Intra-brain microinjection of human mesenchymal stem cells decreases allodynia in neuropathic mice

Neuropathic pain is a very complex disease, involving several molecular pathways. Current available drugs are usually not acting on the several mechanisms underlying the generation and propagation of pain. We used spared nerve injury model of neuropathic pain to assess the possible use of human mesenchymal stem cells (hMSCs) as anti-neuropathic tool. Human MSCs were transplanted in the mouse lateral cerebral ventricle. Stem cells injection was performed 4 days after sciatic nerve surgery. Neuropathic mice were monitored 7, 10, 14, 17, and 21 days after surgery. hMSCs were able to reduce pain-like behaviors, such as mechanical allodynia and thermal hyperalgesia, once transplanted in cerebral ventricle. Anti-nociceptive effect was detectable from day 10 after surgery (6 days post cell injection). Human MSCs reduced the mRNA levels of the pro-inflammatory interleukin IL-1β mouse gene, as well as the neural β-galactosidase over-activation in prefrontal cortex of SNI mice. Transplanted hMSCs were able to reduce astrocytic and microglial cell activation.     

Central neural control of pineal melatonin synthesis in the rat

To investigate a possible central neural influence on nocturnal pineal metabolic activity in rats, frontal transsections of the stria medullaris thalami were conducted. Enzymes involved in melatonin synthesis, i.e. N-acetyltransferase and hydroxyindole-O-methyl-transferase, exhibited reduced activities in operated animals when compared to controls. These results indicate a modulatory role of central structures on nocturnal pineal indole metabolism.     

深亚微米纤锌矿相AlGaN/GaN MODFET输出特性的微分负阻效应

用全带组合Monte Carlo方法模拟了Al_0.15Ga_0.85N/GaN MODFET 的直流特性. 模拟器件的栅极长度L_g为0.2 μm, 沟道长度LDS为0.4 mm. 在模拟得到的I_DS-V_DS输出特性曲线中, 发现了微分负阻效应, 即V_GS为固定值时, 当V_DS逐渐增加, 并达到某一阈值时, I_DS会随着VDS的增大而减小. 对GaN体材料的速度-电场特性和对器件的二维电子气沟道内的电场和速度分布的分析表明, 沟道内电子平均漂移速度的负阻效应导致了输出特性的微分负阻效应, 二维电子气沟道内的瞬态输运对微分负阻特性也有一定影响. 这种效应只有在超短沟道MODFET中才能发生.     

Riemanns Einfluß auf E. Betti und F. Casorati

Ohne Zusammenfassung Vorgelegt von A. P. Youschkevitch     

Local sleep in awake rats

In an awake state, neurons in the cerebral cortex fire irregularly and electroencephalogram (EEG) recordings display low-amplitude, high-frequency fluctuations. During sleep, neurons oscillate between 'on' periods, when they fire as in an awake brain, and 'off' periods, when they stop firing altogether and the EEG displays high-amplitude slow waves. However, what happens to neuronal firing after a long period of being awake is not known. Here we show that in freely behaving rats after a long period in an awake state, cortical neurons can go briefly 'offline' as in sleep, accompanied by slow waves in the local EEG. Neurons often go offline in one cortical area but not in another, and during these periods of 'local sleep', the incidence of which increases with the duration of the awake state, rats are active and display an 'awake' EEG. However, they are progressively impaired in a sugar pellet reaching task. Thus, although both the EEG and behaviour indicate wakefulness, local populations of neurons in the cortex may be falling asleep, with negative consequences for performance.     

Le funzioni a periodi multipli nella corrispondenza tra Hermite e Casorati

Presentato da C. Truesdell     

Central neural control of pineal melatonin synthesis in rat

Summary To investigate a possible central neural influence on nocturnal pineal metabolic activity, frontal transsections of the stria medullaris thalami were conducted. Enzymes involved in melatonin synthesis, i.e. N-acetyltransferase and hydroxyindole-O-methyl-transferase, exhibited reduced activities in operated animals when compared to controls. These results indicate a modulatory role of central structures on noctural pineal indole metabolism.This study was supported by the Deutsche Forschungsgemeischaft and the Stifung Volkswagenwerk. The technical assistance provided by M. Henschel, I. v. Graevenitz and G. Schlich is gratefuly acknowledged.     

