Limited water stress modulates expression of circadian clock genes in Brachypodium distachyon roots.

Organisms have evolved a circadian clock for the precise timing of their biological processes. Studies primarily on model dicots have shown the complexity of the inner timekeeper responsible for maintaining circadian oscillation in plants and have highlighted that circadian regulation is more than relevant to a wide range of biological processes, especially organ development and timing of flowering. Contribution of the circadian clock to overall plant fitness and yield has also long been known. Nevertheless, the organ- and species-specific functions of the circadian clock and its relation to stress adaptation have only recently been identified. Here we report transcriptional changes of core clock genes of the model monocot Brachypodium distachyon under three different light regimes (18:6 light:dark, 24:0 light and 0:24 dark) in response to mild drought stress in roots and green plant parts. Comparative monitoring of core clock gene expression in roots and green plant parts has shown that both phase and amplitude of expression in the roots of Brachypodium plants differ markedly from those in the green plant parts, even under well-watered conditions. Moreover, circadian clock genes responded to water depletion differently in root and shoot. These results suggest an organ-specific form and functions of the circadian clock in Brachypodium roots.

Clinical parameters predict the effect of bilateral subthalamic stimulation on dynamic balance parameters during gait in Parkinson's disease.

We investigated the effect of deep brain stimulation on dynamic balance during gait in Parkinson's disease with motion sensor measurements and predicted their values from disease-related factors. We recruited twenty patients with Parkinson's disease treated with bilateral subthalamic stimulation for at least 12 months and 24 healthy controls. Six monitors with three-dimensional gyroscopes and accelerometers were placed on the chest, the lumbar region, the two wrists, and the shins. Patients performed the instrumented Timed Up and Go test in stimulation OFF, stimulation ON, and right- and left-sided stimulation ON conditions. Gait parameters and dynamic balance parameters such as double support, peak turn velocity, and the trunk's range of motion and velocity in three dimensions were analyzed. Age, disease duration, the time elapsed after implantation, the Hoehn-Yahr stage before and after the operation, the levodopa, and stimulation responsiveness were reported. We individually calculated the distance values of stimulation locations from the subthalamic motor center in three dimensions. Sway values of static balance were collected. We compared the gait parameters in the OFF and stimulation ON states and controls. With cluster analysis and a machine-learning-based multiple regression method, we explored the predictive clinical factors for each dynamic balance parameter (with age as a confounder). The arm movements improved the most among gait parameters due to stimulation and the horizontal and sagittal trunk movements. Double support did not change after switching on the stimulation on the group level and did not differ from control values. Individual changes in double support and horizontal range of trunk motion due to stimulation could be predicted from the most disease-related factors and the severity of the disease; the latter also from the stimulation-related changes in the static balance parameters. Physiotherapy should focus on double support and horizontal trunk movements when treating patients with subthalamic deep brain stimulation.

Factors affecting postural instability after more than one-year bilateral subthalamic stimulation in Parkinson's disease: A cross-sectional study.

BACKGROUND: Balance impairment in Parkinson's disease is multifactorial and its changes due to subthalamic stimulation vary in different studies. OBJECTIVE: We aimed to analyze the combination of predictive clinical factors of balance impairment in patients with Parkinson's disease treated with bilateral subthalamic stimulation for at least one year. METHODS: We recruited 24 patients with Parkinson's disease treated with bilateral subthalamic stimulation and 24 healthy controls. They wore an Opal monitor (APDM Inc.) consisting of three-dimensional gyroscopes and accelerometers in the lumbar region. We investigated four stimulation conditions (bilateral stimulation OFF, bilateral stimulation ON, and unilateral right- and left-sided stimulation ON) with four tests: stance on a plain ground with eyes open and closed, stance on a foam platform with eyes open and closed. Age, disease duration, the time elapsed after implantation, levodopa, and stimulation responsiveness were analyzed. The distance of stimulation location from the subthalamic motor center was calculated individually in each plane of the three dimensions. We analyzed the sway values in the four stimulation conditions in the patient group and compared them with the control values. We explored factor combinations (with age as confounder) in the patient group predictive for imbalance with cluster analysis and a machine-learning-based multiple regression method. RESULTS: Sway combined from the four tasks did not differ in the patients and controls on a group level. The combination of the disease duration, the preoperative levodopa responsiveness, and the stimulation responsiveness predicted individual stimulation-induced static imbalance. The more affected patients had more severe motor symptoms; primarily, the proprioceptive followed by visual sensory feedback loss provoked imbalance in them when switching on the stimulation. CONCLUSIONS: The duration of the disease, the severity of motor symptoms, the levodopa responsiveness, and additional sensory deficits should be carefully considered during preoperative evaluation to predict subthalamic stimulation-induced imbalance in Parkinson's disease.

