The subthalamic nucleus : Part II: Modelling and simulation of activity

Part II starts with a systemic model of the basal ganglia to evaluate the position of the STN in the direct, indirect and hyperdirect pathways. A summary of in vitro studies is given, describing STN spontaneous activity as well as responses to depolarizing and hyperpolarizing inputs, and high frequency stimulation. STN bursting activity and the underlying ionic mechanisms are investigated. Deep brain stimulation used for symptomatic treatment of Parkinson's disease is discussed in terms of the elements that are influenced and its hypothesized mechanisms. This part of the monograph pays attention to the pedunculopontine-subthalamic connections and tries in cell cultures to mimic neurotransmitter actions of the pedunculopontine nucleus and high frequency stiulation on cultured dissociated rat subthalamic neurons. STN cell models: single and multi compartment, and system level models are discussed in relation to subthalamic function and dysfunction. Part I and II are mutually compared

The subthalamic nucleus : Part I: Development, cytology, topography and connections

This monograph on the subthalamic nucleus accentuates in Part I the gap between experimental animal and human information concerning subthalamic development, cytology, topography and connections. The light and electron microscopical cytology concerns the open nucleus concept and the neuronal types present in the STN. The cytochemistry encompasses: enzymes, NO, GRAP, calcium binding proteins, and receptors (dopamine, cannabinoid, piod, glutamate, GABA, serotonin, cholinergic, and calcium channels). The ontogeny of the subthalamic cell cord is reviewed. The topography concerns the rat, cat, baboon and human STN. The descriptions of the connections are also given from a historial point of view. Recent tracer studies on the rat nigro-subthalamic connection revealed contralateral projections

Mastication and sensibility, or the five new findings in the cat mesencephalic trigeminal nucleus

The brain even of small animals, like the rat, is complicated in its structure and its function. The hardware of the smartest personal computer is difficult to unravel. Those studying the brain know, that those brain structures that left the common evolutionary path are even harder to study. Such a structure is the mesencephalic nucleus of the trigeminal system, responsible for the sensibility of the jaw-closing muscles and the periodontium. The mesencephalic trigeminal nucleus (MTN) is a drop-like nucleus with an enormous thin tail, extending from the rostral pons along the entire caudo-rostral length of the midbrain. While all sensory ganglia of the spinal and cranial nerves are placed outside the central nervous system, the MTN, that exists of the same primary afferent neurons, is placed in the brainstem. As a consequence, this nucleus receives projections from other brain parts, projects to non-primary afferent target areas, contains a different topography and neurochemistry, in which it distinguishes itself from other primary afferent sensory ganglia of the spinal and cranial nerves. In this volume of Biomedical Reviews, the first neurochemical update on the cat MTN appears. Moreover, it stems from the Department of Anatomy, Thracian University Medical Faculty in Stara Zagora by Nikolai Lazarov and Christo Chouchkov known for their skin receptor studies and their connectivity to and in the MTN. They earned the First Dimitri Kadanoff Memorial Award truly.Biomedical Reviews 1997; 8: 21-22

Delay-induced rebounds in CO_{2} emissions and critical time-scales to meet global warming targets

While climate science debates are focused on the attainment of peak anthropogenic CO2 emissions and policy tools to reduce peak temperatures, the human‐energy‐climate system can hold “rebound” surprises beyond this peak. Following the second industrial revolution, global per capita CO_{2} emissions (c_{c}) experienced a punctuated growth of about 100% every 60 years, mainly attributable to technological development and its global spread. A model of the human‐energy‐climate system capable of reproducing past punctuated dynamics shows that rebounds in global CO_{2} emissions emerge due to delays intrinsic to the diffusion of innovations. Such intrinsic delays in the adoption and spread of low‐carbon emitting technologies, together with projected population growth, upset the warming target set by the Paris Agreement. To avoid rebounds and their negative climate effects, model calculations show that the diffusion of climate‐friendly technologies must occur with lags one‐order of magnitude shorter (i.e., ∼6 years) than the characteristic timescale of past punctuated growth in c_{c}. Radically new strategies to globally implement the technological advances at unprecedented rates are needed if the current emission goals are to be achieved

