Enhancement of S-nitrosylation in glycosylated hemoglobin

In this study, we report a novel differential nitric oxide interaction with nonglycosylated and glycosylated hemoglobin. After in vitro incubation of hemoglobin with S-nitroso N-acetyl penicillamine (SNAP), S-nitrosoglutathione, or S-nitrosocysteine, S-nitrosylation was significantly higher in human glycosylated hemoglobin purified from diabetic subjects compared to nondiabetic controls. Inversely, spontaneous decomposition was significantly lower for S-nitrosohemoglobin obtained from glycosylated hemoglobin. Bidimensional isoelectric focusing of hemoglobins incubated in vitro with SNAP also revealed a greater interaction of nitric oxide with glycosylated hemoglobin. In addition, a significantly higher level of S-nitrosohemoglobin was found in erythrocyte lysates from streptozotocin-induced diabetic rats compared to control rats. We suggest that highly glycosylated hemoglobin in diabetic subjects may favor S-nitrosylation, which may in turn impair vascular function, and participate in diabetic microangiopathy.     

Comparative Network Analysis of Preterm vs. Full-Term Infant-Mother Interactions

Several studies have reported that interactions of mothers with preterm infants show differential characteristics compared to that of mothers with full-term infants. Interaction of preterm dyads is often reported as less harmonious. However, observations and explanations concerning the underlying mechanisms are inconsistent. In this work 30 preterm and 42 full-term mother-infant dyads were observed at one year of age. Free play interactions were videotaped and coded using a micro-analytic coding system. The video records were coded at one second resolution and studied by a novel approach using network analysis tools. The advantage of our approach is that it reveals the patterns of behavioral transitions in the interactions. We found that the most frequent behavioral transitions are the same in the two groups. However, we have identified several high and lower frequency transitions which occur significantly more often in the preterm or full-term group. Our analysis also suggests that the variability of behavioral transitions is significantly higher in the preterm group. This higher variability is mostly resulted from the diversity of transitions involving non-harmonious behaviors. We have identified a maladaptive pattern in the maternal behavior in the preterm group, involving intrusiveness and disengagement. Application of the approach reported in this paper to longitudinal data could elucidate whether these maladaptive maternal behavioral changes place the infant at risk for later emotional, cognitive and behavioral disturbance.     

Relation of Raman order parameters to spin labeling parameters

For the quantitation of Raman and spin labeling data order parameters are commonly used. The spin label order parameter measured at any depth in the layer is a weighed sum of the segmental order since, due to fast conformational interconversions, each CH₂ segment is partly in trans and partly in non-trans, e.g. gauche, kink, jog, etc., conformation during the measurement. The weighing factor, the trans finding probability, varies along the chain (cf. flexibility profile) but its mean value should be equal to the Raman trans order parameter. This correlation is illustrated with the experimental data obtained for dipalmitoyl phosphatidylcholine and n-alcohol mixtures. The rate of rotational diffusion, a dynamical parameter from spin labeling studies, is correlated with the lateral packing density as measured by the Raman lateral order parameter. For the obtained linear correlation a qualitative explanation is given.The effect of a series of long chain alcohols on the phase transition characteristics of dipalmitoyl phosphatidylcholine was investigated. The possible role of hydrogen bonding in the interfacial region is emphasized.     

Mammalian Target of Rapamycin (mTOR) Activity Dependent Phospho-Protein Expression in Childhood Acute Lymphoblastic Leukemia (ALL)

Modern treatment strategies have improved the prognosis of childhood ALL; however, treatment still fails in 25–30% of patients. Further improvement of treatment may depend on the development of targeted therapies. mTOR kinase, a central mediator of several signaling pathways, has recently attracted remarkable attention as a potential target in pediatric ALL. However, limited data exists about the activity of mTOR. In the present study, the amount of mTOR activity dependent phospho-proteins was characterized by ELISA in human leukemia cell lines and in lymphoblasts from childhood ALL patients (n = 49). Expression was measured before and during chemotherapy and at relapses. Leukemia cell lines exhibited increased mTOR activity, indicated by phospho-S6 ribosomal protein (p-S6) and phosphorylated eukaryotic initiation factor 4E binding protein (p-4EBP1). Elevated p-4EBP1 protein levels were detected in ALL samples at diagnosis; efficacy of chemotherapy was followed by the decrease of mTOR activity dependent protein phosphorylation. Optical density (OD) for p-4EBP1 (ELISA) was significantly higher in patients with poor prognosis at diagnosis, and in the samples of relapsed patients. Our results suggest that measuring mTOR activity related phospho-proteins such as p-4EBP1 by ELISA may help to identify patients with poor prognosis before treatment, and to detect early relapses. Determining mTOR activity in leukemic cells may also be a useful tool for selecting patients who may benefit from future mTOR inhibitor treatments.     