Frequency-specific network activity predicts bradykinesia severity in Parkinson's disease.

OBJECTIVE: Bradykinesia has been associated with beta and gamma band interactions in the basal ganglia-thalamo-cortical circuit in Parkinson's disease. In this present cross-sectional study, we aimed to search for neural networks with electroencephalography whose frequency-specific actions may predict bradykinesia. METHODS: Twenty Parkinsonian patients treated with bilateral subthalamic stimulation were first prescreened while we selected four levels of contralateral stimulation (0: OFF, 1-3: decreasing symptoms to ON state) individually, based on kinematics. In the screening period, we performed 64-channel electroencephalography measurements simultaneously with electromyography and motion detection during a resting state, finger tapping, hand grasping tasks, and pronation-supination of the arm, with the four levels of contralateral stimulation. We analyzed spectral power at the low (13-20 Hz) and high (21-30 Hz) beta frequency bands and low (31-60 Hz) and high (61-100 Hz) gamma frequency bands using the dynamic imaging of coherent sources. Structural equation modelling estimated causal relationships between the slope of changes in network beta and gamma activities and the slope of changes in bradykinesia measures. RESULTS: Activity in different subnetworks, including predominantly the primary motor and premotor cortex, the subthalamic nucleus predicted the slopes in amplitude and speed while switching between stimulation levels. These subnetwork dynamics on their preferred frequencies predicted distinct types and parameters of the movement only on the contralateral side. DISCUSSION: Concurrent subnetworks affected in bradykinesia and their activity changes in the different frequency bands are specific to the type and parameters of the movement; and the primary motor and premotor cortex are common nodes.

SUMOylation of PHYTOCHROME INTERACTING FACTOR 3 promotes photomorphogenesis in Arabidopsis thaliana.

In Arabidopsis thaliana, phytochrome B (phyB) is the dominant receptor of photomorphogenic development under red light. Phytochrome B interacts with a set of downstream regulatory proteins, including PHYTOCHROME INTERACTING FACTOR 3 (PIF3). The interaction between PIF3 and photoactivated phyB leads to the rapid phosphorylation and degradation of PIF3 and also to the degradation of phyB, events which are required for proper photomorphogenesis. Here we report that PIF3 is SUMOylated at the Lys13 (K13) residue and that we could detect this posttranslational modification in a heterologous experimental system and also in planta. We also found that the SUMO acceptor site mutant PIF3(K13R) binds more strongly to the target promoters than its SUMOylated, wild-type counterpart. Seedlings expressing PIF3(K13R) show an elongated hypocotyl response, elevated photoprotection and higher transcriptional induction of red-light responsive genes compared with plantlets expressing wild-type PIF3. These observations are supported by the lower level of phyB in plants which possess only PIF3(K13R), indicating that SUMOylation of PIF3 also alters photomorphogenesis via the regulation of phyB levels. In conclusion, whereas SUMOylation is generally connected to different stress responses, it also fine-tunes light signalling by reducing the biological activity of PIF3, thus promoting photomorphogenesis.

Histone H3.3G34-Mutant Interneuron Progenitors Co-opt PDGFRA for Gliomagenesis.

