A Hydrothermal-Sedimentary Context for the Origin of Life.

Critical to the origin of life are the ingredients of life, of course, but also the physical and chemical conditions in which prebiotic chemical reactions can take place. These factors place constraints on the types of Hadean environment in which life could have emerged. Many locations, ranging from hydrothermal vents and pumice rafts, through volcanic-hosted splash pools to continental springs and rivers, have been proposed for the emergence of life on Earth, each with respective advantages and certain disadvantages. However, there is another, hitherto unrecognized environment that, on the Hadean Earth (4.5-4.0 Ga), would have been more important than any other in terms of spatial and temporal scale: the sedimentary layer between oceanic crust and seawater. Using as an example sediments from the 3.5-3.33 Ga Barberton Greenstone Belt, South Africa, analogous at least on a local scale to those of the Hadean eon, we document constant permeation of the porous, carbonaceous, and reactive sedimentary layer by hydrothermal fluids emanating from the crust. This partially UV-protected, subaqueous sedimentary environment, characterized by physical and chemical gradients, represented a widespread system of miniature chemical reactors in which the production and complexification of prebiotic molecules could have led to the origin of life. Key Words: Origin of life-Hadean environment-Mineral surface reactions-Hydrothermal fluids-Archean volcanic sediments. Astrobiology 18, 259-293.

Veterans with post-traumatic stress disorder exhibit altered emotional processing and attentional control during an emotional Stroop task.

BACKGROUND: Post-traumatic stress disorder (PTSD) is often associated with attention allocation and emotional regulation difficulties, but the brain dynamics underlying these deficits are unknown. The emotional Stroop task (EST) is an ideal means to monitor these difficulties, because participants are asked to attend to non-emotional aspects of the stimuli. In this study, we used magnetoencephalography (MEG) and the EST to monitor attention allocation and emotional regulation during the processing of emotionally charged stimuli in combat veterans with and without PTSD. METHOD: A total of 31 veterans with PTSD and 20 without PTSD performed the EST during MEG. Three categories of stimuli were used, including combat-related, generally threatening and neutral words. MEG data were imaged in the time-frequency domain and the network dynamics were probed for differences in processing threatening and non-threatening words. RESULTS: Behaviorally, veterans with PTSD were significantly slower in responding to combat-related relative to neutral and generally threatening words. Veterans without PTSD exhibited no significant differences in responding to the three different word types. Neurophysiologically, we found a significant three-way interaction between group, word type and time period across multiple brain regions. Follow-up testing indicated stronger theta-frequency (4-8 Hz) responses in the right ventral prefrontal (0.4-0.8 s) and superior temporal cortices (0.6-0.8 s) of veterans without PTSD compared with those with PTSD during the processing of combat-related words. CONCLUSIONS: Our data indicated that veterans with PTSD exhibited deficits in attention allocation and emotional regulation when processing trauma cues, while those without PTSD were able to regulate emotion by directing attention away from threat.

[Unexpected hemorrhage complications in association with celecoxib. Spontaneously reported case series after perioperative pain treatment in gynecological operations]. / Unerwartete Blutungskomplikationen im Zusammenhang mit Celecoxib. Spontanmeldung einer Fallserie nach perioperativer Schmerzbehandlung bei gynäkologischen Operationen.

A series of cases of postoperative bleeding were reported to the Drug Commission of the German Medical Association (Arzneimittelkommission der deutschen Ärzteschaft, AkdÄ) within the spontaneous reporting system after the regimen for postoperative pain treatment was changed from diclofenac (150 mg per day) to celecoxib (400 mg per day). All patients underwent elective gynecological surgery and 7 out of 11 patients with postoperative bleeding required revision surgery. Although alternative causes for the hemorrhage incidents could not be excluded, the documented circumstances could have been indicative of a possible causal association. Studies on perioperative pain treatment with celecoxib had previously shown no increased risk of hemorrhage. The tendency to hemorrhage observed in the registered cases could not be pharmacologically explained; however, due to the high dosages of celecoxib and the extensive co-medications used, a relative overdosing due to drug interactions or differences in the metabolism of the affected patients was conceivable. Celecoxib is not approved for the treatment of acute postoperative pain although a number of studies were carried out on the effectiveness and safety in patients undergoing surgery.

