Protein-associated O-GIcNAc, a multifunctional mechanism in cell signaling and its role in the pathogenesis of diabetes, stress and malignant diseases

Sve veći broj dokaza ukazuje na to da put biosinteze heksozamina (HPB, engl. hexosamine biosynthesispathway) ima značajnu ulogu u modulaciji unutarstaničnih putova preoblikovanja signala. Njegov krajnji produkt, tj. UDP-GlcNAc, je supstrat kod spajanja O-vezanog β-N-acetilglukozamina (O-GlcNAc) s ostatcima Ser/Thr. To spajanje regulira široki raspon proteina preko interferencije s fosforilacijom. O-GlcNAc je dinamična posttranslacijska modifikacija koja je bitna za funkciju normalne stanice u sisavaca; njeno je, međutim, najveće značenje utvrđeno u patološkim procesima. Kako HBP iziskuje glukozu, veliki unos glukoze znatno povećava protok kroz HBP te također povećava omjer proteina povezanih s O-GlcNac. To, pak, utječe na različite funkcije stanice koje uključuju tradicijski prihvaćene štetne učinke u šećernoj bolesti i njenim komplikacijama ili, kao što je nedavno nađeno, O-GlcNAc bi mogao biti koristan kod ishemijskih/reperfuzijskih ozljeda. U ovom pregledu sažeto prikazujemo trenutne spoznaje u istraživanju O-GlcNAc vezane za njegovo sudjelovanje u signalnim putovima i staničnim procesima. Također se usredotočujemo na utjecaj O-GlcNAc u bolestima kao što su šećerna bolest, upala, razvoj zloćudnih bolesti ili ozljede uzrokovane hipoksijom.Growing evidence suggests that hexosamine biosynthesis pathway (HBP) plays a significant role in the modulation of intracellular signaling transduc-tion pathways. Its end product, UDP-GlcNAc is a substrate for the addition of O-linked β-N-acetylglucosamine (O-GlcNAc) to Ser/Thr residues. This process regulates a wide range of proteins usually by interfering with phosphoryla-tion. O-GlcNAc is a dynamic posttranslational modification, which is essential in normal mammalian cellular function; however, its main significance has been revealed in pathological processes. Since HBP requires glucose, high glucose intake considerably increases the flux through HBP and also increases the ratio of O-GlcNAc-associated proteins. This has an impact on various cellular functions, involving either the traditionally recognized detrimental effects in diabetes and diabetic complications or, as found recently, O-GlcNAc might be beneficial in ischemia/reperfusion injuries. In this review we summarize the current findings in O-GlcNAc research concerning its participation in signaling pathways and cellular processes. We also focus on the impact of O-GlcNAc in diseases such as diabetes, inflammation, development of malignancies or hypoxia-induced injuries

Effect of drought on yield components of maize hybrids (Zea mays L)

When investigating drought tolerance, it must not be forgotten that drought stress is a complex phenomenon ex¬hibiting quite different characters in different years and locations. For this reason, the plant response to drought is also a complex process. In our study, 83 maize hybrids originating from various countries were investigated over a period of two years, under irrigated and non-irrigated conditions. The drought tolerance of plants in the non-irrigated plots was analysed in terms of flowering synchrony and yield components. It could be concluded from the results that in response to long-term water deficit the period between tasselling and silking became longer, while the analysis of yield components revealed the greatest reductions in the number of kernels per ear and in the proportion of seed set. As the degree of proterandry increased, there was a decline in the grain yield, confirming that the analysis of this trait could be a way of predicting drought tolerance. Considerable differences in drought tolerance were observed between the genetic materials included in the analysis, suggesting the presence among these parental lines and hybrids of genotypes resistant to long-term water deficit, suitable for cultivation under dry conditions. An analysis of correlations between the traits revealed that proterandry should be treated as a priority trait when investigating drought stress tolerance, as better predictions can be made of both drought tolerance and potential yields, leading to more reliable selection for higher yields

Helium in the polar wind

The coupled, time-dependent continuity, momentum and energy equations for four charged species (H+, He+, O+ and electrons) moving through a stationary upper neutral atmosphere (composed of O2, N2, O, He, H) were solved along open geomagnetic field lines using a modified version of the /5/ model. The thermospheric densities and temperatures, obtained from the MSIS-86 model /7/, were used to calculate neutral-ion sources, sinks, and collision frequencies. The various cross sections and conductivities employed by the /5/ model were also updated. The paper presents the first time-dependent solutions for the He+ component of the polar wind. Special attention is paid to the solar cycle variation of the ion upflows.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30319/1/0000721.pd

3D global multi‐species Hall‐MHD simulation of the Cassini T9 flyby

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94961/1/grl23831.pd

Two‐species, 3D, MHD simulation of Europa's interaction with Jupiter's magnetosphere

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95391/1/grl12120.pd

3D multi‐fluid MHD studies of the solar wind interaction with Mars

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95115/1/grl13388.pd

High-resolution DNA copy number and gene expression analyses distinguish chromophobe renal cell carcinomas and renal oncocytomas