Histone H3.3 glycine 34 to arginine/valine (G34R/V) mutations drive deadly gliomas and show exquisite regional and temporal specificity, suggesting a developmental context permissive to their effects. Here we show that 50% of G34R/V tumors (n = 95) bear activating PDGFRA mutations that display strong selection pressure at recurrence. Although considered gliomas, G34R/V tumors actually arise in GSX2/DLX-expressing interneuron progenitors, where G34R/V mutations impair neuronal differentiation. The lineage of origin may facilitate PDGFRA co-option through a chromatin loop connecting PDGFRA to GSX2 regulatory elements, promoting PDGFRA overexpression and mutation. At the single-cell level, G34R/V tumors harbor dual neuronal/astroglial identity and lack oligodendroglial programs, actively repressed by GSX2/DLX-mediated cell fate specification. G34R/V may become dispensable for tumor maintenance, whereas mutant-PDGFRA is potently oncogenic. Collectively, our results open novel research avenues in deadly tumors. G34R/V gliomas are neuronal malignancies where interneuron progenitors are stalled in differentiation by G34R/V mutations and malignant gliogenesis is promoted by co-option of a potentially targetable pathway, PDGFRA signaling.

[Prognostic significance of invasion in glioblastoma]. / Az inváziós spektrum prognosztikai jelentôsége glioblastomában.

BACKGROUND AND PURPOSE: Glioblastoma is the most common malignant CNS tumor, its surgical removal is hindered by the tumors invasive nature, while current anti-tumor therapies show limited effectiveness - mean overall survival is 16-24 months. Some patients show minimal response towards standard oncotherapy, however there are no routinely available prognostic and predictive markers in clinical practice to identify the background of mentioned differences in prognosis. This research aims to identify the prognostic significance of invasion-related extracellular (ECM) components. METHODS: Patient groups with different prognoses were created (OS: group A <16 months, group B > 16 months), and internationally recognized prognostic markers (IDH1 mutation and MGMT promoter hyper-methylation) were tested in the flash-frozen tumor samples. Furthermore, the mRNA levels of 46 invasion-related ECM molecules were measured. RESULTS: Clinical data of the patients who have been operated on at the University of Debrecen Clinical Center Department of Neurosurgery and treated at the Department of Clinical Oncology showed no significant differences except for survival data (OS and PFS), and reoperation rate. All samples were IDH wild type. MGMT promoter hypermethylation rate showed significant differences (28.6% vs 68.8%). The expressional pattern of the invasion-related ECM molecules, i.e. the invasion spectrum also showed major differences, integrin ß2, cadherin-12, FLT4/VEGFR-3 and versican molecules having signficantly different mRNA levels. The accuracy of the inivasion spectrum was tested by statistical classifier, 83.3% of the samples was sorted correctly, PPV was 0.93. CONCLUSION: The difference found in the reoperation rate when comparing different prognostic groups aligns with literature data. MGMG promoter region methylation data in Hungarian samples has not been published yet, and further confirming current knowledge urges the implementation of MGMT promoter analysis in clinical practice. Studying the invasion spectrum provides extra information on tumors, as a prognostic marker it helps recognizing more aggressive tumors, and calls attention to the necessity of using anti-invasive agents in GBM therapies in the future.

Elevated Pro-Inflammatory Cell-Free MicroRNA Levels in Cerebrospinal Fluid of Premature Infants after Intraventricular Hemorrhage.

Intraventricular hemorrhage (IVH) represents a high risk of neonatal mortality and later neurodevelopmental impairment in prematurity. IVH is accompanied with inflammation, hemolysis, and extracellular hemoglobin (Hb) oxidation. However, microRNA (miRNA) expression in cerebrospinal fluid (CSF) of preterm infants with IVH has been unknown. Therefore, in the present study, candidate pro-inflammatory cell-free miRNAs were analyzed in CSF samples from 47 preterm infants with grade III or IV IVH vs. clinical controls (n = 14). miRNAs were quantified by RT-qPCR, normalized to "spike-in" cel-miR-39. Oxidized Hb and total heme levels were determined by spectrophotometry as well as IL-8, VCAM-1, ICAM-1, and E-selectin concentrations by ELISA. To reveal the origin of the investigated miRNAs, controlled hemolysis experiments were performed in vitro; in addition, human choroid plexus epithelial cell (HCPEpiC) cultures were treated with metHb, ferrylHb, heme, or TNF-α to replicate IVH-triggered cellular conditions. Levels of miR-223, miR-155, miR-181b, and miR-126 as well as Hb metabolites along with IL-8 were elevated in CSF after the onset of IVH vs. controls. Significant correlations were observed among the miRNAs, oxidized Hb forms, and the soluble adhesion molecules. During the post-IVH follow-up, attenuated expression of miRNAs and protein biomarkers in CSF was observed upon elimination of Hb metabolites. These miRNAs remained unaffected by a series of artificially induced hemolysis, which excluded red blood cells as their origin, while stimulation of HCPEpiCs with oxidized Hb fractions and heme resulted in increased extracellular miRNA levels in the cell culture supernatant. Overall, the hemorrhage-induced CSF miRNAs reflected inflammatory conditions as potential biomarkers in preterm IVH.