Selection of the relevant information set for predictive relationships analysis between time series

In time series analysis, a vector Y is often called causal for another vector X if the former helps to improve the k‐step‐ahead forecast of the latter. If this holds for k=1, vector Y is commonly called Granger‐causal for X . It has been shown in several studies that the finding of causality between two (vectors of) variables is not robust to changes of the information set. In this paper, using the concept of Hilbert spaces, we derive a condition under which the predictive relationships between two vectors are invariant to the selection of a bivariate or trivariate framework. In more detail, we provide a condition under which the finding of causality (improved predictability at forecast horizon 1) respectively non‐causality of Y for X is unaffected if the information set is either enlarged or reduced by the information in a third vector Z . This result has a practical usefulness since it provides a guidance to validate the choice of the bivariate system { X , Y } in place of { X , Y , Z }. In fact, to test the ‘goodness’ of { X , Y } we should test whether Z Granger cause X not requiring the joint analysis of all variables in { X , Y , Z }. Copyright © 2002 John Wiley & Sons, Ltd.     

Silencing of RB1 but not of RB2/P130 induces cellular senescence and impairs the differentiation potential of human mesenchymal stem cells

Stem cell senescence is considered deleterious because it may impair tissue renewal and function. On the other hand, senescence may arrest the uncontrolled growth of transformed stem cells and protect organisms from cancer. This double function of senescence is strictly linked to the activity of genes that the control cell cycle such as the retinoblastoma proteins RB1, RB2/P130, and P107. We took advantage of the RNA interference technique to analyze the role of these proteins in the biology of mesenchymal stem cells (MSC). Cells lacking RB1 were prone to DNA damage. They showed elevated levels of p53 and p21^cip1 and increased regulation of RB2/P130 and P107 expression. These cells gradually adopted a senescent phenotype with impairment of self-renewal properties. No significant modification of cell growth was observed as it occurs in other cell types or systems. In cells with silenced RB2/P130, we detected a reduction of DNA damage along with a higher proliferation rate, an increase in clonogenic ability, and the diminution of apoptosis and senescence. Cells with silenced RB2/P130 were cultivated for extended periods of time without adopting a transformed phenotype. Of note, acute lowering of P107 did not induce relevant changes in the in vitro behavior of MSC. We also analyzed cell commitment and the osteo-chondro-adipogenic differentiation process of clones derived by MSC cultures. In all clones obtained from cells with silenced retinoblastoma genes, we observed a reduction in the ability to differentiate compared with the control clones. In summary, our data show evidence that the silencing of the expression of RB1 or RB2/P130 is not compensated by other gene family members, and this profoundly affects MSC functions.     

Biased binding of class IA phosphatidyl inositol 3-kinase subunits to inducible costimulator (CD278)

To better understand T lymphocyte costimulation by inducible costimulator (ICOS; H4; CD278), we analyzed proteins binding to ICOS peptides phosphorylated at the Y₁₉₁MFM motif. Phosphorylated ICOS binds class IA phosphatidyl inositol 3-kinase (PI3-K) p85α, p50-55α and p85β regulatory subunits and p110α, p110δ and p110β catalytic subunits. Intriguingly, T cells expressed high levels of both p110α or p110δ catalytic subunits, yet ICOS peptides, cell surface ICOS or PI3-kinase class IA regulatory subunits preferentially coprecipitated p110α catalytic subunits. Silencing p110α or p110δ partially inhibited Akt/PKB activation induced by anti-CD3 plus anti-ICOS antibodies. However, silencing p110α enhanced and silencing p110δ inhibited Erk activation. Both p110α- and p110δ-specific inhibitors blocked cytokine secretion induced by TCR/CD3 activation with or without ICOS costimulus, but only p110α inhibitors blocked ICOS-induced cell elongation. Thus, p110α and p110δ are essential to optimal T cell activation, but their abundance and activity differentially tune up distinct ICOS signaling pathways.