Targeted Delivery of Butyrate Improves Glucose Homeostasis, Reduces Hepatic Lipid Accumulation and Inflammation in db/db Mice.

Butyrate produced by the gut microbiota has beneficial effects on metabolism and inflammation. Butyrate-producing bacteria are supported by diets with a high fiber content, such as high-amylose maize starch (HAMS). We investigated the effects of HAMS- and butyrylated HAMS (HAMSB)-supplemented diets on glucose metabolism and inflammation in diabetic db/db mice. Mice fed HAMSB had 8-fold higher fecal butyrate concentration compared to control diet-fed mice. Weekly analysis of fasting blood glucose showed a significant reduction in HAMSB-fed mice when the area under the curve for all five weeks was analyzed. Following treatment, fasting glucose and insulin analysis showed increased homeostatic model assessment (HOMA) insulin sensitivity in the HAMSB-fed mice. Glucose-stimulated insulin release from isolated islets did not differ between the groups, while insulin content was increased by 36% in islets of the HAMSB-fed mice. Expression of insulin 2 was also significantly increased in islets of the HAMSB-fed mice, while no difference in expression of insulin 1, pancreatic and duodenal homeobox 1, MAF bZIP transcription factor A and urocortin 3 between the groups was observed. Hepatic triglycerides in the livers of the HAMSB-fed mice were significantly reduced. Finally, mRNA markers of inflammation in liver and adipose tissue were reduced in mice fed HAMSB. These findings suggest that HAMSB-supplemented diet improves glucose metabolism in the db/db mice, and reduces inflammation in insulin-sensitive tissues.

Evaluation of functional outcome measures after fampridine treatment in patients with multiple sclerosis - An interventional follow-up study.

OBJECTIVE: The purpose of this interventional study on participants with multiple sclerosis (MS) with walking disability was to evaluate changes in functional hand and walking measurements after fampridine treatment, after stratifying by the Expanded Disability Status Scale (EDSS). We furthermore wanted to investigate different functional measurements to evaluate their ability to detect responders to fampridine with a clinically relevant improvement. METHODS: Patients were recruited from the MS Clinic at Odense University Hospital and were classified into two disability groups based on their EDSS score (moderate EDSS (EDSSMod) 4.5-5.5 [n = 19] and severe EDSS (EDSSSev) 6.0-7.0 [n = 14]). At baseline (visit 1) they completed the Timed 25-Foot Walk (T25FW), 2-Minute Walk Test (2MWT), Nine Hold Peg Test (9HPT), 12-item Multiple Sclerosis Walking Scale (MSWS-12), and the Six Spot Step Test (SSST). Participants were given 10 mg twice daily fampridine for 14 days before retested (visit 2). For each measurement, cut-off values were used to define responders with a clinically relevant improvement to treatment. The measurements were evaluated separately and in combination. RESULTS: Of the 33 participants, 25 (75.8%) were identified as having a clinically relevant improvement (CRI). For all patients combined (EDSSAll), all five measurements showed significant functional improvement after treatment. For the individual measurements, the highest participant response rates after 14 days of fampridine treatment were seen on the MSWS-12 (57.6%) and 2MWT (42.4%). The 2MWT also showed the largest performance improvement (18.5%) from visit 1 to visit 2. For patients with severe disability (EDSSSev), no significant improvement was seen after fampridine treatment on the T25FW, and most of the responders to T25FW had moderate disability (EDSSMod, 71.5%). Conversely for the SSST, most responders were EDSSSev (83.3%). No participants had a clinically relevant improvement on the 9HPT. The combination of T25FW, SSST, and MSWS-12 was less sensitive in distinguishing responders from non-responders, whereas the combination of 2MWT and MSWS-12 identified the same responders and could better distinguish fampridine responders from non-responders. CONCLUSION: EDSS level did not influence the effect of fampridine treatment on functional hand and walking measures and the responsiveness of the measurements differed only a little between moderate and severe EDSS levels. The combination of self-reported walking capacity (MSWS-12) and walking endurance (2MWT) was better than T25FW, SSST, and MSWS-12 at detecting clinically meaningful improvement after fampridine treatment, which could prove useful in the clinical monitoring of walking disabilities in MS during fampridine treatment.