Intraoperative electrophysiology in children - Single institute experience of 96 examinations.

AIM: To summarize our experience gathered during the use of different intraoperative electrophysiological modalities in children. MATERIALS AND METHODS: We analyzed the data collected from 96 pediatric neurosurgical interventions. During the operations, we used a combination of intraoperative electrophysiological examinations tailored to the actual pathologies. The modalities included cortical and white matter mapping, cranial nerve and cranial nerve nucleus stimulation, motor evoked potential (MEP), somatosensory evoked potential (SSEP), peripheral nerve stimulation, bulbocavernosus reflex, and a special setup for selective dorsal rhizotomy. RESULTS: The success ratio of the different modalities varied between 25% and 100%. All the applied methods could be used in children. CONCLUSION: Although the application of certain intraoperative techniques could be limited due to the ongoing developmental and maturation processes in childhood, we can not exclude the possibility of successful recording in any modality. Thus, we recommend to apply all the available methods in children bearing in mind that the success ratio might be lower than that in the adult population.

Formation and Detection of Highly Oxidized Hemoglobin Forms in Biological Fluids during Hemolytic Conditions.

Hemolytic diseases are characterized by an accelerated breakdown of red blood cells (RBCs) and the release of hemoglobin (Hb). Following, RBC lysis Hb oxidation occurs with the formation of different redox states of Hb (metHb and ferrylHb) and the release of heme. ferrylHb is unstable and decomposes to metHb with the concomitant formation of globin radicals and eventually covalently crosslinked Hb multimers. The goal of the present study was to determine the concentrations of the different redox states of Hb in biological samples during hemolytic conditions. We used plasma and urine samples of mice with intravascular hemolysis and human cerebrospinal fluid (CSF) samples following intraventricular hemorrhage. Because ferrylHb is highly unstable, we also addressed the fate of this species. metHb and free heme time-dependently accumulate in plasma and CSF samples following intravascular hemolysis and intraventricular hemorrhage, respectively. ferrylHb is hardly detectable in the biological samples during hemolytic conditions. Under in vitro conditions, ferrylHb decomposes quickly to metHb, which process is associated with the formation of covalently crosslinked Hb multimers. We detected these covalently crosslinked Hb multimers in plasma, urine, and CSF samples during hemolytic conditions. Because globin modification is specific for these Hb forms, we propose to call this heterogeneous form of Hb produced during ferrylHb decomposition as globin-modified oxidized Hb (gmoxHb). Understanding the formation and the contribution of gmoxHb species to the pathogenesis of hemolytic conditions could have therapeutic implications in the treatment of hemolytic diseases.

The Role of Hemoglobin Oxidation Products in Triggering Inflammatory Response Upon Intraventricular Hemorrhage in Premature Infants.

