Rapid metabolism fosters microbial survival in the deep, hot subseafloor biosphere.

A fourth of the global seabed sediment volume is buried at depths where temperatures exceed 80 °C, a previously proposed thermal barrier for life in the subsurface. Here, we demonstrate, utilizing an extensive suite of radiotracer experiments, the prevalence of active methanogenic and sulfate-reducing populations in deeply buried marine sediment from the Nankai Trough subduction zone, heated to extreme temperature (up to ~120 °C). The small microbial community subsisted with high potential cell-specific rates of energy metabolism, which approach the rates of active surface sediments and laboratory cultures. Our discovery is in stark contrast to the extremely low metabolic rates otherwise observed in the deep subseafloor. As cells appear to invest most of their energy to repair thermal cell damage in the hot sediment, they are forced to balance delicately between subsistence near the upper temperature limit for life and a rich supply of substrates and energy from thermally driven reactions of the sedimentary organic matter.

Stressful life events are associated with striatal dopamine receptor availability in alcohol dependence.

Stress plays a key role in modulating addictive behavior and can cause relapse following periods of abstinence. Common effects of stress and alcohol on the dopaminergic system have been suggested, although the precise mechanisms are unclear. Here, we investigated 20 detoxified alcohol-dependent patients and 19 matched healthy controls and assessed striatal D2/D3 availability using [18F]-fallypride positron emission tomography and stressful life events. We found a strong association between striatal D2/D3 availability and stress in patients, but not in healthy controls. Interestingly, we found increased D2/D3 receptor availability in patients with higher stress levels. This mirrors complex interactions between stress and alcohol intake in animal studies and emphasizes the importance to investigate stress exposure in neurobiological studies of addiction. CLINICAL TRIAL REGISTRATION: NCT01679145.

Three dimensional image-based simulation of ultrasonic wave propagation in polycrystalline metal using phase-field modeling.

When modeling ultrasonic wave propagation in metals, it is important to introduce mesoscopic crystalline structures because the anisotropy of the crystal structure and the heterogeneity of grains disturb ultrasonic waves. In this paper, a three-dimensional (3D) polycrystalline structure generated by multiphase-field modeling was introduced to ultrasonic simulation for nondestructive testing. 3D finite-element simulations of ultrasonic waves were validated and compared with visualization results obtained from laser Doppler vibrometer measurements. The simulation results and measurements showed good agreement with respect to the velocity and front shape of the pressure wave, as well as multiple scattering due to grains. This paper discussed the applicability of a transversely isotropic approach to ultrasonic wave propagation in a polycrystalline metal with columnar structures.

Activity studies of sesquiterpene oxides and sulfides from the plant Hyptis suaveolens (Lamiaceae) and its repellency on Ixodes ricinus (Acari: Ixodidae).

Hyptis suaveolens (Lamiaceae), a plant traditionally used as a mosquito repellent, has been investigated for repellent properties against nymphs of the tick Ixodes ricinus. Essential oils and volatile compounds of fresh and dried leaves, from plants originating from Laos and Guinea-Bissau, were identified by GC-MS and tested in a tick repellency bioassay. All the essential oils were strongly repellent against the ticks, even though the main volatile constituents differed in their proportions of potentially tick repellent chemicals. (+)/(-)-sabinene were present in high amounts in all preparations, and dominated the emission from dry and fresh leaves together with 1,8-cineol and α-phellandrene. 1,8-Cineol and sabinene were major compounds in the essential oils from H. suaveolens from Laos. Main compounds in H. suaveolens from Guinea-Bissau were (-)-sabinene, limonene and terpinolene. Among the sesquiterpene hydrocarbons identified, α-humulene exhibited strong tick repellency (96.8 %). Structure activity studies of oxidation or sulfidation products of germacrene D, α-humulene and ß-caryophyllene, showed increased tick repellent activity: of mint sulfide (59.4 %), humulene-6,7-oxide (94.5 %) and caryophyllene-6,7-oxide (96.9 %). The substitution of oxygen with sulfur slightly lowered the repellency. The effects of the constituents in the oils can then be regarded as a trade off between the subsequently lower volatility of the sesquiterpene derivatives compared to the monoterpenes and may thus increase their potential usefulness as tick repellents.

DTNBP1 (dysbindin) gene variants: in vivo evidence for effects on hippocampal glutamate status.