Contains fulltext : 80487.pdf (publisher's version ) (Open Access)BACKGROUND: The diagnosis of benign renal oncocytomas (RO) and chromophobe renal cell carcinomas (RCC) based on their morphology remains uncertain in several cases. METHODS: We have applied Affymetrix GeneChip Mapping 250 K NspI high-density oligoarrays to identify small genomic alterations, which may occur beyond the specific losses of entire chromosomes, and also Affymetrix GeneChip HG-U133 Plus2.0 oligoarrays for gene expression profiling. RESULTS: By analysing of DNA extracted from 30 chRCCs and 42 ROs, we have confirmed the high specificity of monosomies of chromosomes 1, 2, 6, 10, 13, 17 and 21 in 70-93% of the chRCCs, while ROs displayed loss of chromosome 1 and 14 in 24% and 5% of the cases, respectively. We demonstrated that chromosomal gene expression biases might correlate with chromosomal abnormalities found in chromophobe RCCs and ROs. The vast majority genes downregulated in chromophobe RCC were mapped to chromosomes 2, 6, 10, 13 and 17. However, most of the genes overexpressed in chromophobe RCCs were located to chromosomes without any copy number changes indicating a transcriptional regulation as a main event. CONCLUSION: The SNP-array analysis failed to detect recurrent small deletions, which may mark loci of genes involved in the tumor development. However, we have identified loss of chromosome 2, 10, 13, 17 and 21 as discriminating alteration between chromophobe RCCs and ROs. Therefore, detection of these chromosomal changes can be used for the accurate diagnosis in routine histology

Identification of Behaviour in Freely Moving Dogs (Canis familiaris) Using Inertial Sensors

Monitoring and describing the physical movements and body postures of animals is one of the most fundamental tasks of ethology. The more precise the observations are the more sophisticated the interpretations can be about the biology of a certain individual or species. Animal-borne data loggers have recently contributed much to the collection of motion-data from individuals, however, the problem of translating these measurements to distinct behavioural categories to create an ethogram is not overcome yet. The objective of the present study was to develop a “behaviour tracker”: a system composed of a multiple sensor data-logger device (with a tri-axial accelerometer and a tri-axial gyroscope) and a supervised learning algorithm as means of automated identification of the behaviour of freely moving dogs. We collected parallel sensor measurements and video recordings of each of our subjects (Belgian Malinois, N=12; Labrador Retrievers, N=12) that were guided through a predetermined series of standard activities. Seven behavioural categories (lay, sit, stand, walk, trot, gallop, canter) were pre-defined and each video recording was tagged accordingly. Evaluation of the measurements was performed by support vector machine (SVM) classification. During the analysis we used different combinations of independent measurements for training and validation (belonging to the same or different individuals or using different training data size) to determine the robustness of the application. We reached an overall accuracy of above 90% perfect identification of all the defined seven categories of behaviour when both training and validation data belonged to the same individual, and over 80% perfect recognition rate using a generalized training data set of multiple subjects. Our results indicate that the present method provides a good model for an easily applicable, fast, automatic behaviour classification system that can be trained with arbitrary motion patterns and potentially be applied to a wide range of species and situations

High-Density Real-Time PCR-Based in Vivo Toxicogenomic Screen to Predict Organ-Specific Toxicity

Toxicogenomics, based on the temporal effects of drugs on gene expression, is able to predict toxic effects earlier than traditional technologies by analyzing changes in genomic biomarkers that could precede subsequent protein translation and initiation of histological organ damage. In the present study our objective was to extend in vivo toxicogenomic screening from analyzing one or a few tissues to multiple organs, including heart, kidney, brain, liver and spleen. Nanocapillary quantitative real-time PCR (QRT-PCR) was used in the study, due to its higher throughput, sensitivity and reproducibility, and larger dynamic range compared to DNA microarray technologies. Based on previous data, 56 gene markers were selected coding for proteins with different functions, such as proteins for acute phase response, inflammation, oxidative stress, metabolic processes, heat-shock response, cell cycle/apoptosis regulation and enzymes which are involved in detoxification. Some of the marker genes are specific to certain organs, and some of them are general indicators of toxicity in multiple organs. Utility of the nanocapillary QRT-PCR platform was demonstrated by screening different references, as well as discovery of drug-like compounds for their gene expression profiles in different organs of treated mice in an acute experiment. For each compound, 896 QRT-PCR were done: four organs were used from each of the treated four animals to monitor the relative expression of 56 genes. Based on expression data of the discovery gene set of toxicology biomarkers the cardio- and nephrotoxicity of doxorubicin and sulfasalazin, the hepato- and nephrotoxicity of rotenone, dihydrocoumarin and aniline, and the liver toxicity of 2,4-diaminotoluene could be confirmed. The acute heart and kidney toxicity of the active metabolite SN-38 from its less toxic prodrug, irinotecan could be differentiated, and two novel gene markers for hormone replacement therapy were identified, namely fabp4 and pparg, which were down-regulated by estradiol treatment

The effectiveness of a clinically integrated e-learning course in evidence-based medicine: A cluster randomised controlled trial

BACKGROUND: To evaluate the educational effects of a clinically integrated e-learning course for teaching basic evidence-based medicine (EBM) among postgraduates compared to a traditional lecture-based course of equivalent content. METHODS: We conducted a cluster randomised controlled trial in the Netherlands and the UK involving postgraduate trainees in six obstetrics and gynaecology departments. Outcomes (knowledge gain and change in attitude towards EBM) were compared between the clinically integrated e-learning course (intervention) and the traditional lecture based course (control). We measured change from pre- to post-intervention scores using a validated questionnaire assessing knowledge (primary outcome) and attitudes (secondary outcome). RESULTS: There were six clusters involving teaching of 61 postgraduate trainees (28 in the intervention and 33 in the control group). The intervention group achieved slightly higher scores for knowledge gain compared to the control, but these results were not statistically significant (difference in knowledge gain: 3.5 points, 95% CI -2.7 to 9.8, p = 0.27). The attitudinal changes were similar for both groups. CONCLUSION: A clinically integrated e-learning course was at least as effective as a traditional lecture based course and was well accepted. Being less costly than traditional teaching and allowing for more independent learning through materials that can be easily updated, there is a place for incorporating e-learning into postgraduate EBM curricula that offer on-the-job training for just-in-time learning. TRIAL REGISTRATION: Trial registration number: ACTRN12609000022268