USP2a alters chemotherapeutic response by modulating redox

Cancer cells are characterized by altered ubiquitination of many proteins. The ubiquitin-specific protease 2a (USP2a) is a deubiquitinating enzyme overexpressed in prostate adenocarcinomas, where it exhibits oncogenic behavior in a variety of ways including targeting c-Myc via the miR-34b/c cluster. Here we demonstrate that USP2a induces drug resistance in both immortalized and transformed prostate cells. Specifically, it confers resistance to typically pro-oxidant agents, such as cisplatin (CDDP) and doxorubicin (Doxo), and to taxanes. USP2a overexpression protects from drug-induced oxidative stress by reducing reactive oxygen species (ROS) production and stabilizing the mitochondrial membrane potential (ΔΨ), thus impairing downstream p38 activation and triggering of apoptosis. The molecular mediator of the USP2a protective function is the glutathione (GSH). Through miR-34b/c-driven c-Myc regulation, USP2a increases intracellular GSH content, thus interfering with the oxidative cascade triggered by chemotherapeutic agents. In light of these findings, targeting Myc and/or miR-34b/c might revert chemo-resistance

Gravitational Waves from Sub-lunar Mass Primordial Black Hole Binaries - A New Probe of Extradimensions

In many braneworld models, gravity is largely modified at the electro-weak scale ~ 1TeV. In such models, primordial black holes (PBHs) with lunar mass M ~ 10^{-7}M_sun might have been produced when the temperature of the universe was at ~ 1TeV. If a significant fraction of the dark halo of our galaxy consists of these lunar mass PBHs, a huge number of BH binaries will exist in our neighborhood. Third generation detectors such as EURO can detect gravitational waves from these binaries, and can also determine their chirp mass. With a new detector designed to be sensitive at high frequency bands greater than 1 kHz, the existence of extradimensions could be confirmed.Comment: 4 pages, 1 figure, typos correcte

Detection of phosphotyrosine, insulin receptor substrate-1 and growth factor receptor-bound protein-2 in the magnocellular forebrain system and hypothalamus of cat and man

Insulin action initiated by insulin binding to its cognate receptor is performed via phosphorylation of tyrosines on substrate proteins by the receptor tyrosine kinase domain. This process involves autophosphorylation of tyrosine residues in the cytoplasmic domain of the receptor. A comparable action is mediated by nerve growth factor (NGF) and epidermal growth factor (EGF) receptors. Few articles have been directed to the morphological regional distribution in the brain of phosphotyrosine, using antibodies. The first extensive description that proved a topographical distribution for phosphotyrosine in the rat brain was conducted by Marani and Maassen. It was shown that alternating areas positive and negative for phosphotyrosine could be described. These areas showed different localizations that were in good agreement with the biochemical results obtained by others. Moreover, fetal and postnatal series confirmed the results that phosphotyrosine content is extremely high in the developing brain as compared to the mature brain. In the mature brain, the phosphotyrosine localization is also found in the neuropil, not only in neurons. High concentrations of phosphotyrosine in a regional distribution are found in the rat rhinencephalon, the cortex, the basal ganglia (mainly in neostriatum and substantia nigra), hypothalamus and the habenular nuclei. In the hippocampus, the positivity for phosphotyrosine can be detected in the pyramidal cells and the neuropil. The hippocampal subdivisions of CA1 and CA3 can be weakly discerned. Topographical studies of the distribution of insulin receptor substrate-1 (IRS-1), growth factor receptor-bound protein-2 (GRB-2) or its adaptor molecule and substrate of insulin receptor kinase (She) that complexes to GRB-2 and conducts insulin action towards the Ras complex are absent for the brain.Biomedical Reviews 1996; 5: 73-82

Gravitationally Lensed Gamma-Ray Bursts as Probes of Dark Compact Objects

If dark matter in the form of compact objects comprises a large fraction of the mass of the universe, then gravitational lensing effects on gamma-ray bursts are expected. We utilize BATSE and Ulysses data to search for lenses of different mass ranges, which cause lensing in the milli, pico, and femto regimes. Null results are used to set weak limits on the cosmological abundance of compact objects in mass ranges from 10$^{-16}$ to 10$^{-9}$ $M_{\odot}$. A stronger limit is found for a much discussed $\Omega = 0.15$ universe dominated by black holes of masses $\sim 10^{6.5} M_{\odot}$, which is ruled out at the $\sim$ 90% confidence level.Comment: 14 pages, 4 figures, fixed minor corrections. Accepted for publication in ApJ(L