Microplastics in beach sediments and cockles (Anadara antiquata) along the Tanzanian coastline.

Little is known about the prevalence of microplastics (MPs) in East Africa. In the present study, sediments were sampled at 18 sites along the Tanzanian coast that exhibit different levels of anthropogenic activity and were extracted using floatation methodology. Cockles (Anadara antiquata) were collected only from eight sites and MPs were extracted following NaOH digestion. MPs were most abundant at Mtoni Kijichi Creek (MKC, 2972 ± 238 particles kg-1 dry sediment), an industrial port in Dar es Salaam, and significantly higher than all other sites where the abundance range was 15-214 particles kg-1 dry sediment (p < 0.05, one-way ANOVA). Fragments and fibers were found at all sites. Polypropylene and polyethylene were identified polymers. MPs were found in cockles from all sampled sites with both frequencies of occurrence and MPs per individual subject to site-specific variation. This study provides a baseline of MP data in a previously uninvestigated area.

The Glutamine Transporter Slc38a1 Regulates GABAergic Neurotransmission and Synaptic Plasticity.

GABA signaling sustains fundamental brain functions, from nervous system development to the synchronization of population activity and synaptic plasticity. Despite these pivotal features, molecular determinants underscoring the rapid and cell-autonomous replenishment of the vesicular neurotransmitter GABA and its impact on synaptic plasticity remain elusive. Here, we show that genetic disruption of the glutamine transporter Slc38a1 in mice hampers GABA synthesis, modifies synaptic vesicle morphology in GABAergic presynapses and impairs critical period plasticity. We demonstrate that Slc38a1-mediated glutamine transport regulates vesicular GABA content, induces high-frequency membrane oscillations and shapes cortical processing and plasticity. Taken together, this work shows that Slc38a1 is not merely a transporter accumulating glutamine for metabolic purposes, but a key component regulating several neuronal functions.

Pantoprazole in Patients at Risk for Gastrointestinal Bleeding in the ICU.

BACKGROUND: Prophylaxis for gastrointestinal stress ulceration is frequently given to patients in the intensive care unit (ICU), but its risks and benefits are unclear. METHODS: In this European, multicenter, parallel-group, blinded trial, we randomly assigned adults who had been admitted to the ICU for an acute condition (i.e., an unplanned admission) and who were at risk for gastrointestinal bleeding to receive 40 mg of intravenous pantoprazole (a proton-pump inhibitor) or placebo daily during the ICU stay. The primary outcome was death by 90 days after randomization. RESULTS: A total of 3298 patients were enrolled; 1645 were randomly assigned to the pantoprazole group and 1653 to the placebo group. Data on the primary outcome were available for 3282 patients (99.5%). At 90 days, 510 patients (31.1%) in the pantoprazole group and 499 (30.4%) in the placebo group had died (relative risk, 1.02; 95% confidence interval [CI], 0.91 to 1.13; P=0.76). During the ICU stay, at least one clinically important event (a composite of clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection, or myocardial ischemia) had occurred in 21.9% of patients assigned to pantoprazole and 22.6% of those assigned to placebo (relative risk, 0.96; 95% CI, 0.83 to 1.11). In the pantoprazole group, 2.5% of patients had clinically important gastrointestinal bleeding, as compared with 4.2% in the placebo group. The number of patients with infections or serious adverse reactions and the percentage of days alive without life support within 90 days were similar in the two groups. CONCLUSIONS: Among adult patients in the ICU who were at risk for gastrointestinal bleeding, mortality at 90 days and the number of clinically important events were similar in those assigned to pantoprazole and those assigned to placebo. (Funded by Innovation Fund Denmark and others; SUP-ICU ClinicalTrials.gov number, NCT02467621 .).

Re-oxygenation after anoxia induces brain cell death and memory loss in the anoxia-tolerant crucian carp.