INTRODUCTION: In linkage and association studies the DTNBP1 gene has been identified as a major susceptibility gene for schizophrenia. Reduced expression of DTNBP1 was found in the hippocampus and prefrontal cortex in post mortem brains of schizophrenic patients. In vitro and animal models provide evidence that the DTNBP1 gene product dysbindin modulates the activity of the neurotransmitter glutamate in hippocampal neurons and is crucial for cell functioning and synaptogenesis. This study is the first to investigate the effects of genetic variants of DTNBP1 on the status of the glutamate system as well as neuronal integrity (N-acetylaspartate, NAA) in the hippocampus and a cortical region, the anterior cingulate cortex (ACC), in humans. METHODS: In 79 healthy subjects, the association of single nucleotide polymorphisms (SNPs) rs760665 and rs909706 with absolute concentrations of glutamate and NAA in the left hippocampus and the ACC were investigated, using proton magnetic resonance spectroscopy (MRS) at 3 Tesla and a well established quantification procedure. RESULTS: Hippocampal glutamate concentration was significantly affected by genotype of rs760665 (F=4.406, df=2,p=0.016) and rs909706 (F=3.171,df=2,p=0.048). For the concentration of NAA, a weak association with rs760665 was observed in the contrast analysis. None of the metabolites measured in the ACC showed a significant connection with either genotype. CONCLUSION: The results support a role of DTNBP1 gene variants in the glutamate neurotransmission system in the human brain at least in the hippocampus. This is compatible to growing evidence of a crucial role of glutamate in the pathobiology of schizophrenia. In addition, the weak association between DTNBP1 genotype and NAA is in line with a regulatory influence of dysbindin on synaptogenesis and neuronal survival.

The impact of blood pressure on hippocampal glutamate and mnestic function.

Hypertension is associated with an increased risk of cognitive decline, which is generally regarded as a consequence of advanced cerebral atherosclerosis. Many hypertensive patients, however, suffer from cognitive decline long before they have any signs of cerebrovascular disease. Therefore, this study examines direct effects of blood pressure on neurotransmitter status in the hippocampus, a vulnerable cerebral structure relevant for memory consolidation. Absolute glutamate concentration and N-acetylaspartate (NAA) concentration as an alternative marker of neuronal integrity were determined in the hippocampus and the cerebral cortex (anterior cingulate cortex; ACC) by 3-T proton magnetic resonance spectroscopy in 16 probands without any history of cerebrovascular disease. Memory function was tested by the auditory verbal learning test (AVLT) and the rivermead behavioural memory test (RBMT). Arterial stiffness was assessed by augmentation index (AI). Mean arterial pressure showed a significant negative age-adjusted correlation to absolute glutamate concentrations in the hippocampus (R=-0.655, P=0.011), but not in the ACC. There was no significant correlation of mean arterial pressure and NAA in either hippocampus or ACC. AI did not affect hippocampal glutamate. Moreover, there was a significant negative correlation between mean arterial pressure and AVLT (r=-0.558, P=0.025) and RBMT score (r=-0.555, P=0.026). There is an inverse relation between blood pressure and the concentration of hippocampal glutamate. Glutamate is essential for long-term potentiation, the neurobiological correlate for memory formation in the hippocampus. Thus, hypertension-associated cognitive decline may not only be mediated by structural atherosclerotic wall changes, but also by functional changes in neurotransmission.

Glutamate as a spectroscopic marker of hippocampal structural plasticity is elevated in long-term euthymic bipolar patients on chronic lithium therapy and correlates inversely with diurnal cortisol.

While an excess of glucocorticoids is associated with hippocampal pathology in mood disorders, lithium exerts robust neuroprotective and neurotrophic effects. Here, 21 stably remitted bipolar I patients who had been on chronic lithium maintenance therapy, on average, for more than a decade, and 19 carefully matched healthy controls were studied using 3 T (1)H-magnetic resonance spectroscopy of left and right hippocampus. Salivary cortisol samples were obtained to assess activity of the hypothalamus-pituitary-adrenal system. Absolute concentrations of N-acetylaspartate (NAA), choline-containing compounds and total creatine were similar in euthymic bipolar patients and healthy controls. Hippocampal glutamate concentrations were significantly increased as an effect of patient status (patients>controls) and laterality (left hippocampus>right hippocampus). Hippocampal glutamate content (Glu) was strongly correlated with NAA. Across groups and within the patient group, diurnal saliva cortisol levels showed a significant inverse relationship with both Glu and NAA. Taken together, these results add to the concept of bipolar disorder as an illness involving disturbed hippocampal structural plasticity under the opposing influences of lithium and glucocorticoids.

Regional cerebral glutamate concentrations and chronic tobacco consumption.