Lipid and phase specificity of α-toxin from S. aureus.

The pore forming toxin Hla (α-toxin) from Staphylococcus aureus is an important pathogenic factor of the bacterium S. aureus and also a model system for the process of membrane-induced protein oligomerisation and pore formation. It has been shown that binding to lipid membranes at neutral or basic pH requires the presence of a phosphocholine-headgroup. Thus, sphingomyelin and phosphatidylcholine may serve as interaction partners in cellular membranes. Based on earlier studies it has been suggested that rafts of sphingomyelin are particularly efficient in toxin binding. In this study we compared the oligomerisation of Hla on liposomes of various lipid compositions in order to identify the preferred interaction partners and conditions. Hla seems to have an intrinsic preference for sphingomyelin compared to phosphatidylcholine due to a higher probability of oligomerisation of membrane bound monomer. We also can show that increasing the surface density of Hla-binding sites enhances the oligomerisation efficiency. Thus, preferential binding to lipid rafts can be expected in the cellular context. On the other hand, sphingomyelin in the liquid disordered phase is a more favourable binding partner for Hla than sphingomyelin in the liquid ordered phase, which makes the membrane outside of lipid rafts the more preferred region of interaction. Thus, the partitioning of Hla is expected to strongly depend on the exact composition of raft and non-raft domains in the membrane.

Modulation of tight junction proteins in the perineurium for regional pain control.

Peripheral neurons are surrounded by the perineurium that forms the blood-nerve barrier and protects the nerve. Although the barrier serves as protection, it also hampers drug delivery of analgesic drugs to the peripheral nerve. We previously showed that opening of the barrier using hypertonic solutions facilitates drug delivery, for example, of hydrophilic opioids, which selectively target nociceptors. The perineurial barrier is formed by tight junction proteins, including claudin-1, claudin-5, and occludin. Under pathophysiological conditions such as nerve crush injury, the perineurial barrier is opened and tight junction proteins are no longer present. After several days, tight junction proteins reappear and the barrier reseals. Similarly, perineurial injection of hypertonic saline transiently opens the barrier, claudin-1 disappears, and hydrophilic analgesic drugs are effective. In the future, these findings could be used to reseal the barrier breakdown and could be applied to other barriers like the blood-brain or the intestinal mucosal barrier.

The PROCESS experiment: exposure of amino acids in the EXPOSE-E experiment on the international space station and in laboratory simulations.

To understand the chemical behavior of organic molecules in the space environment, amino acids and a dipeptide in pure form and embedded in meteorite powder were exposed in the PROCESS experiment in the EXPOSE-E facility mounted on the European Technology Exposure Facility (EuTEF) platform on board the International Space Station (ISS). After exposure to space conditions for 18 months, the samples were returned to Earth and analyzed in the laboratory for reactions caused by solar UV and cosmic radiation. Chemical degradation and possible racemization and oligomerization, the main reactions caused by photochemistry in the vacuum ultraviolet domain (VUV, wavelength range 100-200 nm for photon energy from 6.2 to 12.4 eV) were examined in particular. The molecules were extracted and derivatized by silylation and analyzed by gas chromatograph coupled to a mass spectrometer (GC-MS) to quantify the rate of the degradation of the compounds. Laboratory exposure in several wavelength ranges from UV to VUV was carried out in parallel in the Cologne Deutsches Zentrum für Luft- und Raumfahrt (DLR) Center and Centre de biophysique moléculaire (CBM) laboratories. The results show that resistance to irradiation is a function of the chemical nature of the exposed molecules and the wavelengths of the UV light. The most altered compounds were the dipeptide, aspartic acid, and aminobutyric acid. The most resistant were alanine, valine, glycine, and aminoisobutyric acid. Our results also demonstrate the protective effect of meteorite powder, which reemphasizes the importance of exogenic contribution to the inventory of prebiotic organics on early Earth.