Crucian carp (Carassius carassius) survive without oxygen for several months, but it is unknown whether they are able to protect themselves from cell death normally caused by the absence, and particularly return, of oxygen. Here, we quantified cell death in brain tissue from crucian carp exposed to anoxia and re-oxygenation using the terminal deoxy-nucleotidyl transferase dUTP nick-end labelling (TUNEL) assay, and cell proliferation by immunohistochemical staining for proliferating cell nuclear antigen (PCNA) as well as PCNA mRNA expression. We also measured mRNA and protein expression of the apoptosis executer protease caspase 3, in laboratory fish exposed to anoxia and re-oxygenation and fish exposed to seasonal anoxia and re-oxygenation in their natural habitat over the year. Finally, a behavioural experiment was used to assess the ability to learn and remember how to navigate in a maze to find food, before and after exposure to anoxia and re-oxygenation. The number of TUNEL-positive cells in the telencephalon increased after 1 day of re-oxygenation following 7 days of anoxia, indicating increased cell death. However, there were no consistent changes in whole-brain expression of caspase 3 in either laboratory-exposed or naturally exposed fish, indicating that cell death might occur via caspase-independent pathways or necrosis. Re-oxygenated crucian carp appeared to have lost the memory of how to navigate in a maze (learnt prior to anoxia exposure), while the ability to learn remained intact. PCNA mRNA was elevated after re-oxygenation, indicating increased neurogenesis. We conclude that anoxia tolerance involves not only protection from damage but also repair after re-oxygenation.

Targeted Temperature Management for 48 vs 24 Hours and Neurologic Outcome After Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial.

Importance: International resuscitation guidelines recommend targeted temperature management (TTM) at 33°C to 36°C in unconscious patients with out-of-hospital cardiac arrest for at least 24 hours, but the optimal duration of TTM is uncertain. Objective: To determine whether TTM at 33°C for 48 hours results in better neurologic outcomes compared with currently recommended, standard, 24-hour TTM. Design, Setting, and Participants: This was an international, investigator-initiated, blinded-outcome-assessor, parallel, pragmatic, multicenter, randomized clinical superiority trial in 10 intensive care units (ICUs) at 10 university hospitals in 6 European countries. Three hundred fifty-five adult, unconscious patients with out-of-hospital cardiac arrest were enrolled from February 16, 2013, to June 1, 2016, with final follow-up on December 27, 2016. Interventions: Patients were randomized to TTM (33 ± 1°C) for 48 hours (n = 176) or 24 hours (n = 179), followed by gradual rewarming of 0.5°C per hour until reaching 37°C. Main Outcomes and Measures: The primary outcome was 6-month neurologic outcome, with a Cerebral Performance Categories (CPC) score of 1 or 2 used to define favorable outcome. Secondary outcomes included 6-month mortality, including time to death, the occurrence of adverse events, and intensive care unit resource use. Results: In 355 patients who were randomized (mean age, 60 years; 295 [83%] men), 351 (99%) completed the trial. Of these patients, 69% (120/175) in the 48-hour group had a favorable outcome at 6 months compared with 64% (112/176) in the 24-hour group (difference, 4.9%; 95% CI, -5% to 14.8%; relative risk [RR], 1.08; 95% CI, 0.93-1.25; P = .33). Six-month mortality was 27% (48/175) in the 48-hour group and 34% (60/177) in the 24-hour group (difference, -6.5%; 95% CI, -16.1% to 3.1%; RR, 0.81; 95% CI, 0.59-1.11; P = .19). There was no significant difference in the time to mortality between the 48-hour group and the 24-hour group (hazard ratio, 0.79; 95% CI, 0.54-1.15; P = .22). Adverse events were more common in the 48-hour group (97%) than in the 24-hour group (91%) (difference, 5.6%; 95% CI, 0.6%-10.6%; RR, 1.06; 95% CI, 1.01-1.12; P = .04). The median length of intensive care unit stay (151 vs 117 hours; P < .001), but not hospital stay (11 vs 12 days; P = .50), was longer in the 48-hour group than in the 24-hour group. Conclusions and Relevance: In unconscious survivors from out-of-hospital cardiac arrest admitted to the ICU, targeted temperature management at 33°C for 48 hours did not significantly improve 6-month neurologic outcome compared with targeted temperature management at 33°C for 24 hours. However, the study may have had limited power to detect clinically important differences, and further research may be warranted. Trial Registration: clinicaltrials.gov Identifier: NCT01689077.