INTRODUCTION: Increasing evidence indicates a crucial role of glutamate in the brain reward system and nicotine addiction. Because the pertinent models involve frontal and hippocampal glutamatergic projections, our goal was to investigate cerebral glutamate concentrations in healthy subjects with different smoking behavior. METHODS: Glutamate was measured with proton magnetic resonance spectroscopy at 3 tesla in the left hippocampus and anterior cingulate cortex (ACC) in 13 chronic tobacco smokers, 9 former smokers, and 16 never-smokers using a dedicated quantification method. RESULTS: Glutamate concentrations did not differ between groups in either voxel ( F=1.151, DF=2, P=0.340). No significant correlations between glutamate concentrations and age of smoking onset, daily cigarette consumption, or lifetime exposure to tobacco smoke (pack-years) were observed. CONCLUSION: Our findings do not support a crucial role of cingulate or hippocampal glutamate concentration in chronic tobacco consumption. Besides group differences potentially gone unnoticed due to the limited sample size, however, these results cannot rule out dysfunctional glutamatergic neurotransmission or glutamate dysfunctions in other brain regions of smokers.

Association between cerebral glutamate and human behaviour: the sensation seeking personality trait.

INTRODUCTION: Brain imaging studies have linked the anterior cingulate cortex (ACC) to motivation, drive, and personality traits like novelty and sensation seeking. Animal studies have shown glutamatergic neurotransmission to be important in ACC function as well as motivated behaviour. However, the role of glutamate in related personality traits like sensation seeking has not been investigated in humans. METHODS: The associations between sensation seeking personality scores and absolute glutamate concentrations in the ACC and the hippocampal region measured by 3-Tesla proton magnetic resonance spectroscopy (1H-MRS) were investigated. RESULTS: ACC glutamate concentration was negatively correlated with the sensation seeking sum score and the experience seeking subscore. A weak negative correlation was also observed between the hippocampal glutamate and the sensation seeking sum score. The reexamination of the glutamate concentration after 4 weeks revealed a similar relationship with sensation seeking. DISCUSSION: Although preliminary, the results are in line with the key role of the ACC for motivation and executive control and with the impact of glutamate on novelty related behaviour observed in animal experiments. The role of the hippocampus for novelty processing is discussed. Glutamate measurement with 1H-MRS may facilitate the understanding of biological underpinnings of personality traits and psychiatric diseases associated with dysfunctions in motivation and drive.

Scaling behavior of the reorientation kinetics of block copolymers exposed to electric fields.

We have followed the reorientation kinetics of various block copolymer solutions exposed to an external electric DC field. The characteristic time constants follow a power law indicating that the reorientation is driven by a decrease in electrostatic energy. Moreover, the observed exponent suggests an activated process in line with the expectations for a nucleation and growth process. When properly scaled, the data collapse onto a single master curve spanning several orders of magnitude both in reduced time and in reduced energy. The power law dependence of the rate of reorientation derived from computer simulations based on dynamic density functional theory agrees well with the experimental observations. First experiments in AC electric fields at sufficiently high frequencies confirm the notion that the reorientation process is dominated by differences in the dielectric constants rather than by mobile ions.

Hippocampal glutamate concentration predicts cerebral theta oscillations during cognitive processing.

RATIONALE: Brain waves reflect collective behavior of neurons and provide insight into distributed network processing. Frontal and hippocampal theta oscillations (4-7 Hz) were linked to cognitive tasks and animal studies have suggested an involvement of glutamatergic neurotransmission in integrative frontal-hippocampal processing. Human evidence for such relationships is lacking. METHODS: Here, we studied the associations between glutamate concentrations in the hippocampal region, measured by a 3-T proton magnetic resonance spectroscopy (1H-MRS), and EEG theta activity during an auditory target detection paradigm. RESULTS: A robust relationship between hippocampal glutamate and frontal theta activity during stimulus processing was found. Moreover, frontal theta oscillations were related to response speed. CONCLUSION: The results suggest a functional coupling between the frontal cortex and hippocampal region during stimulus processing and support the idea of the hippocampus as a neural rhythm generator driven by glutamatergic neurotransmission. These preliminary data show, for the first time, a relationship between in vivo measured glutamate and basic cerebral information processing in humans.

Laparoscopically assisted peritoneal shunt insertion in hydrocephalus: a prospective controlled study.