Intraventricular hemorrhage (IVH) is a frequent complication of prematurity that is associated with high neonatal mortality and morbidity. IVH is accompanied by red blood cell (RBC) lysis, hemoglobin (Hb) oxidation, and sterile inflammation. Here we investigated whether extracellular Hb, metHb, ferrylHb, and heme contribute to the inflammatory response after IVH. We collected cerebrospinal fluid (CSF) (n = 20) from premature infants with grade III IVH at different time points after the onset of IVH. Levels of Hb, metHb, total heme, and free heme were the highest in CSF samples obtained between days 0 and 20 after the onset of IVH and were mostly non-detectable in CSF collected between days 41 and 60 of post-IVH. Besides Hb monomers, we detected cross-linked Hb dimers and tetramers in post-IVH CSF samples obtained in days 0-20 and 21-40, but only Hb tetramers were present in CSF samples obtained after 41-60 days. Vascular cell adhesion molecule-1 (VCAM-1) and interleukin-8 (IL-8) levels were higher in CSF samples obtained between days 0 and 20 than in CSF collected between days 41 and 60 of post-IVH. Concentrations of VCAM-1, intercellular adhesion molecule-1 (ICAM-1), and IL-8 strongly correlated with total heme levels in CSF. Applying the identified heme sources on human brain microvascular endothelial cells revealed that Hb oxidation products and free heme contribute to the inflammatory response. We concluded that RBC lysis, Hb oxidation, and heme release are important components of the inflammatory response in IVH. Pharmacological interventions targeting cell-free Hb, Hb oxidation products, and free heme could have potential to limit the neuroinflammatory response following IVH.

Cranial and ventricular size following shunting or endoscopic third ventriculostomy (ETV) in infants with aqueductal stenosis: further insights from the International Infant Hydrocephalus Study (IIHS).

PURPOSE: The craniometrics of head circumference (HC) and ventricular size are part of the clinical assessment of infants with hydrocephalus and are often utilized in conjunction with other clinical and radiological parameters to determine the success of treatment. We aimed to assess the effect of endoscopic third ventriculostomy (ETV) and shunting on craniometric measurements during the follow-up of a cohort of infants with symptomatic triventricular hydrocephalus secondary to aqueductal stenosis. METHODS: We performed a post hoc analysis of data from the International Infant Hydrocephalus Study (IIHS)-a prospective, multicenter study of infants (< 24 months old) with hydrocephalus from aqueductal stenosis who were treated with either an ETV or shunt. During various stages of a 5-year follow-up period, the following craniometrics were measured: HC, HC centile, HC z-score, and frontal-occipital horn ratio (FOR). Data were compared in an analysis of covariance, adjusting for baseline variables including age at surgery and sex. RESULTS: Of 158 enrolled patients, 115 underwent an ETV, while 43 received a shunt. Both procedures led to improvements in the mean HC centile position and z-score, a trend which continued until the 5-year assessment point. A similar trend was noted for FOR which was measured at 12 months and 3 years following initial treatment. Although the values were consistently higher for ETV compared with shunt, the differences in HC value, centile, and z-score were not significant. ETV was associated with a significantly higher FOR compared with shunting at 12 months (0.52 vs 0.44; p = 0.002) and 3 years (0.46 vs 0.38; p = 0.03) of follow-up. CONCLUSION: ETV and shunting led to improvements in HC centile, z-score, and FOR measurements during long-term follow-up of infants with hydrocephalus secondary to aqueductal stenosis. Head size did not significantly differ between the treatment groups during follow-up, however ventricle size was greater in those undergoing ETV when measured at 1 and 3 years following treatment.

Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma.

In cancer, recurrent somatic single-nucleotide variants-which are rare in most paediatric cancers-are confined largely to protein-coding genes1-3. Here we report highly recurrent hotspot mutations (r.3A>G) of U1 spliceosomal small nuclear RNAs (snRNAs) in about 50% of Sonic hedgehog (SHH) medulloblastomas. These mutations were not present across other subgroups of medulloblastoma, and we identified these hotspot mutations in U1 snRNA in only <0.1% of 2,442 cancers, across 36 other tumour types. The mutations occur in 97% of adults (subtype SHHδ) and 25% of adolescents (subtype SHHα) with SHH medulloblastoma, but are largely absent from SHH medulloblastoma in infants. The U1 snRNA mutations occur in the 5' splice-site binding region, and snRNA-mutant tumours have significantly disrupted RNA splicing and an excess of 5' cryptic splicing events. Alternative splicing mediated by mutant U1 snRNA inactivates tumour-suppressor genes (PTCH1) and activates oncogenes (GLI2 and CCND2), and represents a target for therapy. These U1 snRNA mutations provide an example of highly recurrent and tissue-specific mutations of a non-protein-coding gene in cancer.

