Comparative studies of somatostatin-14 and some of its fragments on passive avoidance behavior, open field activity and on barrel rotation phenomenon in rats

Behavioral effects of somatostatin-14, and some of its fragments [somatostatin(3–8), somatostatin(9–14), somatostatin(7–10)] after intracerebroventricular (ICV) administration have been investigated in male rats. In a passive avoidance learning test, somatostatin-14 (0.6 nM) given immediately after the learning session increased the avoidance latency at 24 hr after the injection, when compared to a somatostatin(3–8) (0.6 nM)-treated group. However, compared to a saline-treated group, the peptides did not significantly influence the avoidance latency. Somatostatin-14 administered in higher dose (6.0 nM) decreased the avoidance latency compared to the saline-treated group, while its fragments did not influence it. In an open field behavioral test, immediately after the 24-hr passive avoidance test, 6 nM of somatostatin-14 decreased the rearing activity, while the fragments did not influence this behavior. Somatostatin-14 produced barrel rotation in a dose-related manner, but after the injection of a high dose of the peptide (12 nM) all of the animals died in cardiorespiratory failure (apnea, pulmonary oedema). The fragments did not produce barrel rotation.     

gltF, a member of the gltBDF operon of Escherichia coli, is involved in nitrogen-regulated gene expression

We report here the construction and analysis of insertional mutations in each of the three genes of the gltBDF operon and the nucleotide sequence of the region downstream from gltD. Two open reading frames were identified, the first of which corresponds to gltF. The gltB and gltD genes code for the large and small subunits, respectively, of the enzyme glutamate synthase (GOGAT). gltF codes for a protein, with a molecular mass of 26,350 Da, which is required for Ntr induction. Histidase synthesis was determined as a measure of Ntr function. First, insertions in gltB, gltD or gltF all prevent Ntr induction. Second, complementation analysis indicates that high-level expression of both the gltD and gltF genes is required for the induction of the Ntr enzymes under nitrogen-limiting conditions, indicating that the phenotype of the gltB insertion probably results from polarity on gltD and gltF. Third, glutamate-dependent repression of the glt operon appears to be mediated by the product of the gltF gene. Thus, the gltBDF operon of Escherichia coli is involved in induction of the so-called Ntr enzymes in response to nitrogen deprivation, as well as in glutamate biosynthesis.     

Characterization of a variant of carcinoembryonic antigen (CEA) using monoclonal and polyclonal anti-CEA antibodies

A variant of the carcinoembryonic antigen (CEA) with lower molecular weight than a CEA reference preparation has been separated from CEA. Using a polyclonal, spleen absorbed anti-CEA antiserum, the variant crossreacts with reference CEA in immunodiffusion. The CEA-activity of the variant has been demonstrated using an enzyme-immunoassay with monoclonal CEA specific antibodies. There is sufficient immunological evidence that this variant is a distinct antigen different from the crossreactive antigens described so far. The reactivity of the polyclonal anti-CEA antiserum with the CEA variant was abolished by absorption against the immobilized variant.     

Exome sequences and multi‐environment field trials elucidate the genetic basis of adaptation in barley

Broadening the genetic base of crops is crucial for developing varieties to respond to global agricultural challenges such as climate change. Here, we analysed a diverse panel of 371 domesticated lines of the model crop barley to explore the genetics of crop adaptation. We first collected exome sequence data and phenotypes of key life history traits from contrasting multi‐environment common garden trials. Then we applied refined statistical methods, including some based on exomic haplotype states, for genotype‐by‐environment (G×E) modelling. Sub‐populations defined from exomic profiles were coincident with barley's biology, geography and history, and explained a high proportion of trial phenotypic variance. Clear G×E interactions indicated adaptation profiles that varied for landraces and cultivars. Exploration of circadian clock‐related genes, associated with the environmentally adaptive days to heading trait (crucial for the crop's spread from the Fertile Crescent), illustrated complexities in G×E effect directions, and the importance of latitudinally based genic context in the expression of large‐effect alleles. Our analysis supports a gene‐level scientific understanding of crop adaption and leads to practical opportunities for crop improvement, allowing the prioritisation of genomic regions and particular sets of lines for breeding efforts seeking to cope with climate change and other stresses.     

Chaotic and stochastic dynamics of epileptiform-like activities in sclerotic hippocampus resected from patients with pharmacoresistant epilepsy

The types of epileptiform activity occurring in the sclerotic hippocampus with highest incidence are interictal-like events (II) and periodic ictal spiking (PIS). These activities are classified according to their event rates, but it is still unclear if these rate differences are consequences of underlying physiological mechanisms. Identifying new and more specific information related to these two activities may bring insights to a better understanding about the epileptogenic process and new diagnosis. We applied Poincaré map analysis and Recurrence Quantification Analysis (RQA) onto 35 in vitro electrophysiological signals recorded from slices of 12 hippocampal tissues surgically resected from patients with pharmacoresistant temporal lobe epilepsy. These analyzes showed that the II activity is related to chaotic dynamics, whereas the PIS activity is related to deterministic periodic dynamics. Additionally, it indicates that their different rates are consequence of different endogenous dynamics. Finally, by using two computational models we were able to simulate the transition between II and PIS activities. The RQA was applied to different periods of these simulations to compare the recurrences between artificial and real signals, showing that different ranges of regularity-chaoticity can be directly associated with the generation of PIS and II activities.     