On the Role of Neurogenesis and Neural Plasticity in the Evolution of Animal Personalities and Stress Coping Styles.

Individual variation in how animals react to stress and environmental change has become a central topic in a wide range of biological disciplines, from evolutionary ecology to biomedicine. Such variation manifests phenotypically as correlated trait-clusters (referred to as coping styles, behavioral syndromes, shyness-boldness, or personality traits). Thresholds for switching from active coping (fight-flight) to inhibition and passive behavior when exposed to stress depend on experience and genetic factors. Comparative research has revealed a range of neuroendocrine-behavioral associations which are conserved throughout the vertebrate subphylum, including factors affecting perception, learning, and memory of stimuli and events. Here we review conserved aspects of the contribution of neurogenesis and other aspects of neural plasticity to stress coping. In teleost fish, brain cell proliferation and neurogenesis have received recent attention. This work reveals that brain cell proliferation and neurogenesis are associated with heritable variation in stress coping style, and they are also differentially affected by short- and long-term stress in a biphasic manner. Routine-dependent and inflexible behavior in proactive individuals is associated with limited neural plasticity. These evolutionarily conserved relationships hold the potential to illuminate the biological background for stress-related neurobiological disorders.

Anion-Tunable Properties and Electrochemical Performance of Functionalized Ferrocene Compounds.

We report a series of ionically modified ferrocene compounds for hybrid lithium-organic non-aqueous redox flow batteries, based on the ferrocene/ferrocenium redox couple as the active catholyte material. Tetraalkylammonium ionic moieties were incorporated into the ferrocene structure, in order to enhance the solubility of the otherwise relatively insoluble ferrocene. The effect of various counter anions of the tetraalkylammonium ionized species appended to the ferrocene, such as bis(trifluoromethanesulfonyl)imide, hexafluorophosphate, perchlorate, tetrafluoroborate, and dicyanamide on the solubility of the ferrocene was investigated. The solution chemistry of the ferrocene species was studied, in order to understand the mechanism of solubility enhancement. Finally, the electrochemical performance of these ionized ferrocene species was evaluated and shown to have excellent cell efficiency and superior cycling stability.

ViSAPy: a Python tool for biophysics-based generation of virtual spiking activity for evaluation of spike-sorting algorithms.

BACKGROUND: New, silicon-based multielectrodes comprising hundreds or more electrode contacts offer the possibility to record spike trains from thousands of neurons simultaneously. This potential cannot be realized unless accurate, reliable automated methods for spike sorting are developed, in turn requiring benchmarking data sets with known ground-truth spike times. NEW METHOD: We here present a general simulation tool for computing benchmarking data for evaluation of spike-sorting algorithms entitled ViSAPy (Virtual Spiking Activity in Python). The tool is based on a well-established biophysical forward-modeling scheme and is implemented as a Python package built on top of the neuronal simulator NEURON and the Python tool LFPy. RESULTS: ViSAPy allows for arbitrary combinations of multicompartmental neuron models and geometries of recording multielectrodes. Three example benchmarking data sets are generated, i.e., tetrode and polytrode data mimicking in vivo cortical recordings and microelectrode array (MEA) recordings of in vitro activity in salamander retinas. The synthesized example benchmarking data mimics salient features of typical experimental recordings, for example, spike waveforms depending on interspike interval. COMPARISON WITH EXISTING METHODS: ViSAPy goes beyond existing methods as it includes biologically realistic model noise, synaptic activation by recurrent spiking networks, finite-sized electrode contacts, and allows for inhomogeneous electrical conductivities. ViSAPy is optimized to allow for generation of long time series of benchmarking data, spanning minutes of biological time, by parallel execution on multi-core computers. CONCLUSION: ViSAPy is an open-ended tool as it can be generalized to produce benchmarking data or arbitrary recording-electrode geometries and with various levels of complexity.