Influence of Oncotherapy and Clinical Parameters on Survival of Glioblastoma Patients: A Single Center Experience.

BACKGROUND: Routine administration of temozolomide (TMZ) in the treatment protocol of glioblastoma in the last few years resulted in improving survival parameters of these patients but efficacy of supplementary bevacizumab (BVC) monotherapy has not been evidently proven. In this study, the effectiveness of different postoperative therapy for glioblastoma patients treated in our institute was evaluated. In addition, the prognostic value of clinical parameters on survival was also analyzed. METHODS: Accordance of clinical parameters (age, gender, tumor localization, size, side, Karnofsky performance score, and extension of tumor removal), postoperative treatment (radiotherapy [RT], RT + TMZ, RT + TMZ + BVC), and survival data were tested by 104 patients operated on glioblastoma in the Department of Neurosurgery, University of Debrecen between 2002 and 2012. RESULTS: Concurrent chemo-RT resulted in significant longer overall survival (OS) than RT alone (PRTvs.RT + TMZ = 0.0219) and BVC treatment after progression during TMZ also elongated survival significantly (PRT vs. RT + TMZ + BVC < 0.0001; PRT + TMZvs.RT + TMZ + BVC = 0.0022), respectively. Clinical parameters showed no significant influence on OS in comparison with different methods of postoperative oncotherapy. CONCLUSIONS: Both TMZ and BVC had a beneficial effect on glioblastoma patients' survival, but tested clinical parameters showed no evident accordance with final outcome. Although neurosurgery has an indispensable role in resecting space occupying tumors and providing good postoperative performance score patients for oncotherapy, the survival of glioblastoma patients depends rather on radio- and chemo-sensitivity than tested clinical parameters.

Surgical treatment of tethered cord syndrome-comparing the results of surgeries with and without electrophysiological monitoring.

PURPOSE: To compare the short- and long-term outcomes after surgical treatment of tethered cord syndrome with and without electrophysiological monitoring. METHOD: We collected the preoperative data of 102 tethered cord surgeries of 91 patients. We compared the outcomes regarding the presence of intraoperative electrophysiology, the types of surgeries and the preoperative neurological condition. We also analysed the long-term outcomes in the cases of 69 patients. RESULTS: We found that intraoperative electrophysiology can reduce the perioperative surgical risk significantly (from 9.4 to 2.9%, p < 0.001), and electrophysiology is also beneficial in avoiding long-term progression in 88.7% (p = 0.03341). CONCLUSION: Tethered cord surgeries are safe and effective. With the use of intraoperative electrophysiology, the risk of postoperative worsening is as low as 2.9%, and long-term progression can be avoided in the majority of the patients.

Significance of liquid biopsy in glioblastoma - A review.

Glioblastoma (GBM) is the most common and most aggressive primary malignant brain tumor with a 16-24 -months overall survival time (OS). Effective management is hindered by intratumoral heterogeneity, a characteristic trait of GBM which results in subpopulations of cells with altered therapeutic responsiveness, different invasiveness and growth potential. Correct initial molecular profiling of the tumor, as well as following its molecular biological changes are further impeded by the intracranial location of the tumors, hence the risks of surgical interventions. Radiological examination, the sole non-invasive method of obtaining information about the tumors, also has limitations. This review article aims to summarize the currently available information about the promising applicability of liquid biopsy, extracellular vesicles (EVs), and circulating cell-free nucleic acids (cf-NAs) in GBM patients. Liquid biopsy is a quick and inexpensive way of obtaining exceptionally relevant information about tumors, and can be performed multiple times during the clinical course of the disease. Furthermore, integrating analyses of EVs and related cf-NAs in clinical practice might also help to establish diagnosis in a non-invasive manner, and complex oncotherapy could be indicated in the future without high-risk neurosurgical interventions.

