Serotonin-1A Receptor Polymorphism (rs6295) Associated with Thermal Pain Perception

Background

Serotonin (5-HT) is highly involved in pain regulation and serotonin-1A (5-HT1A) receptors are important in determining central 5-HT tone. Accordingly, variation in the 5-HT1A receptor gene (HTR1A) may contribute to inter-individual differences in human pain sensitivity. The minor G-allele of the HTR1A single nucleotide polymorphism (SNP) rs6295 attenuates firing of serotonergic neurons and reduces postsynaptic expression of the receptor. Experiments in rodents suggest that 5-HT1A-agonism modulates pain in opposite directions at mild compared to high noxious intensities. Based upon this and several other similar observations, we hypothesized that G-carriers would exhibit a relative hypoalgesia at mild thermal stimuli but tend towards hyperalgesia at higher noxious intensities.

Methods

Fourty-nine healthy individuals were selectively genotyped for rs6295. Heat- and cold-pain thresholds were assessed along with VAS-ratings of a range of suprathreshold noxious heat intensities (45°C–49°C). Nociceptive-flexion reflex (NFR) thresholds were also assessed.

Results

Volunteers did not deviate significantly from Hardy-Weinberg equilibrium. G-carriers were less sensitive to threshold-level thermal pain. This relative hypoalgesia was abolished at suprathreshold noxious intensities where G-carriers instead increased their ratings of heat-pain significantly more than C-homozygotes. No differences with regard to NFR-thresholds emerged.

Conclusion/Significance

To the best of our knowledge this is the first study of human pain perception on the basis of variation in HTR1A. The results illustrate the importance of including a range of stimulus intensities in assessments of pain sensitivity. In speculation, we propose that an attenuated serotonergic tone may be related to a ‘hypo- to hyperalgesic’ response-pattern. The involved mechanisms could be of clinical interest as variation in pain regulation is known to influence the risk of developing pain pathologies. Further investigations are therefore warranted.     

OMERO: flexible, model-driven data management for experimental biology

Data-intensive research depends on tools that manage multidimensional, heterogeneous datasets. We built OME Remote Objects (OMERO), a software platform that enables access to and use of a wide range of biological data. OMERO uses a server-based middleware application to provide a unified interface for images, matrices and tables. OMERO's design and flexibility have enabled its use for light-microscopy, high-content-screening, electron-microscopy and even non-image-genotype data. OMERO is open-source software, available at http://openmicroscopy.org/.     

Biochemical Composition of Dissolved Organic Carbon Derived from Phytoplankton and Used by Heterotrophic Bacteria

The molecular size distribution and biochemical composition of the dissolved organic carbon released from natural communities of lake phytoplankton (photosynthetically produced dissolved organic carbon [PDOC]) and subsequently used by heterotrophic bacteria were determined in three lakes differing in trophic status and concentration of humic substances. After incubation of epilimnetic lake water samples with H¹⁴CO₃^- over one diel cycle, the phytoplankton were removed by size-selective filtration. The filtrates, still containing most of the heterotrophic bacteria, were reincubated in darkness (heterotrophic incubation). Differences in the amount and composition of PDO¹⁴C between samples collected before the heterotrophic incubation and samples collected afterwards were considered to be a result of bacterial utilization. The PDO¹⁴C collected at the start of the heterotrophic incubations always contained both high (>10,000)- and low (<1,000)-molecular-weight (MW) components and sometimes contained intermediate-MW components as well. In general, bacterial turnover rates of the low-MW components were fairly rapid, whereas the high-MW components were utilized slowly or not at all. In the humic lake, the intermediate-MW components accounted for a large proportion of the net PDO¹⁴C and were subject to rapid bacterial utilization. This fraction probably consisted almost entirely of polysaccharides of ca. 6,000 MW. Amino acids and peptides, other organic acids, and carbohydrates could all be quantitatively important parts of the low-MW PDO¹⁴C that was utilized by the heterotrophic bacteria, but the relative contributions of these fractions differed widely. It was concluded that, generally, low-MW components of PDOC are quantitatively much more important to the bacteria than are high-MW components, that PDOC released from phytoplankton does not contain substances of quantitative importance as bacterial substrates in all situations, and that high-MW components of PDOC probably contribute to the buildup of refractory, high-MW dissolved organic carbon in pelagic environments.     