[Extracorporeal membrane oxygenation and severe traumatic brain injury. Is the ECMO-therapy in traumatic lung failure and severe traumatic brain injury really contraindicated?]. / Extrakorporale Membranoxygenierung und schweres Schädel-Hirn-Trauma : Ist der ECMO-Einsatz bei polytraumatisierten ARDS-Patienten mit schwerem SHT wirklich noch kontraindiziert?

Veno-venous extracorporeal membrane oxygenation (ECMO) may be lifesaving in multiple injured patients with acute respiratory distress syndrome (ARDS) due to chest trauma. To prevent circuit thrombosis or thromboembolic complications during ECMO systemic anticoagulation is recommended. Therefore, ECMO treatment is contraindicated in patients with intracranial bleeding. The management of veno-venous ECMO without systemic anticoagulation in a patient suffering from traumatic lung failure and severe traumatic brain injury is reported.

Recruitment of opioid peptide-containing neutrophils is independent of formyl peptide receptors.

In complete Freund's adjuvants (CFA) inflammation opioid containing neutrophils release opioid peptides upon stimulation and mediate peripheral analgesia. Neutrophil migration is regulated partially by chemokines, but other mediators e.g. formyl peptides could also contribute. In vitro, formyl peptides but not Mycobacterium butyricum (CFA component) induced migration of neutrophils. In contrast, local formyl peptide injection did not induce leukocyte recruitment in vivo due to insufficient up-regulation of adhesion molecule expression. Furthermore, leukocyte recruitment and peripheral opioid-mediated analgesia were unaffected by systemic formyl peptide receptor blockade in CFA inflammation. Thus, while formyl peptides do not regulate migration they directly stimulate opioid peptide release.

Origin and evolution of life on terrestrial planets.

The ultimate goal of terrestrial planet-finding missions is not only to discover terrestrial exoplanets inside the habitable zone (HZ) of their host stars but also to address the major question as to whether life may have evolved on a habitable Earth-like exoplanet outside our Solar System. We note that the chemical evolution that finally led to the origin of life on Earth must be studied if we hope to understand the principles of how life might evolve on other terrestrial planets in the Universe. This is not just an anthropocentric point of view: the basic ingredients of terrestrial life, that is, reduced carbon-based molecules and liquid H(2)O, have very specific properties. We discuss the origin of life from the chemical evolution of its precursors to the earliest life-forms and the biological implications of the stellar radiation and energetic particle environments. Likewise, the study of the biological evolution that has generated the various life-forms on Earth provides clues toward the understanding of the interconnectedness of life with its environment.

[What can we learn from the Scott Reuben case? Scientific misconduct in anaesthesiology]. / Was lernen wir aus dem Fall Scott Reuben? Wissenschaftliches Fehlverhalten in der Anästhesiologie.

In February 2009 a major case of scientific misconduct was discovered. The American pain researcher Dr. S. Reuben had published 21 papers over a period of 15 years that were found to be fraudulent. Suddenly many advances in postoperative pain therapy which had been assumed to be correct seemed questionable. In this review article the lessons which can be learnt from this case are described. This review also reveals that it is almost impossible for reviewers or readers of scientific journals to detect scientific fraud. However, several warning signs can be identified that might be useful when reading clinical papers. In retrospect many of these signs were detectable in Reuben's studies. Based on the fraudulent papers of Reuben it will be shown how and to what extent falsified results can affect other types of literature, such as practice guidelines, meta-analyses, review articles and oral presentations.

Darwin--a mission to detect and search for life on extrasolar planets.

The discovery of extrasolar planets is one of the greatest achievements of modern astronomy. The detection of planets that vary widely in mass demonstrates that extrasolar planets of low mass exist. In this paper, we describe a mission, called Darwin, whose primary goal is the search for, and characterization of, terrestrial extrasolar planets and the search for life. Accomplishing the mission objectives will require collaborative science across disciplines, including astrophysics, planetary sciences, chemistry, and microbiology. Darwin is designed to detect rocky planets similar to Earth and perform spectroscopic analysis at mid-infrared wavelengths (6-20 mum), where an advantageous contrast ratio between star and planet occurs. The baseline mission is projected to last 5 years and consists of approximately 200 individual target stars. Among these, 25-50 planetary systems can be studied spectroscopically, which will include the search for gases such as CO(2), H(2)O, CH(4), and O(3). Many of the key technologies required for the construction of Darwin have already been demonstrated, and the remainder are estimated to be mature in the near future. Darwin is a mission that will ignite intense interest in both the research community and the wider public.