Extracellular matrix differences in glioblastoma patients with different prognoses.

Glioblastoma is the most common malignant central nervous system tumor. Patient outcome remains poor despite the development of therapy and increased understanding of the disease in the past decades. Glioma cells invade the peritumoral brain, which results in inevitable tumor recurrence. Previous studies have demonstrated that the extracellular matrix (ECM) is altered in gliomas and serves a major role in glioma invasion. The present study focuses on differences in the ECM composition of tumors in patients with poor and improved prognosis. The mRNA and protein expression of 16 invasion-associated ECM molecules was determined using reverse trascription-quantitiative polymerase chain reaction and immunohistochemistry, respectively. Clinical factors of patients with different prognoses was also analyzed. It was determined that age and postoperative Karnofsky performance score were associated with patient survival. Furthermore, Fms-related tyrosine kinase 4/vascular endothelial growth factor receptor 3 (FLT4/VEGFR3), murine double minute 2 (MDM2) and matrix metallopeptidase 2 (MMP2) mRNA levels were significantly different between the two prognostic groups. Additionally, brevican, cluster of differentiation 44, hyaluronan mediated motility receptor, integrin-αV and -ß1, and MDM2 protein expression were indicated to be significantly different in immunohistochemistry slides. Using the expression profile, including the invasion spectrum of the samples, it was possible to identify the prognostic group of the sample with high efficacy, particularly in cases with poor prognosis. In conclusion, it was determined that ECM components exhibit different expression levels in tumors with different prognoses and thus the invasion spectrum can be used as a prognostic factor in glioblastoma.

Light Control of Salt-Induced Proline Accumulation Is Mediated by ELONGATED HYPOCOTYL 5 in Arabidopsis.

Plants have to adapt their metabolism to constantly changing environmental conditions, among which the availability of light and water is crucial in determining growth and development. Proline accumulation is one of the sensitive metabolic responses to extreme conditions; it is triggered by salinity or drought and is regulated by light. Here we show that red and blue but not far-red light is essential for salt-induced proline accumulation, upregulation of Δ1-PYRROLINE-5-CARBOXYLATE SYNTHASE 1 (P5CS1) and downregulation of PROLINE DEHYDROGENASE 1 (PDH1) genes, which control proline biosynthetic and catabolic pathways, respectively. Chromatin immunoprecipitation and electrophoretic mobility shift assays demonstrated that the transcription factor ELONGATED HYPOCOTYL 5 (HY5) binds to G-box and C-box elements of P5CS1 and a C-box motif of PDH1. Salt-induced proline accumulation and P5CS1 expression were reduced in the hy5hyh double mutant, suggesting that HY5 promotes proline biosynthesis through connecting light and stress signals. Our results improve our understanding on interactions between stress and light signals, confirming HY5 as a key regulator in proline metabolism.

The Expressional Pattern of Invasion-Related Extracellular Matrix Molecules in CNS Tumors.

Aim of the study: Astrocytomas are primary CNS malignancies which infiltrate the peritumoral tissue, even when they are low-grade. Schwannomas are also primary CNS tumors, however, they do not show peritumoral infiltration similarly to brain metastases which almost never invade the neighboring parts of brain. Extracellular matrix is altered in composition in various cancer types and is proposed to play an important role in the development of invasiveness of astrocytic tumors. This study aims to identify differences in the ECM composition of CNS tumors with different invasiveness.Materials and methods: The mRNA and protein levels of ECM components were measured by QRT-PCR and mass-spectrometry, respectively, in grade II astrocytoma, NSCLC brain metastasis, schwannomas, and non-tumor brain control samples. Expressional data was analyzed statistically with ANOVA and nearest neighbor search.Results: There is a significant difference in the expressional pattern of invasion-related ECM components among various CNS tumors, especially among those of different embryonic origin. Non-invasive tumors show only slight differences in the expressional pattern of ECM molecules. Tumor samples can be separated based on their expressional pattern using statistical classifiers, therefore the ECM composition seems to be typical of various cancer types.Conclusions: Differences in the expressional pattern of the ECM could be responsible for the different invasiveness of various CNS tumors.