Enzyme design from the bottom up: an active nickel electrocatalyst with a structured peptide outer coordination sphere.

Catalytic, peptide-containing metal complexes with a well-defined peptide structure have the potential to enhance molecular catalysts through an enzyme-like outer coordination sphere. Here, we report the synthesis and characterization of an active, peptide-based metal complex built upon the well-characterized hydrogen production catalyst [Ni(P(Ph)2N(Ph))2](2+) (P(Ph)2N(Ph)=1,3,6-triphenyl-1-aza-3,6-diphosphacycloheptane). The incorporated peptide maintains its ß-hairpin structure when appended to the metal core, and the electrocatalytic activity of the peptide-based metal complex (≈100,000 s(-1)) is enhanced compared to the parent complex ([Ni(P(Ph)2N(APPA))2](2+); ≈50,500 s(-1)). The combination of an active molecular catalyst with a structured peptide provides a scaffold that permits the incorporation of features of an enzyme-like outer-coordination sphere necessary to create molecular electrocatalysts with enhanced functionality.

Abatement of xenon and iodine emissions from medical isotope production facilities.

The capability of the International Monitoring System (IMS) to detect xenon from underground nuclear explosions is dependent on the radioactive xenon background. Adding to the background, medical isotope production (MIP) by fission releases several important xenon isotopes including xenon-133 and iodine-133 that decays to xenon-133. The amount of xenon released from these facilities may be equivalent to or exceed that released from an underground nuclear explosion. Thus the release of gaseous fission products within days of irradiation makes it difficult to distinguish MIP emissions from a nuclear explosion. In addition, recent shortages in molybdenum-99 have created interest and investment opportunities to design and build new MIP facilities in the United States and throughout the world. Due to the potential increase in the number of MIP facilities, a discussion of abatement technologies provides insight into how the problem of emission control from MIP facilities can be tackled. A review of practices is provided to delineate methods useful for abatement of medical isotopes.

Coping with unpredictability: dopaminergic and neurotrophic responses to omission of expected reward in Atlantic salmon (Salmo salar L.).

Comparative studies are imperative for understanding the evolution of adaptive neurobiological processes such as neural plasticity, cognition, and emotion. Previously we have reported that prolonged omission of expected rewards (OER, or 'frustrative nonreward') causes increased aggression in Atlantic salmon (Salmo salar). Here we report changes in brain monoaminergic activity and relative abundance of brain derived neurotrophic factor (BDNF) and dopamine receptor mRNA transcripts in the same paradigm. Groups of fish were initially conditioned to associate a flashing light with feeding. Subsequently, the expected food reward was delayed for 30 minutes during two out of three meals per day in the OER treatment, while the previously established routine was maintained in control groups. After 8 days there was no effect of OER on baseline brain stem serotonin (5-HT) or dopamine (DA) activity. Subsequent exposure to acute confinement stress led to increased plasma cortisol and elevated turnover of brain stem DA and 5-HT in all animals. The DA response was potentiated and DA receptor 1 (D1) mRNA abundance was reduced in the OER-exposed fish, indicating a sensitization of the DA system. In addition OER suppressed abundance of BDNF in the telencephalon of non-stressed fish. Regardless of OER treatment, a strong positive correlation between BDNF and D1 mRNA abundance was seen in non-stressed fish. This correlation was disrupted by acute stress, and replaced by a negative correlation between BDNF abundance and plasma cortisol concentration. These observations indicate a conserved link between DA, neurotrophin regulation, and corticosteroid-signaling pathways. The results also emphasize how fish models can be important tools in the study of neural plasticity and responsiveness to environmental unpredictability.