Antinociception by neutrophil-derived opioid peptides in noninflamed tissue--role of hypertonicity and the perineurium.

Inflammatory pain can be controlled by intraplantar opioid injection or by secretion of endogenous opioid peptides from leukocytes in inflamed rat paws. Antinociception requires binding of opioid peptides to opioid receptors on peripheral sensory nerve terminals. In the absence of inflammation, hydrophilic opioid peptides do not penetrate the perineurial barrier and, thus, do not elicit antinociception. This study was designed to examine the conditions under which endogenous, neutrophil-derived hydrophilic opioid peptides (i.e. Met-Enkephalin and beta-endorphin) can raise nociceptive thresholds in noninflamed tissue in rats. Intraplantar injection of the chemokine CXCL2/3 (macrophage inflammatory protein-2) induced selective neutrophil recruitment without overt signs of inflammation or changes in mechanical nociceptive thresholds (paw pressure threshold). Following intraplantar injection of hypertonic saline, the perineurial barrier was permeable for hours and intraplantar injection of opioid peptides increased mechanical nociceptive thresholds. While formyl-Met-Leu-Phe (fMLP) triggered opioid peptide release from neutrophils in vitro, nociceptive thresholds were unchanged in vivo. In vitro, hypertonicity interfered with fMLP-induced p38 mitogen activated kinase (MAPK) phosphorylation and opioid peptide release from neutrophils. These inhibitory effects were fully reversible by washout. In vivo, return to normotonicity occurred within 30min while the perineurium remained permeable for hours. Under these conditions, fMLP triggered MAPK phosphorylation and induced opioid peptide-mediated increases in nociceptive thresholds in the noninflamed paw. Taken together, antinociception mediated by endogenous opioids in noninflamed tissue has two important requirements: (i) opening of the perineurial barrier for opioid peptide access and (ii) opioid peptide release from neutrophils involving p38 MAPK.

[Opioid-induced immunosuppression. A clinically relevant problem?]. / Opioidinduzierte Immunsuppression. Ein klinisch relevantes Problem?

Several in vitro and animal studies have demonstrated the immunosuppressive effects of opioids and an increased risk of infection. The clinical relevance of these findings is unclear. In this review the relevant animal and human studies on the relationship of opioid use and risk of infection are summarized. The areas of retroviral infections (i.e. human immunodeficiency virus, HIV), sepsis and pneumonia, postoperative and chronic pain therapy are covered. In the majority of animal studies an increased risk of infection was demonstrated but in human studies these findings were contradictory. However, these studies were frequently underpowered because they involved small patient collectives and do not reflect the standards of evidence-based medicine. In summary, a causal relationship between opioid therapy and an increased risk of infection could neither be conclusively demonstrated nor fully excluded.

The other side of the medal: how chemokines promote analgesia.

Chemokines are chemotactic mediators controlling cell trafficking under physiological and pathological conditions. Chemokines are not only important under various inflammatory conditions but also play a role in pain and analgesia. While many studies examined the hyperalgesic action of chemokines, recent evidence also points towards antinociceptive effects of chemokines. Such effects are indirect by recruitment of opioid containing leukocytes and stimulation of release of opioid peptides. Opioid peptides then bind to opioid receptors on peripheral sensory neurons eliciting potent analgesia. This review focuses on the analgesic role of chemokines in the periphery under inflammatory and non-inflammatory conditions.

Pain and the immune system.

In inflammation, leucocytes containing opioid peptides migrate into the tissue. Opioid peptides can be released and bind to opioid receptors on peripheral nerve terminals, which counteracts inflammatory pain. Migration of opioid peptide-containing leucocytes is controlled by chemokines and adhesion molecules. Neurokinins, such as, substance P also contribute to the recruitment of these cells. Opioid peptide release from granulocytes can be stimulated by chemokines, such as, CXCR2 ligands. The release is dependent on intracellular calcium and activation of phosphoinositol-3 kinase and p38 mitogen activated kinase. Endogenous opioid peptides produced by leucocytes not only confer analgesia but recent evidence supports the concept that they also prevent the development of tolerance at peripheral opioid receptors. This review presents the discoveries that led to the concept of analgesia produced by immune-derived opioids.

