Modeled changes of cerebellar activity in mutant mice are predictive of their learning impairments

Translating neuronal activity to measurable behavioral changes has been a long-standing goal of systems neuroscience. Recently, we have developed a model of phase-reversal learning of the vestibulo-ocular reflex, a well-established, cerebellar-dependent task. The model, comprising both the cerebellar cortex and vestibular nuclei, reproduces behavioral data and accounts for the changes in neural activity during learning in wild type mice. Here, we used our model to predict Purkinje cell spiking as well as behavior before and after learning of five different lines of mutant mice with distinct cell-specific alterations of the cerebellar cortical circuitry. We tested these predictions by obtaining electrophysiological data depicting changes in neuronal spiking. We show that our data is largely consistent with the model predictions for simple spike modulation of Purkinje cells and concomitant behavioral learning in four of the mutants. In addition, our model accurately predicts a shift in simple spike activity in a mutant mouse with a brainstem specific mutation. This combination of electrophysiological and computational techniques opens a possibility of predicting behavioral impairments from neural activity

Differential effects of selective inhibitors targeting the PI3K/AKT/mTOR pathway in acute lymphoblastic leukemia

Purpose: Aberrant PI3K/AKT/mTOR signaling has been linked to oncogenesis and therapy resistance in various malignancies including leukemias. In Philadelphia chromosome (Ph) positive leukemias, activation of PI3K by dysregulated BCR-ABL tyrosine kinase (TK) contributes to the pathogenesis and development of resistance to ABL-TK inhibitors (TKI). The PI3K pathway thus is an attractive therapeutic target in BCR-ABL positive leukemias, but its role in BCR-ABL negative ALL is conjectural. Moreover, the functional contribution of individual components of the PI3K pathway in ALL has not been established. Experimental design: We compared the activity of the ATP-competitive pan-PI3K inhibitor NVP-BKM120, the allosteric mTORC1 inhibitor RAD001, the ATP-competitive dual PI3K/mTORC1/C2 inhibitors NVP-BEZ235 and NVP-BGT226 and the combined mTORC1 and mTORC2 inhibitors Torin 1, PP242 and KU-0063794 using long-term cultures of ALL cells (ALL-LTC) from patients with B-precursor ALL that expressed the BCR-ABL or TEL-ABL oncoproteins or were BCR-ABL negative. Results: Dual PI3K/mTOR inhibitors profoundly inhibited growth and survival of ALL cells irrespective of their genetic subtype and their responsiveness to ABL-TKI. Combined suppression of PI3K, mTORC1 and mTORC2 displayed greater antileukemic activity than selective inhibitors of PI3K, mTORC1 or mTORC1 and mTORC2. Conclusions: Inhibition of the PI3K/mTOR pathway is a promising therapeutic approach in patients with ALL. Greater antileukemic activity of dual PI3K/mTORC1/C2 inhibitors appears to be due to the redundant function of PI3K and mTOR. Clinical trials examining dual PI3K/mTORC1/C2 inhibitors in patients with B-precursor ALL are warranted, and should not be restricted to particular genetic subtypes

Differences in Iron Removal from Carbon Nanoonions and Multiwall Carbon Nanotubes for Analytical Purpose

The paper describes the differences between wet iron removal from carbon nanoonions and from multiwall carbon nanotubes for analytical purpose. Nowadays, both carbon nanoonions and multiwall carbon nanotubes are one of the most interesting materials with applicability in electronics, medicine and biotechnology. Medical applications of those nanomaterials require not only recognition of their structure but also measurement of metal impurities concentration. Inductively coupled plasma optical emission spectrometry as a method for Fe-determination requires liquid samples. Hence, we propose various protocols for leaching of iron from studied materials. Our results proved that structure of nanomaterials have an impact on the efficiency of iron removal

Can organized leisure-time activities buffer the negative outcomes of unstructured activities for adolescents' health?

We aimed to assess the associations of involvement in selected unstructured activities (UA) with health-risk behaviours and academic achievement and the degree to which the participation in organized leisure-time activities (OLTA) changes these associations. Using a sample of 6935 Czech adolescents aged 13 and 15 years, we investigated adolescents' weekly involvement in hanging out, visiting shopping malls for fun and meeting friends after 8 p.m., OLTA and engagement in three health-risk behaviours and academic achievement. Weekly involvement in the selected UA was associated with higher odds for regular smoking, being drunk, having early sexual intercourse and low academic achievement. Concurrent participation in OLTA did not buffer these negative outcomes, except for sexual experience. However, those highly engaged only in UA were more likely to participate in the health-risk behaviours and report worse academic achievement than those participating in any OLTA concurrently. The selected UA are strongly associated with an increased occurrence of adolescents' health-risk behaviours and low academic achievement. Concurrent participation in OLTA does not buffer these negative outcomes significantly, but adolescents engaged only in UA consistently report the least favourable outcomes

Light-Induced Defect Formation and Pt Single Atoms Synergistically Boost Photocatalytic H2 Production in 2D TiO2-Bronze Nanosheets ?

