3D Brain Atlas Reconstructor Service—Online Repository of Three-Dimensional Models of Brain Structures

Brain atlases are important tools of neuroscience. Traditionally prepared in paper book format, more and more commonly they take digital form which extends their utility. To simplify work with different atlases, to lay the ground for developing universal tools which could abstract from the origin of the atlas, efforts are being made to provide common interfaces to these atlases. 3D Brain Atlas Reconstructor service (3dBARs) described here is a repository of digital representations of different brain atlases in CAF format which we recently proposed and a repository of 3D models of brain structures. A graphical front-end is provided for creating and viewing the reconstructed models as well as the underlying 2D atlas data. An application programming interface (API) facilitates programmatic access to the service contents from other websites. From a typical user’s point of view, 3dBARs offers an accessible way to mine publicly available atlasing data with a convenient browser based interface, without the need to install extra software. For a developer of services related to brain atlases, 3dBARs supplies mechanisms for enhancing functionality of other software. The policy of the service is to accept new datasets as delivered by interested parties and we work with the researchers who obtain original data to make them available to the neuroscience community at large. The functionality offered by the 3dBARs situates it at the core of present and future general atlasing services tying it strongly to the global atlasing neuroinformatics infrastructure.     

Variability of soil microbial properties: Effects of sampling, handling and storage

We investigated the effect of soil spatial variability within the sampling site scale, the effects of sample sieving (1, 2 and 4 mm), and storage conditions up to 32 weeks (wet at 4 °C, −20 °C and air dried) on microbial biomass C, respiration, ammonification and nitrification activities in arable, grassland and forest soil. In general, all results were dependent on soil type. Arable soil showed the highest spatial variability, followed by grassland and forest soil. Sieving did not cause large differences; however, higher biomass C and respiration activity were observed in the 1 mm than in the 4 mm fraction. Storage at 4 °C seemed to be the most appropriate up to 8 weeks showing only minor changes of microbial parameters. Freezing of soils resulted in large increase of respiration. Dried storage indicated disruption of microbial communities even after 2 weeks.     

Crohn's disease: Clinical–surgical questions and imaging answers

Crohn's disease is an inflammatory bowel disease (IBD) characterized by a relapsing clinical pattern that typically affects people during their adult and economically productive lives. Affected patients require clinical follow-up because of the periodic flare-up of the disease and of the risk of long-term complications. Extensive diagnostic procedures, medical and surgical treatments are often needed over a lifetime. The challenge posed by the management of IBD is better faced by a multidisciplinary team that includes health care providers with complementary diagnostic or therapeutic skills. The team is expected to provide the best practice to manage IBD by defining a realistic “diagnostic and therapeutic pathway” for the patients to follow based on the locally available professional, structural and technological resources. For such a “pathway” the correct questions and answers are essential. Sometimes it is not easy to make sense out of these questions. To ask a right question is not simple. Of course, different surgeons and gastroenterologists ask different questions. If radiologists want to choose the right imaging method, they must know these questions. There exist a simple equation: good question = correct imaging method = right answer.     

Enkephalin degradation in serum of patients with inflammatory bowel diseases

Background

Inflammatory bowel diseases (IBD) are a group of chronic and recurrent gastrointestinal disorders that are difficult to control. Recently, a new IBD therapy based on the targeting of the endogenous opioid system has been proposed. Consequently, due to the fact that endogenous enkephalins have an anti-inflammatory effect, we aimed at investigating the degradation of serum enkephalin (Met- and Leu-enkephalin) in patients with IBD.

MNU-induced mammary gland carcinogenesis: chemopreventive and therapeutic effects of vitamin D and Seocalcitol on selected regulatory vitamin D receptor pathways

The effects of administration of vitamin D₃ and Seocalcitol on MNU-induced carcinogenesis of mammary gland in Sprague-Dawley rats have been investigated. Administration of both substances in a weekly dose of 7 μg/kg caused prolonged latency of mammary gland tumors. The latency of tumors was markedly prolonged for 30-40 days by Seocalcitol. Using PET analysis, reduction in [¹⁸F]2-fluoro-2-deoxy-d-glucose (FDG) uptake or tumor volume in tumors chemopreventively treated with vitamin D₃ were detected in MNU-induced tumors, vitamin D₃ reduced expression of 25-hydroxylase (25OHase) (p < 0.01) and 24-hydroxylase (24OHase) (p < 0.01) and Seocalcitol 24OHase. Positive regulation of 25OHase mRNA level after the treatment with vitamin D₃ was observed in liver, while in kidney, vitamin D₃ and Seocalcitol induced expression of 24OHase was significant. Our observations indicate a cross talk between respective pathways of VDR, RARs/RXRs, TRs and ERs in carcinogenesis process.     

