Schistosoma mansoni infection enhances host portal vein contraction: role of potassium channels and p38 MAP kinase

Murine Schistosoma mansoni infection is related to an increased contraction of portal vein in response to 5-hydroxytryptamine (5-HT). The present study addressed a putative alteration of ion channels and enzymes involved in vascular contraction. In control group, either inhibition of K+ channels sensitive to ATP (K(ATP)) or Ca2+ (BK(Ca)) increased 5-HT-induced contraction, but the same did not occur in infected mice. On the other hand, inhibition of p38 MAP kinase markedly decreased the vascular contraction to 5-HT in the infected mice with minor effects in the control group. Accordingly, we observed a higher density of phospho-p38 MAP kinase, that refers to the fully active state of the enzyme, in portal veins from infected mice as compared to control animals. These results suggest that the reduced function of K(ATP) and BK(Ca) channels along with an increased contribution of p38 MAP kinase contribute to the increased contraction of portal veins to 5-HT observed in murine schistosomiasis.     

Characterizing the spatio-temporal behavior of cell populations through image auto- and cross-correlation microscopy

We propose two methods for characterizing the spatio-temporal behavior of cell populations in culture. The first method, image auto-correlation microscopy (IACM), allows us to characterize the variation in the number of objects as a function of time, thus enabling the quantification of the clustering properties of cell populations to be performed. The second method, image cross-correlation microscopy (ICCM), allows us to characterize the migration properties of cell populations. The latter method does not require estimation or measurement of the trajectories of individual cells, which is very demanding when populations of >100 cells are examined. The capabilities of the two methods are demonstrated with simulated cell populations, and their usefulness is illustrated with experiments involving invasive and noninvasive tumor cell populations.     

Antinociceptive efficacy of lacosamide in the monosodium iodoacetate rat model for osteoarthritis pain

The etiology of osteoarthritis is multifactorial, with inflammatory, metabolic, and mechanical causes. Pain in osteoarthritis is initiated by mild intra-articular inflammation and degeneration of articular cartilage and subchondral bone. The principle of treatment with acetaminophen or non-steroidal anti-inflammatory drugs is to reduce pain and improve joint function. Recently, animal models for osteoarthritic pain behavior have been established. The most frequently used rat model for analyzing properties of drugs on the pathology of osteoarthritis is the injection of the metabolic inhibitor monosodium iodoacetate into the joint, which inhibits the activity of glyceraldehyde-3-phosphate dehydrogenase in chondrocytes. Here, we characterize the effect on pain behavior of lacosamide, a member of a family of functionalized amino acids that are analogues of endogenous amino acids and D-serine, in the monosodium iodoacetate rat model for osteoarthritis in comparison to diclofenac and morphine. Lacosamide (3, 10, and 30 mg/kg) was able to reduce secondary mechanical allodynia and hyperalgesia similarly to morphine (3 mg/kg). In contrast, diclofenac (30 mg/kg) was only effective in reducing secondary mechanical hyperalgesia. During the first week, pain is induced mainly by inflammation in the iodoacetate model, but afterwards inflammation plays only a minor role in pain. Lacosamide was able to inhibit pain at days 3, 7 and 14 after induction of arthritis. This shows that lacosamide is able to reduce pain behavior induced by multiple mechanisms in animals.     

Hybridization and polyploidization effects on LTR-retrotransposon activation in potato genome

Hybridization and polyploidization are major forces in plant evolution and potatoes are not an exception. It is proposed that the proliferation of Long Terminal Repeat-retrotransposons (LTR-RT) is related to genome reorganization caused by hybridization and/or polyploidization. The main purpose of the present work was to evaluate the effect of interspecific hybridization and polyploidization on the activation of LTR-RT. We evaluated the proliferation of putative active LTR-RT in a diploid hybrid between the cultivated potato Solanum tuberosum and the wild diploid potato species S. kurtzianum, allotetraploid lines derived from this interspecific hybrid and S. kurtzianum autotetraploid lines (ktz-autotetraploid) using the S-SAP (sequence-specific amplified polymorphism) technique and normalized copy number determination by qPCR. Twenty-nine LTR-RT copies were activated in the hybrid and present in the allotetraploid lines. Major LTR-RT activity was detected in Copia-27, Copia-12, Copia-14 and, Gypsy-22. According to our results, LTR-RT copies were activated principally in the hybrid, there was no activation in allotetraploid lines and only one copy was activated in the autotetraploid.