Analysing the yeast complexome—the Complex Portal rising to the challenge

The EMBL-EBI Complex Portal is a knowledgebase of macromolecular complexes providing persistent stable identifiers. Entries are linked to literature evidence and provide details of complex membership, function, structure and complex-specific Gene Ontology annotations. Data are freely available and downloadable in HUPO-PSI community standards and missing entries can be requested for curation. In collaboration with Saccharomyces Genome Database and UniProt, the yeast complexome, a compendium of all known heteromeric assemblies from the model organism Saccharomyces cerevisiae, was curated. This expansion of knowledge and scope has led to a 50% increase in curated complexes compared to the previously published dataset, CYC2008. The yeast complexome is used as a reference resource for the analysis of complexes from large-scale experiments. Our analysis showed that genes coding for proteins in complexes tend to have more genetic interactions, are co-expressed with more genes, are more multifunctional, localize more often in the nucleus, and are more often involved in nucleic acid-related metabolic processes and processes where large machineries are the predominant functional drivers. A comparison to genetic interactions showed that about 40% of expanded co-complex pairs also have genetic interactions, suggesting strong functional links between complex members.     

Quantitative Changes in the Sleep EEG at Moderate Altitude (1630 m and 2590 m)

Background

Previous studies have observed an altitude-dependent increase in central apneas and a shift towards lighter sleep at altitudes >4000 m. Whether altitude-dependent changes in the sleep EEG are also prevalent at moderate altitudes of 1600 m and 2600 m remains largely unknown. Furthermore, the relationship between sleep EEG variables and central apneas and oxygen saturation are of great interest to understand the impact of hypoxia at moderate altitude on sleep.

Methods

Fourty-four healthy men (mean age 25.0±5.5 years) underwent polysomnographic recordings during a baseline night at 490 m and four consecutive nights at 1630 m and 2590 m (two nights each) in a randomized cross-over design.

Results

Comparison of sleep EEG power density spectra of frontal (F3A2) and central (C3A2) derivations at altitudes compared to baseline revealed that slow-wave activity (SWA, 0.8–4.6 Hz) in non-REM sleep was reduced in an altitude-dependent manner (∼4% at 1630 m and 15% at 2590 m), while theta activity (4.6–8 Hz) was reduced only at the highest altitude (10% at 2590 m). In addition, spindle peak height and frequency showed a modest increase in the second night at 2590 m. SWA and theta activity were also reduced in REM sleep. Correlations between spectral power and central apnea/hypopnea index (AHI), oxygen desaturation index (ODI), and oxygen saturation revealed that distinct frequency bands were correlated with oxygen saturation (6.4–8 Hz and 13–14.4 Hz) and breathing variables (AHI, ODI; 0.8–4.6 Hz).

Conclusions

The correlation between SWA and AHI/ODI suggests that respiratory disturbances contribute to the reduction in SWA at altitude. Since SWA is a marker of sleep homeostasis, this might be indicative of an inability to efficiently dissipate sleep pressure.     

Effects of Acute Exposure to Moderate Altitude on Vascular Function,Metabolism and Systemic Inflammation

Background

Travel to mountain areas is popular. However, the effects of acute exposure to moderate altitude on the cardiovascular system and metabolism are largely unknown.

Objectives

To investigate the effects of acute exposure to moderate altitude on vascular function, metabolism and systemic inflammation.

Methods

In 51 healthy male subjects with a mean (SD) age of 26.9 (9.3) years, oxygen saturation, blood pressure, heart rate, arterial stiffness, lipid profiles, low density lipoprotein (LDL) particle size, insulin resistance (HOMA-index), highly-sensitive C-reactive protein and pro-inflammatory cytokines were measured at 490 m (Zurich) and during two days at 2590 m, (Davos Jakobshorn, Switzerland) in randomized order. The largest differences in outcomes between the two altitudes are reported.

Results

Mean (SD) oxygen saturation was significantly lower at 2590 m, 91.0 (2.0)%, compared to 490 m, 96.0 (1.0)%, p<0.001. Mean blood pressure (mean difference +4.8 mmHg, p<0.001) and heart rate (mean difference +3.3 bpm, p<0.001) were significantly higher at 2590 m, compared to 490 m, but this was not associated with increased arterial stiffness. At 2590 m, lipid profiles improved (median difference triglycerides −0.14 mmol/l, p = 0.012, HDL +0.08 mmol/l, p<0.001, total cholesterol/HDL-ratio −0.25, p = 0.001), LDL particle size increased (median difference +0.45 nm, p = 0.048) and hsCRP decreased (median difference −0.18 mg/l, p = 0.024) compared to 490 m. No significant change in pro-inflammatory cytokines or insulin resistance was observed upon ascent to 2590 m.

Conclusions

Short-term stay at moderate altitude is associated with increased blood pressure and heart rate likely due to augmented sympathetic activity. Exposure to moderate altitude improves the lipid profile and systemic inflammation, but seems to have no significant effect on glucose metabolism.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01130948","term_id":"NCT01130948"}}NCT01130948