The role of morphine in regulation of cancer cell growth

Morphine is considered the “gold standard” for relieving pain and is currently one of the most effective drugs available clinically for the management of severe pain associated with cancer. In addition to its use in the treatment of pain, morphine appears to be important in the regulation of neoplastic tissue. Although morphine acts directly on the central nervous system to relieve pain, its activities on peripheral tissues are responsible for many of the secondary complications. Therefore, understanding the impact, other than pain control, of morphine on cancer treatment is extremely important. The effect of morphine on tumor growth is still contradictory, as both growth-promoting and growth-inhibiting effects have been observed. Accumulating evidence suggests that morphine can affect proliferation and migration of tumor cells as well as angiogenesis. Various signaling pathways have been suggested to be involved in these extra-analgesic effects of morphine. Suppression of immune system by morphine is an additional complication. This review provides an update on the influence of morphine on the growth and migration potential of tumor cells.     

Effect of potent endomorphin degradation blockers on analgesic and antidepressant-like responses in mice

The biological effects of endomorphins (EMs) are short-lasting due to their rapid degradation by endogenous enzymes. Competing enzymatic degradation is an approach to prolong EM bioavailability. In the present study, a series of tetra- and tripeptides of similar to EMs structure was synthesized and tested in vitro and in vivo for their ability to inhibit degradation of EMs. The obtained results indicated that, among the series of analogs, the tetrapeptide Tyr–Pro–d–ClPhe–Phe–NH₂ and the tripeptide Tyr–Pro–Ala–NH₂, which did not bind to the μ-opioid receptors, were potent inhibitors of EM catabolism in rat brain homogenate. In vivo, these two peptides significantly prolonged the analgesic and antidepressant-like effects, induced by exogenous EMs, by blocking EM degrading enzymes. These new potent inhibitors may therefore increase the level and the half life of endogenous EMs and could be used in a new therapeutic strategy against pain and mood disorders, based on increasing of EM bioavailability.     

Olomoucine II and purvalanol A inhibit ABCG2 transporter in vitro and in situ and synergistically potentiate cytostatic effect of mitoxantrone

Inhibition of cyclin-dependent kinases by specific small molecules, purine cyclin-dependent kinase inhibitors (CDKi), has become a promising strategy for cancer treatment. Although pharmacodynamic properties of these compounds have been studied extensively, their pharmacokinetic behavior has not been addressed in detail. In this study, we investigated possible inhibitory effect of five purine CDKi on breast cancer resistance protein (ABCG2) transport activity employing in vitro transport and accumulation methods in MCDKII cells transduced with human ABCG2. Hoechst 33342 and glyburide were used as model ABCG2 substrates for these experiments. In addition, in situ method of dually perfused rat term placenta was utilized to confirm our in vitro results at the organ level. Fumitremorgin C was used as a model inhibitor of ABCG2 for comparison purposes. We demonstrate significant inhibition of ABCG2 by four of the five CDKi tested. Regarding their ABCG2-inhibitory potencies, the investigated compounds can be ranked as follows: purvalanol A>olomoucine II≈fumitremorgin C>roscovitine≈bohemine, with slight differences among substrates, concentrations and methods used. Based on our findings, it is reasonable to expect a substantial impact of the studied CDKi on the pharmacokinetic and pharmacodynamic behavior of concomitantly administered ABCG2 substrates. Moreover, using combination index method of Chou-Talalay, we confirmed that the strongest inhibitors, purvalanol A and olomoucine II, can synergistically potentiate cytostatic effect of mitoxantrone, an ABCG2 substrate, in ABCG2 expressing cell lines.     

An fMRI study of caring vs self-focus during induced compassion and pride

This study examined neural activation during the experience of compassion, an emotion that orients people toward vulnerable others and prompts caregiving, and pride, a self-focused emotion that signals individual strength and heightened status. Functional magnetic resonance images (fMRI) were acquired as participants viewed 55 s continuous sequences of slides to induce either compassion or pride, presented in alternation with sequences of neutral slides. Emotion self-report data were collected after each slide condition within the fMRI scanner. Compassion induction was associated with activation in the midbrain periaqueductal gray (PAG), a region that is activated during pain and the perception of others' pain, and that has been implicated in parental nurturance behaviors. Pride induction engaged the posterior medial cortex, a region that has been associated with self-referent processing. Self-reports of compassion experience were correlated with increased activation in a region near the PAG, and in the right inferior frontal gyrus (IFG). Self-reports of pride experience, in contrast, were correlated with reduced activation in the IFG and the anterior insula. These results provide preliminary evidence towards understanding the neural correlates of important interpersonal dimensions of compassion and pride. Caring (compassion) and self-focus (pride) may represent core appraisals that differentiate the response profiles of many emotions.