BACKGROUND: Shunting of cerebrospinal fluid to the peritoneal cavity is standard therapy for the management of hydrocephalus. Common problems, however, are infection and shunt malfunction, which frequently is related to the peritoneal end of the catheter. Laparoscopic revision of distal shunt malfunction has become popular, but endoscopic techniques for primary placement of the peritoneal catheter are not performed often. This study aimed to compare laparoscopically assisted peritoneal catheter placement with the conventional minilaparotomy technique. METHODS: In the prospective arm of the study, 50 patients underwent laparoscopic distal shunt placement. The findings were compared with those for another group of 50 patients who underwent surgery by the standard transrectal or pararectal approach. Both groups were similar with regard to age, gender, American Society of Anesthesiologists (ASA) scores, indications for surgery, and frequency of previous abdominal operations. RESULTS: No intraoperative complications occurred. The mean time for surgery was 59 min in the laparoscopically assisted treatment group and 49 min in the standard group. During follow-up assessment, 3 instances of distal catheter malfunction or infection (2 malfunctions and 1 infection) occurred in the endoscopic group, and 12 instances (6 malfunctions and 6 infections) occurred in the control group. This difference was statistically significant. CONCLUSIONS: The findings from this prospective controlled study indicate that the risk for long-term complications attributable to distal shunt malfunction is reduced when laparoscopic techniques are used to place the peritoneal end of the shunt catheter.

Resonant bar simulations in media with localized damage.

As a rule, problems of wave propagation in finite media with non-uniform spatial distribution of material properties can only be tackled by numerical models. In addition, the modeling of damage features in a material requires the introduction of locally non-linear and--more important--non-unique equations of state. Using a multiscale approach, we have implemented a non-linear hysteretic stress-strain relation based on the Preisach-Mayergoyz (PM) model, into a numerical elastodynamic finite integration technique program, which has originally been developed for linearly elastic wave propagation in inhomogeneous media. The simulation results show qualitatively good agreement with data of non-linear resonant bar experiments in homogeneously non-linear and hysteretic media. When the PM density distribution of hysteretic units at the mesoscopic level is not uniform and/or confined to a finite area in stress-stress space, the response at high amplitude excitation tend to deviate from the quasi-analytical results obtained in the case of a uniform PM-space density. Localized microdamage features in an intact medium can be modeled by conceiving finite zones with pronounced hysteretic stress-strain relations within a "linear" surrounding. Forward calculations reveal a significant influence of the amplitude dependent resonance behavior on the location (edge versus center of a bar), the extend (width of the zone) and the degree (density of hysteretic units) of damage.

Informatics united: exemplary studies combining medical informatics, neuroinformatics and bioinformatics.

OBJECTIVES: Medical informatics, neuroinformatics and bioinformatics provide a wide spectrum of research. Here, we show the great potential of synergies between these research areas on the basis of four exemplary studies where techniques are transferred from one of the disciplines to the other. METHODS: Reviewing and analyzing exemplary and specific projects at the intersection of medical informatics, neuroinformatics, and bioinformatics from our experience in an interdisciplinary research group. RESULTS: Synergy emerges when techniques and solutions from medical informatics, bioinformatics, or neuroinformatics are successfully applied in one of the other disciplines. Synergy was found in 1. the modeling of neurophysiological systems for medical therapy development, 2. the use of image processing techniques from medical computer vision for the analysis of the dynamics of cell nuclei, and 3. the application of neuroinformatics tools for data mining in bioinformatics and as classifiers in clinical oncology. CONCLUSIONS: Each of the three different disciplines have delivered technologies that are readily applicable in the other disciplines. The mutual transfer of knowledge and techniques proved to increase efficiency and accuracy in a manifold of applications. In particular, we expect that clinical decision support systems based on techniques derived from neuro- and bioinformatics have the potential to improve medical diagnostics and will finally lead to a personalized delivery of healthcare.

Optical detection of elastodynamic fields of ultrasonic transducers.

By applying diffraction grids to the detection surface the full vector content of the elastic wave field of ultrasonic transducers can be measured using common heterodyne interferometers. The signal to noise ratio is good enough to detect even small edge wave contributions to the elastic wave field. Numerical simulation of the elastic wave propagation by the elastodynamic finite integration technique helps to understand the origin of several field components observed in the measurements.

Regionalisation of anterior neuroectoderm and its competence in responding to forebrain and midbrain inducing activities depend on mutual antagonism between OTX2 and GBX2.