Ultrathin two-dimensional (2D) semiconductor nanosheets decorated with single atomic species (SAs) have recently attracted increasing attention due to their abundant surface-exposed reactive sites and maximum SAs binding capabilities thus lowering the catalyst cost, without sacrificing high performance for photocatalytic hydrogen (H2) production from water. Here, we present a strategy to prepare titanium dioxide-bronze nanosheets (TiO2-BNS) and H2-reduced TiO2 nanosheets (TiO2- HRNS) synthesized, characterized, and applied for photocatalytic H2 production. Surprisingly, black TiO2-HRNS show complete photo inactivity, while the TiO2-BNS-Pt0.05 nanohybrid shows excellent H2 production rate with a very low loading of 0.05 wt % Pt. TiO2-BNS-Pt0.05 presents around 10 and 99 times higher photocatalytic rate than pristine TiO2-BNS under solar and 365 nm UV-LED light irradiation, respectively. Due to the 2D morphology and the presence of abundant coordinating sites, the successful formation of widely dispersed Pt SAs was achieved. Most excitingly, the in situ formation of surface-exposed defect sites (Ti3+) was observed for TiO2-BNS under light illumination, suggesting their significant role in enhancing the H2 production rate. This self-activation and amplification behavior of TiO2-BNS can be extended to other 2D systems and applied to other photocatalytic reactions, thus providing a facile approach for fully utilizing noble metal catalysts via the successful formation of SAs

Differences in Iron Removal from Carbon Nanoonions and Multiwall Carbon Nanotubes for Analytical Purpose

The paper describes the differences between wet iron removal from carbon nanoonions and from multiwall carbon nanotubes for analytical purpose. Nowadays, both carbon nanoonions and multiwall carbon nanotubes are one of the most interesting materials with applicability in electronics, medicine and biotechnology. Medical applications of those nanomaterials require not only recognition of their structure but also measurement of metal impurities concentration. Inductively coupled plasma optical emission spectrometry as a method for Fe-determination requires liquid samples. Hence, we propose various protocols for leaching of iron from studied materials. Our results proved that structure of nanomaterials have an impact on the efficiency of iron removal

The HADES Tracking System

The tracking system of the dielectron spectrometer HADES at GSI Darmstadt is formed out of 24 low-mass, trapezoidal multi-layer drift chambers providing in total about 30 square meter of active area. Low multiple scattering in the in total four planes of drift chambers before and after the magnetic field is ensured by using helium-based gas mixtures and aluminum cathode and field wires. First in-beam performance results are contrasted with expectations from simulations. Emphasis is placed on the energy loss information, exploring its relevance regarding track recognition.Comment: 6 pages, 4 figures, presented at the 10th Vienna Conference on Instrumentation, Vienna, February 2004, to be published in NIM A (special issue

A cerebellar learning model that reproduces the behavior of vestibulo-ocular reflex adaptation in wild-type and knock-out mice

The cerebellum is crucial for different types of motor learning. Established theories of cerebellar learning posit that the cerebellum learns by adjusting the weights of Parallel Fiber (PF) to Purkinje cells (PC) synapses, thanks to teaching signals provided by Climbing Fiber inputs. While these theories are consistent with a large body of experimental data, in particular on synaptic plasticity in PF to PC synapses, they cannot easily explain a growing body of experimental work, which seems to indicate a significant role of other sites of plasticity. Recent advances in the development of a large number in transgenic animals, as well as behavioral and electrophysiogical comparative studies between these animals and wild-type animals, have opened an unprecedented window into the mechanisms underlying learning in this structure. In particular, it has been shown that specific knock-outs are impaired selectively on difficult variants of the vestibulo-ocular reflex (VOR) adaptation task, one of the most studied cerebellar-dependent motor learning tasks. These impairments can occur even though the classical plasticity mechanisms are left untouched. These data pose significant new challenges for established models of cerebellar learning

New Young Star Candidates in BRC 27 and BRC 34

We used archival Spitzer Space Telescope mid-infrared data to search for young stellar objects (YSOs) in the immediate vicinity of two bright-rimmed clouds, BRC 27 (part of CMa R1) and BRC 34 (part of the IC 1396 complex). These regions both appear to be actively forming young stars, perhaps triggered by the proximate OB stars. In BRC 27, we find clear infrared excesses around 22 of the 26 YSOs or YSO candidates identified in the literature, and identify 16 new YSO candidates that appear to have IR excesses. In BRC 34, the one literature-identified YSO has an IR excess, and we suggest 13 new YSO candidates in this region, including a new Class I object. Considering the entire ensemble, both BRCs are likely of comparable ages, within the uncertainties of small number statistics and without spectroscopy to confirm or refute the YSO candidates. Similarly, no clear conclusions can yet be drawn about any possible age gradients that may be present across the BRCs.Comment: 54 pages, 19 figures, accepted by A