Interleukin-1 beta contributes to the upregulation of kappa opioid receptor mrna in dorsal root ganglia in response to peripheral inflammation.

During local painful inflammation, axonal transport of opioid receptors from dorsal root ganglia toward the periphery is increased, associated with a higher receptor density and enhanced efficacy of opioid analgesics at the injured site. To examine whether this increase is related to transcription, mRNA of the kappa opioid receptor in lumbar dorsal root ganglia was quantified by real time light cycler polymerase chain reaction. In dorsal root ganglia of naive rats, kappa opioid receptor mRNA expression was three-fold higher than previously shown for delta opioid receptor and two times lower than mu opioid receptor mRNA, respectively. After induction of unilateral paw inflammation by Freund's complete adjuvant, kappa opioid receptor mRNA was significantly upregulated with a peak at 12 h in ipsilateral dorsal root ganglia. This effect could be mimicked by intraplantar injection of the proinflammatory cytokine interleukin-1 beta. Kappa opioid receptor mRNA upregulation lasted longer in interleukin-1 beta-treated rats compared with Freund's complete adjuvant-treated rats. Furthermore, a significant increase in kappa opioid receptor positive neurons was detected by immunohistochemistry 24 h after local injection of Freund's complete adjuvant or interleukin-1 beta. In Freund's complete adjuvant-induced inflammation, kappa opioid receptor upregulation was blocked by treatment with interleukin-1 receptor antagonist without changing the leukocyte infiltration in the paw. In conclusion, kappa opioid receptor mRNA and protein in dorsal root ganglia are upregulated in response to peripheral inflammation. This effect can be mimicked by a single local injection of interleukin-1 beta, and Freund's complete adjuvant-induced upregulation in kappa opioid receptor mRNA and protein can be prevented by treatment with interleukin-1 receptor antagonist. These data suggest that the peripheral production of the proinflammatory cytokine interleukin-1 beta is a specific inducer of kappa opioid receptor expression in the dorsal root ganglia.

[New aspects in postoperative pain therapy]. / Neue Entwicklungen in der postoperativen Schmerztherapie.

This review summarizes and critically appraises important and clinically relevant publications dealing with postoperative pain therapy. Several consequences can be drawn from these studies: i) women anticipate postoperative pain more realistically and it occurs more often than in man; however, pain intensity and analgesic consumption are not different; ii) placebos elicit psychological phenomena (e. g. expectation) that trigger neurobiological processes (e. g. activation of endogenous opioid system); iii) COX-2 inhibitors increase the risk for thromboembolic complications (e. g. myocardial infarction, apoplex, pulmonary embolism) and perioperative mortality in patients undergoing aortocoronary bypass surgery; iv) NSAID as supplement to postoperative PCIA with opioids reduce the risk for PONV and sedation; v) preoperative administration of gabapentin reduces preoperative anxiety and postoperative pain; vi) epidural catheters situated at the site of major spinal surgery are promising approach to provide efficient postoperative analgesia; vii) in the literature contradictory results have been reported regarding the effect of perioperative acupuncture on intra- and postoperative consumption of anesthetics or analgesics; acupuncture appears to decrease the incidence of PONV, but no reduction in the postoperative use of antiemetic agents has not been shown yet; viii) laparoscopic versus open colectomy in patients with colon carcinoma results in prolongation of surgery, reduction of postoperative pain and analgesics, earlier mobilization and a reduced hospital stay, if conventional systemic opioid-based pain therapy was used postoperatively.

Muscle hypertrophy induced by the Ski protein: cyto-architecture and ultrastructure.