The anterior neural ridge (ANR), and the isthmic organiser (IsO) represent two signalling centres possessing organising properties necessary for forebrain (ANR) as well as midbrain and rostral hindbrain (IsO) development. An important mediator of ANR and IsO organising property is the signalling molecule FGF8. Previous work has indicated that correct positioning of the IsO and Fgf8 expression in this domain is controlled by the transcription factors Otx2 and Gbx2. In order to provide novel insights into the roles of Otx2 and Gbx2, we have studied mutant embryos carrying different dosages of Otx2, Otx1 and Gbx2. Embryos deficient for both OTX2 and GBX2 proteins (hOtx1(2)/hOtx1(2); Gbx2(-/-)) show abnormal patterning of the anterior neural tissue, which is evident at the presomite-early somite stage prior to the onset of Fgf8 neuroectodermal expression. Indeed, hOtx1(2)/hOtx1(2); Gbx2(-/-) embryos exhibit broad co-expression of early forebrain, midbrain and rostral hindbrain markers such as hOtx1, Gbx2, Pax2, En1 and Wnt1 and subsequently fail to activate forebrain and midbrain-specific gene expression. In this genetic context, Fgf8 is expressed throughout the entire anterior neural plate, thus indicating that its activation is independent of both OTX2 and GBX2 function. Analysis of hOtx1(2)/hOtx1(2); Gbx2(-/-) and Otx1(+/-); Otx2(+/-) mutant embryos also suggests that FGF8 cannot repress Otx2 without the participation of GBX2. Finally, we report that embryos carrying a single strong hypomorphic Otx2 allele (Otx2(lambda)) in an Otx2 and Gbx2 null background (Otx2(lambda)/-; Gbx2(-/-)) recover both the headless phenotype exhibited by Otx2(lambda)/- embryos and forebrain- and midbrain-specific gene expression that is not observed in hOtx1(2)/hOtx1(2); Gbx2(-/-) mutants. Together, these data provide novel genetic evidence indicating that OTX2 and GBX2 are required for proper segregation of early regional identities anterior and posterior to the mid-hindbrain boundary (MHB) and for conferring competence to the anterior neuroectoderm in responding to forebrain-, midbrain- and rostral hindbrain-inducing activities.

Early mesodermal phenotypes in splotch suggest a role for Pax3 in the formation of epithelial somites.

The paired box containing transcription factor Pax3 is a crucial regulator of dermomyotome and muscle development. However, the allelic series of Pax3/Splotch mutants also displays characteristic vertebral column malformations, which do not result from defective dorsoventral somite pattern. Rather, vertebral column and sclerotomal phenotypes are reminiscent of the phenotypes observed in the segmentation/somitogenesis mutants rachiterata and pudgy. Moreover, rostrocaudal somite pattern and somitic boundaries are disturbed in Splotch as monitored by the expression of Uncx4.1 and Lunatic fringe. Alterations in EphA4, Dll1, and Uncx4.1 expression are evident already in the condensing paraxial mesoderm, correlating with the first phase of Pax3 expression before and during somite formation. This finding suggests an early function of Pax3 during the formation of epithelial somites.

[Anastomotic protection with a transanal tube after rectum resection and total mesorectal excision]. / Anastomosenprotektion durch transanale Drainage? Klinische Erfahrung bei 50 Patienten nach Rektumresektionen mit totaler mesorektaler Exzision und tiefen Anastomosen.

Between October 1998 and December 1999 50 patients with a primary cancer of the rectum were treated by sphincter saving anterior resection of the rectum and total mesorectal excision. Eight patients were given a neoadjuvant combined radio-chemotherapy. The anastomoses were performed in the triple-stapling technique with a Premium Plus CEEA stapling device (Fa. Tyco Health Care, Tönisvorst, Germany) or with a Proximate ILS curved stapling device (Fa. Ethicon Endo Surgery, Norderstedt, Germany). The anastomoses were situated in 7 cm or in lower distance from the anal skin. In all patients with complete anastomotic tissue rings the anastomoses were protected with the transanal tube. The integrity of the anastomosis (n = 48) was checked for completeness in the 2nd and 12th postoperative week. The patients were sigmoidoscoped and the anastomoses were controlled by transanal ultrasonography. During the hospital stay 2 patients (4.2 %) with a clinically evident anastomotic leakage were detected. 3 patients (6.2 %) with an asymptomatic anastomotic leakage were detected by computertomography. The anastomoses of 27 patients (56.2 %) were clinically and by ultrasonographical examination intact. In these patients a postoperative radiogram was not indicated. Relaparotomy was necessary in one patient for bleeding, in two patients for anastomotic leaks and in three patients for ileus (12.5 %). Because of low anastomotic leakage rate and low morbidity we find the transanal tube to be at least equivalent to conventional colostoma for anastomotic protection.