Protein markers for identification of Yersinia pestis and their variation related to culture.

The detection of high consequence pathogens, such as Yersinia pestis, is well established in biodefense laboratories for bioterror situations. Laboratory protocols are well established using specified culture media and a growth temperature of 37 °C for expression of specific antigens. Direct detection of Y. pestis protein markers, without prior culture, depends on their expression. Unfortunately protein expression can be impacted by the culture medium which cannot be predicted ahead of time. Furthermore, higher biomass yields are obtained at the optimal growth temperature (i.e. 28 °C-30 °C) and therefore are more likely to be used for bulk production. Analysis of Y. pestis grown on several types of media at 30 °C showed that several protein markers were found to be differentially detected in different media. Analysis of the identified proteins against a comprehensive database provided an additional level of organism identification. Peptides corresponding to variable regions of some proteins could separate large groups of strains and aid in organism identification. This work illustrates the need to understand variability of protein expression for detection targets. The potential for relating expression changes of known proteins to specific media factors, even in nutrient rich and chemically complex culture medium, may provide the opportunity to draw forensic information from protein profiles.

Aerobic vs. anaerobic scope: sibling species of fish indicate that temperature dependence of hypoxia tolerance can predict future survival.

The temperature dependence of aerobic scope has been suggested to be a major determinant of how marine animals will cope with future rises in environmental temperature. Here, we present data suggesting that in some animals, the temperature dependence of anaerobic scope (i.e., the capacity for surviving severe hypoxia) may determine present-day latitudinal distributions and potential for persistence in a warmer future. As a model for investigating the role of anaerobic scope, we studied two sibling species of coral-dwelling gobies, Gobiodon histrio, and G. erythrospilus, with different latitudinal distributions, but which overlap in equal abundance at Lizard Island (14°40'S) on the Great Barrier Reef. These species did not differ in the temperature dependence of resting oxygen consumption or critical oxygen concentration (the lowest oxygen level where resting oxygen consumption can be maintained). In contrast, the more equatorial species (G. histrio) had a better capacity to endure anaerobic conditions at oxygen levels below the critical oxygen concentration at the high temperatures (32-33 °C) more likely to occur near the equator, or in a warmer future. These results suggest that anaerobic scope, in addition to aerobic scope, could be important in determining the impacts of global warming on some marine animals.

Diagnosis and outcome in a prehospital cohort of patients with bundle branch block and suspected acute myocardial infarction.

BACKGROUND: Immediate revascularization is beneficial in patients with presumed new-onset bundle branch block myocardial infarction (BBBMI). In the prehospital setting, it is a challenge to diagnose new-onset BBBMI and triage accordingly. METHODS: ECG, final diagnosis, and mortality were assessed in a prehospital cohort of 4905 consecutive patients with suspected acute myocardial infarction (AMI). Bundle branch block (BBB) was defined as QRS duration ≥120 ms caused by delayed intraventricular conduction. Mortality and angiography data were obtained from the Central Office of Civil Registration and the Western Denmark Heart Registry. Definite diagnosis of AMI and the onset of BBB were determined by expert consensus. Patients were divided into four groups: with or without AMI and with or without BBB. Mortality was evaluated by Kaplan-Meier plots and compared using log-rank statistics. RESULTS: AMI was diagnosed in 954 patients, of whom 118 had BBB. In 3951 patients without AMI, 436 had BBB. Patients with BBBMI were less often revascularized than patients with AMI without BBB (24 vs. 54%, p<0.001). BBBMI was categorized as new onset in 43 patients of whom two were triaged for acute angioplasty. One-year mortality was 47.2, 17.5, 20.8, and 8.6% (log-rank <0.001) in patients with BBBMI, patients with AMI without BBB, patients with BBB without AMI, and patients without AMI or BBB, respectively. CONCLUSIONS: Patients with BBBMI have a high mortality. Less than 25% undergo revascularization and only very few patients with new-onset BBBMI are transferred for urgent revascularization. Focus on improving triage and prehospital identification of high-risk patients with BBB and chest pain could improve outcome.