AIM: Transgenic mice overexpressing the c-ski proto-oncogene driven by the MSV promoter undergo muscle hypertrophy, most notably fast fibres of the lower limb. This hypertrophy is not accompanied by a correspondingly large increase in force, and individual skinned muscle fibres exhibit a 30% reduction in force per cross-sectional area. In this respect, the MSV ski model is different from most other hypertrophy models and we here aim at describing the mechanisms for the reduced specific force. METHODS: Cyoarchitecture and ultrastructure of muscle fibres from the fast extensor digitorum longus muscle of 2-3 months old MSV ski mice was studied. In addition to electron microscopy, we used in vivo intracellular injections of myonuclear dye to investigate nuclear number. RESULTS: The number of nuclei did not increase in proportion to size, and consequently nuclear domains were increased compared with wild type. The fraction of the cytoplasm occupied by contractile material was reduced by 18%. In addition we observed poor intracellular alignment of Z-discs. Such staggering has been reported to reduce force in desmin deficient mice, but the amount and distribution of desmin in the MSV ski mice seemed normal. The mitochondria of MSV ski mice showed irregularly spaced cristae that were frequently disrupted. CONCLUSION: The reduction in specific force observed in MSV ski mice could be explained by a reduced fraction of contractile material and reduced transversal mechanical coupling. The ultrastructural abnormalities could be related to an increase in nuclear domains.

[Critical reevaluation of cyclooxygenase two inhibitors in perioperative pain therapy]. / Kritische Neubewertung von Zyklooxygenase-2-Inhibitoren in der perioperativen Schmerztherapie.

A significant increase in thromboembolic events (i.e. myocardial infarction and stroke) was demonstrated in multicenter studies after several months of treatment with cyclooxygenase 2 (cox-2) inhibitors. In February 2005, the European medical agencies (EMEA) substantially increased the number of contraindications for all cox-2 inhibitors. They are now contraindicated for patients with coronary artery disease. Furthermore, 2 out of 6 cox-2 inhibitors have been withdrawn from the market. In this review, the current state of knowledge on the use of cox-2 inhibitors in perioperative pain therapy is summarized: i) they are equally as potent as other non-opioid analgesics, ii) they decrease opioid consumption, iii) a reduction in postoperative nausea and vomiting (PONV) has not been adequately demonstrated. Regarding side-effects, it can be concluded that i) the incidence of thromboembolic events is increased in patients undergoing coronary artery bypass surgery, ii) perioperative blood loss is not affected, iii) ulcer formation is not promoted, iv) the risk for acute renal failure is probably increased to the same extent as for NSAIDs and v) severe bronchospasm can be triggered in patients with asthma and chronic obstructive pulmonary disease (COPD).

Rapid upregulation of mu opioid receptor mRNA in dorsal root ganglia in response to peripheral inflammation depends on neuronal conduction.

S.c. painful inflammation leads to an increase in axonal transport of opioid receptors from dorsal root ganglia (DRG) toward the periphery, thus causing a higher receptor density and enhanced opioid analgesia at the injured site. To examine whether this increase is related to transcription, the mRNA of Delta- (DOR) and mu-opioid receptor (MOR) in lumbar DRG was quantified by real time Light Cycler polymerase chain reaction (LC-PCR), and correlated to ligand binding in DRG and sciatic nerve. In normal DRG, DOR mRNA was seven times less abundantly expressed than MOR mRNA. After induction of unilateral paw inflammation, mRNA content for DOR remained unchanged, but a bi-phasic upregulation for MOR mRNA with an early peak at 1-2 h and a late increase at 96 h was found in ipsilateral DRG. As no changes were observed in DRG of the non-inflamed side, this effect was apparently not systemically mediated. A significant increase in binding of the MOR ligand DAMGO was detected after 24 h in DRG, and after early and late ligation in the sciatic nerve, indicating an enhanced axonal transport of MOR in response to inflammation. The early increase in MOR mRNA could be completely prevented by local anesthetic blockade of neuronal conduction in sciatic nerve. These data suggest that mRNA of the two opioid receptors DOR and MOR is differentially regulated in DRG during peripheral painful inflammation. The apparently increased axonal transport of MOR in response to this inflammation is preceded by upregulated mRNA-transcription, which is dependent on neuronal electrical activity.