The Expression of Psoriasin (S100A7) and CD24 Is Linked and Related to the Differentiation of Mammary Epithelial Cells

Psoriasin (S100A7), a member of the S100 family of calcium-binding proteins, is highly expressed in high-grade ductal carcinoma in situ (DCIS) and in the benign hyperproliferative skin disorder psoriasis. The gene that encodes psoriasin and many other S100 genes are located within a gene cluster on chromosome region 1q21, known as the epidermal differentiation complex. This cluster contains genes for several differentiation markers that play important roles in the terminal differentiation of the epidermis. The purpose of the present study was to evaluate the role of psoriasin in the differentiation process of mammary epithelial cells. Normal mammary epithelial cells (MCF10A) cultured in confluence and suspension, conditions known to induce psoriasin expression, demonstrated a shift towards a more differentiated phenotype indicated by an increase in the expression of the luminal differentiation markers CD24 and MUC1 and the reduced expression of the breast stem cell marker CD44. The expression of psoriasin and MUC1 was most pronounced in the CD24⁺-enriched fraction of confluent MCF10A cells. The shift towards a more differentiated phenotype was abolished upon the downregulation of psoriasin using short hairpin RNA (shRNA) and small interfering RNA (siRNA). Using specific inhibitors, we showed that psoriasin and CD24 expression was regulated by reactive oxygen species (ROS) and the nuclear factor (NF)-κB signaling pathways. While immunohistochemical analyses of DCIS showed heterogeneity, the expression of psoriasin and CD24 showed a similar staining pattern. Our findings suggest that the expression of psoriasin is linked to the luminal differentiation marker CD24 in mammary epithelial cells. Psoriasin demonstrated an essential role in the shift towards a more differentiated CD24⁺ phenotype, supporting the hypothesis that psoriasin plays a role in the differentiation of luminal mammary epithelial cells.     

Morphine-like analgesic effect of a pituitary hormone, β-lipotropin

The analgesic effect f β-lipotropin /β -LPH/ and its fragments administered intracerebroventricularly /ICV/ to rats was studied. β -LPH proved to be a specific, morphine-like analgesic possesing 2.2 times weaker analgesic potency than morphine, calculated on molar base. Tryptic digest of β -LPH or smaller fragments of the hormone /LPH-/61 2 65/-eptide and LPH-/61–69/-peptide/ were devoid of significant analgesic activity. The in vivo results appeared to be in contrast to those previously obtained in longitudinal muscle strip of guinea-pig ileum, in vitro. A tentative explanation of this apparent contradiction is also given.     

Lost in the City: Revisiting Milgram's Experiment in the Age of Social Networks

As more and more users access social network services from smart devices with GPS receivers, the available amount of geo-tagged information makes repeating classical experiments possible on global scales and with unprecedented precision. Inspired by the original experiments of Milgram, we simulated message routing within a representative sub-graph of the network of Twitter users with about 6 million geo-located nodes and 122 million edges. We picked pairs of users from two distant metropolitan areas and tried to find a route between them using local geographic information only; our method was to forward messages to a friend living closest to the target. We found that the examined network is navigable on large scales, but navigability breaks down at the city scale and the network becomes unnavigable on intra-city distances. This means that messages usually arrived to the close proximity of the target in only 3–6 steps, but only in about 20% of the cases was it possible to find a route all the way to the recipient, in spite of the network being connected. This phenomenon is supported by the distribution of link lengths; on larger scales the distribution behaves approximately as , which was found earlier by Kleinberg to allow efficient navigation, while on smaller scales, a fractal structure becomes apparent. The intra-city correlation dimension of the network was found to be , less than the dimension of the distribution of the population.