Effects of metabolic rate on thermal responses at different air velocities in −10°C

The effects of exercise intensity on thermoregulatory responses in cold (−10°C) in a 0.2 (still air, NoWi), 1.0 (Wi1), and 5.0 (Wi5) m s⁻¹ wind were studied. Eight young and healthy men, preconditioned in thermoneutral (+20°C) environment for 60 min, walked for 60 min on the treadmill at 2.8 km/h with different combinations of wind and exercise intensity. Exercise level was adjusted by changing the inclination of the treadmill between 0° (lower exercise intensity, metabolic rate 124 W m⁻², LE) and 6° (higher exercise intensity, metabolic rate 195 W m⁻², HE). Due to exercise increased heat production and circulatory adjustments, the rectal temperature (T_re), mean skin temperature (T_sk) and mean body temperature (T_b) were significantly higher at the end of HE in comparison to LE in NoWi and Wi1, and T_re and T_b also in Wi5. T_sk and T_b were significantly decreased by 5.0 m s⁻¹ wind in comparison to NoWi and Wi1. The higher exercise intensity was intense enough to diminish peripheral vasoconstriction and consequently the finger skin temperature was significantly higher at the end of HE in comparison to LE in NoWi and Wi1. Mean heat flux from the skin was unaffected by the exercise intensity. At LE oxygen consumption (V ₂) was significantly higher in Wi5 than NoWi and Wi1. Heart rate was unaffected by the wind speed. The results suggest that, with studied exercise intensities, produced without changes in walking speed, the metabolic rate is not so important that it should be taken into consideration in the calculation of wind chill index.     

Effects of glucose overloading on microbial community structure and biogas production in a laboratory-scale anaerobic digester

This study characterizes the response of the microbial communities of a laboratory-scale mesophilic biogas process, fed with a synthetic substrate based on cellulose and egg albumin, to single pulses of glucose overloading (15 or 25 times the daily feed based on VS). The microbial biomass and community structure were determined from analyses of membrane phospholipids. The ratio between phospholipid fatty acids (PLFAs; eubacteria and eucaryotes) and di-ethers (PLEL; archaea) suggested that methanogens constituted 4-8% of the microbial biomass. The glucose addition resulted in transient increases in the total biomass of eubacteria while there were only small changes in community structure. The total gas production rate increased, while the relative methane content of the biogas and the alkalinity decreased. However, the biomass of methanogens was not affected by the glucose addition. The results show that the microbial communities of biogas processes can respond quickly to changes in the feeding rate. The glucose overload resulted in a transient general stimulation of degradation rates and almost a doubling of eubacterial biomass, although the biomass increase corresponded to only 7% of the glucose C added.     

Predicting polygynous settlement while incorporating varying female competitive strength

The rationale behind the polygyny threshold model is that thebreeding situation quality (BSQ) males have to offer femalesvaries, and that differences in BSQ offset females' costs ofsharing with other females, thus favoring polygynous settling.It predicts that the first chosen territories become polygynousfirst, and that breeding success of secondary and contemporarymonogamous females is similar. This is not generally found.Testing of the polygyny threshold model (PTM) assumes that femalesare equal competitors and distribute ideally free around availablebreeding resources, a condition probably not often met. If sharinga male is costly, and competitors differ in quality, weakerindividuals should experience degrees of competitive exclusion.Setting female competitive abilities proportional to arrivalorder, we use an individual-based interference-competition modelto examine settlement patterns. Shifts in the ratio of variancein interfemale competitiveness to interterritorial differencesin BSQ result in various settlement patterns, with differentpredictions concerning settlement order and fitness returns.We find support for the novel predictions from data on northernlapwing (Vanellus vanellus), starling (Sturnus vulgaris), piedflycatcher (Ficedula hypoleuca), and blue tit (Parus caeruleus).We suggest that before testing polygyny predictions, an evaluationof the settlement sequence should be made, which may help togenerate more accurate predictions. We argue that violationof the "equal female" assumption may explain much of the discrepancybetween predictions and empirical findings in previous testsof the PTM, and that secondary females in general have lowersuccess than do monogamous breeders because they are of lowerquality.     