Neural plasticity and stress coping in teleost fishes.

Physiological and behavioural responses to environmental change are individually variable traits, which manifest phenotypically and are subject to natural selection as correlated trait-clusters (coping styles, behavioural syndromes, or personality traits). Comparative research has revealed a range of neuroendocrine-behavioural associations which are conserved throughout the vertebrate subphylum. Regulatory mechanisms universally mediate a switch between proactive (e.g. active/aggressive) and reactive (e.g. conservation/withdrawal) behaviour in response to unpredictable and uncontrollable events. Thresholds for switching from active coping to behavioural inhibition are individually variable, and depend on experience and genetic factors. Such factors affect physiological stress responses as well as perception, learning, and memory. Here we review the role of an important contributor to neural processing, the set of biochemical, molecular, and structural processes collectively referred to as neural plasticity. We will concentrate on work in teleost fishes, while also elucidating conserved aspects. In fishes, environmental and physiological control of brain cell proliferation and neurogenesis has received recent attention. This work has revealed that the expression of genes involved in CNS plasticity is affected by heritable variation in stress coping style, and is also differentially affected by short- and long-term stress. Chronic stress experienced by subordinate fish in social hierarchies leads to a marked suppression of brain cell proliferation. Interestingly, typically routine dependent and inflexible behaviour in proactive individuals is also associated with low transcription of neurogenesis related genes. The potential for these findings to illuminate stress-related neurobiological disorders in other vertebrates is also discussed.

Characterization of diesel fuel by chemical separation combined with capillary gas chromatography (GC) isotope ratio mass spectrometry (IRMS).

The purpose of this study was to perform a preliminary investigation of compound-specific isotope analysis (CSIA) of diesel fuels to evaluate whether the technique could distinguish diesel samples from different sources/locations. The ability to differentiate or correlate diesel samples could be valuable for discovering fuel tax evasion schemes or for environmental forensic studies. Two urea adduction-based techniques were used to isolate the n-alkanes from the fuel. Both carbon isotope ratio (δ(13)C) and hydrogen isotope ratio (δD) values for the n-alkanes were then determined by CSIA in each sample. The samples investigated had δ(13)C values that ranged from -30.1‰ to -26.8‰, whereas δD values ranged from -83‰ to -156‰. Plots of δD versus δ(13)C with sample n-alkane points connected in order of increasing carbon number gave well-separated clusters with characteristic shapes for each sample. Principal components analysis (PCA) with δ(13)C, δD, or combined δ(13)C and δD data was applied to extract the maximum information content. PCA scores plots could clearly differentiate the samples, thereby demonstrating the potential of this approach for distinguishing (e.g., fingerprinting) fuel samples using δ(13)C and δD values.

Neural plasticity is affected by stress and heritable variation in stress coping style.

Here we use a comparative model to investigate how behavioral and physiological traits correlate with neural plasticity. Selection for divergent post-stress cortisol levels in rainbow trout (Oncorhynchus mykiss) has yielded low- (LR) and high responsive (HR) lines. Recent reports show low behavioral flexibility in LR compared to HR fish and we hypothesize that this divergence is caused by differences in neural plasticity. Genes involved in neural plasticity and neurogenesis were investigated by quantitative PCR in brains of LR and HR fish at baseline conditions and in response to two different stress paradigms: short-term confinement (STC) and long-term social (LTS) stress. Expression of proliferating cell nuclear antigen (PCNA), neurogenic differentiation factor (NeuroD) and doublecortin (DCX) was generally higher in HR compared to LR fish. STC stress led to increased expression of PCNA and brain-derived neurotrophic factor (BDNF) in both lines, whereas LTS stress generally suppressed PCNA and NeuroD expression while leaving BDNF expression unaltered. These results indicate that the transcription of neuroplasticity-related genes is associated with variation in coping style, while also being affected by STC - and LTS stress in a biphasic manner. A higher degree of neural plasticity in HR fish may provide the substrate for enhanced behavioral flexibility.