terminal XRINGO fragment. XRINGO processing is directly stimulated by several kinases, including protein kinase A and glycogen synthase kinase-3beta, and may contribute to the maintenance of G2 arrest. On the other hand, XRINGO degradation after meiosis I is mediated by the ubiquitin ligase Siah-2, which probably requires phosphorylation of XRINGO on Ser 243 and may be important for the omission of S phase at the meiosis-I-meiosis-II transition in Xenopus oocytes.     

MassSorter: a tool for administrating and analyzing data from mass spectrometry experiments on proteins with known amino acid sequences

Background  

Proteomics is the study of the proteome, and is critical to the understanding of cellular processes. Two central and related tasks of proteomics are protein identification and protein characterization. Many small laboratories are interested in the characterization of a small number of proteins, e.g., how posttranslational modifications change under different conditions.