     

Identification of Cdk targets that control cytokinesis

The final event of the eukaryotic cell cycle is cytokinesis, when two new daughter cells are born. How the timing and execution of cytokinesis is controlled is poorly understood. Here, we show that downregulation of cyclin-dependent kinase (Cdk) activity, together with upregulation of its counteracting phosphatase Cdc14, controls each of the sequential steps of cytokinesis, including furrow ingression, membrane resolution and cell separation in budding yeast. We use phosphoproteome analysis of mitotic exit to identify Cdk targets that are dephosphorylated at the time of cytokinesis. We then apply a new and widely applicable tool to generate conditionally phosphorylated proteins to identify those whose dephosphorylation is required for cytokinesis. This approach identifies Aip1, Ede1 and Inn1 as cytokinetic regulators. Our results suggest that cytokinesis is coordinately controlled by the master cell cycle regulator Cdk together with its counteracting phosphatase and that it is executed by concerted dephosphorylation of Cdk targets involved in several cell biological processes.     

Effects of general,specific and combined warm-up on explosive muscular performance

The purpose of this study was to compare the acute effects of general, specific and combined warm-up (WU) on explosive performance. Healthy male (n = 10) subjects participated in six WU protocols in a crossover randomized study design. Protocols were: passive rest (PR; 15 min of passive rest), running (Run; 5 min of running at 70% of maximum heart rate), stretching (STR; 5 min of static stretching exercise), jumping [Jump; 5 min of jumping exercises – 3x8 countermovement jumps (CMJ) and 3x8 drop jumps from 60 cm (DJ60)], and combined (COM; protocols Run+STR+Jump combined). Immediately before and after each WU, subjects were assessed for explosive concentric-only (i.e. squat jump – SJ), slow stretch-shortening cycle (i.e. CMJ), fast stretch-shortening cycle (i.e. DJ60) and contact time (CT) muscle performance. PR significantly reduced SJ performance (p =0.007). Run increased SJ (p =0.0001) and CMJ (p =0.002). STR increased CMJ (p =0.048). Specific WU (i.e. Jump) increased SJ (p =0.001), CMJ (p =0.028) and DJ60 (p =0.006) performance. COM increased CMJ performance (p =0.006). Jump was superior in SJ performance vs. PR (p =0.001). Jump reduced (p =0.03) CT in DJ60. In conclusion, general, specific and combined WU increase slow stretch-shortening cycle (SSC) muscle performance, but only specific WU increases fast SSC muscle performance. Therefore, to increase fast SSC performance, specific fast SSC muscle actions must be included during the WU.     

EpiBrainRad: an epidemiologic study of the neurotoxicity induced by radiotherapy in high grade glioma patients

Background

Radiotherapy is one of the most important treatments of primary and metastatic brain tumors. Unfortunately, it can involve moderate to severe complications among which leukoencephalopathy is very frequent and implies cognitive deficits such as memory, attention and executive dysfunctions. However, the incidence of this complication is not well established and the risk factors and process are poorly understood. The main objective of the study is to improve knowledge on radio-induced leukoencephalopathy based on pluridisciplinar approaches combining cognitive, biologic, imagery and dosimetric investigations.

Method/Design

The EpiBrainRad study is a prospective cohort study including newly diagnosed high grade gliomas patients treated by radiotherapy and concomitant-adjuvant temozolomide chemotherapy. Patients are included between their surgery and first day of radio-chemotherapy, and the follow-up lasts for 3 years after treatment. Cognitive functioning assessments, specific blood biomarkers measures and magnetic resonance imagery are performed at different moment during the follow-up, and a specific dosimetric assessment of organs involved in the beam fields is performed. Firstly, leukoencephalopathy incidence rate will be estimated in this population. Secondly, correlations between cognitive impairments and dosimetry, biomarkers ranges and anomalies on imagery will be analyzed in order to better understand the onset and evolution of cognitive decrement associated with radiotherapy. Furthermore, a new cognitive test, quickly and easily performed, will be studied to determine its sensibility to detect leukoencephalopathy decrement.

Discussion

With an original multidisciplinary approach, the EpiBrainRad study aims to improve knowledge on radio-induced leukoencephalopathy in order to improve its early diagnosis and prevention. The main challenge is to preserve quality-of-life after cancer treatments which imply to study the incidence of radiation-induced complications and their associated risk factors.

Trial Registration

NCT02544178