Purification,localization, and expression of human intestinal alkaline sphingomyelinase

Sphingomyelin (SM) metabolism in the gut may have an impact on colon cancer development. In this study, we purified alkaline sphingomyelinase (alk-SMase) from human intestinal content, and studied its location in the mucosa, expression in colon cancer, and function on colon cancer cells. The enzyme was purified by a series of chromatographies. The molecular mass of the enzyme is 60 kDa, optimal pH is 8.5, and isoelectric point is 6.6. Under optimal conditions, 1 mg of the enzyme hydrolyzed 11 mM SM per hour. The properties of the enzyme are similar to those of rat intestinal alk-SMase but not to those of bacterial neutral SMase. Immunogold electronmicroscopy identified the enzyme on the microvillar membrane in endosome-like structures and in the Golgi complexes of human enterocytes. The expression and the activity of the enzyme were decreased in parallel in human colon cancer tissues compared with the adjacent normal tissue. The enzyme inhibited DNA biosynthesis and cell proliferation dose dependently and caused a reduction of SM in HT29 cells. Intestinal alk-SMase is localized in the enterocytes, down-regulated in human colon cancer, and may have antiproliferative effects on colon cancer cells.     

Implementation and application of a versatile clustering tool for tandem mass spectrometry data

High-throughput proteomics experiments typically generate large amounts of peptide fragmentation mass spectra during a single experiment. There is often a substantial amount of redundant fragmentation of the same precursors among these spectra, which is usually considered a nuisance. We here discuss the potential of clustering and merging redundant spectra to turn this redundancy into a useful property of the dataset. To this end, we have created the first general-purpose, freely available open-source software application for clustering and merging MS/MS spectra. The application also introduces a novel approach to calculating the similarity of fragmentation mass spectra that takes into account the increased precision of modern mass spectrometers, and we suggest a simple but effective improvement to single-linkage clustering. The application and the novel algorithms are applied to several real-life proteomic datasets and the results are discussed. An analysis of the influence of the different algorithms available and their parameters is given, as well as a number of important applications of the overall approach.     

Sea surface temperature dictates movement and habitat connectivity of Atlantic cod in a coastal fjord system

While movements of organisms have been studied across a myriad of environments, information is often lacking regarding spatio‐seasonal patterning in complex temperate coastal systems. Highly mobile fish form an integral part of marine food webs providing linkages within and among habitats, between patches of habitats, and at different life stages. We investigated how movement, activity, and connectivity patterns of Atlantic cod (Gadus morhua) are influenced by dynamic environmental conditions. Movement patterns of 39 juvenile and subadult Atlantic cod were assessed in two coastal sites in the Swedish Skagerrak for 5 months. We used passive acoustic telemetry and network analysis to assess seasonal and spatial movement patterns of cod and their relationships to different environmental factors, using statistical correlations, analysis of recurrent spatial motifs, and generalized linear mixed models. Temperature, in combination with physical barriers, precludes significant connectivity (complex motifs) within the system. Sea surface temperature had a strong influence on connectivity (node strength, degree, and motif frequency), where changes from warmer summer waters to colder winter waters significantly reduced movement activity of fish. As the seasons changed, movement of fish gradually decreased from large‐scale (km) linkages in the summer to more localized movement patterns in the winter (limited to 100s m). Certain localized areas, however, were identified as important for connectivity throughout the whole study period, likely due to these multiple‐habitat areas fulfilling functions required for foraging and shelter. This study provides new knowledge regarding inshore movement dynamics of juvenile and subadult Atlantic cod that use complex, coastal fjord systems. The findings show that connectivity, seasonal patterns in particular, should be carefully considered when selecting conservation areas to promote marine stewardship.