How tyramine β-hydroxylase controls the production of octopamine, modulating the mobility of beetles

Biogenic amines perform many kinds of important physiological functions in the central nervous system (CNS) of insects, acting as neuromodulators, neurotransmitters, and neurohormones. The five most abundant types of biogenic amines in invertebrates are dopamine, histamine, serotonin, tyramine, and octopamine (OA). However, in beetles, an important group of model and pest insects, the role of tyramine beta-hydroxylase (T beta H) in the OA biosynthesis pathway and the regulation of behavior remains unknown so far. We therefore investigated the molecular characterization and spatiotemporal expression profiles of T beta H in red flour beetles (Triboliun castaneum). Most importantly, we detected the production of OA and measured the crawling speed of beetles after dsTcT beta H injection. We concluded that TcT beta H controls the biosynthesis amount of OA in the CNS, and this in turn modulates the mobility of the beetles. Our new results provided basic information about the key genes in the OA biosynthesis pathway of the beetles, and expanded our knowledge on the physiological functions of OA in insects

Integrative concept of homeostasis: translating physiology into medicine

To truly understand living systems they must be viewed as a whole. In order to achieve this and to come to some law to which living systems obey, data obtained on cells, tissues and organs should be integrated. Because there are no such laws yet, there is usually a long path for physiological findings obtained by reductionist approaches to be translated into medical practice. The concept and accompanying equations of homeostasis presented here are aimed to develop biological laws and to bridge this gap between physiology and medicine. The concept of homeostasis takes into account energy input and output, enlisting all relevant contributors. In homeostasis, input should equal the output. What I suggest here is that if the system is out of homeostasis, the homeostasis may be regained by changing any of the input or output components in an adequate manner, not only the one that has changed first. The proposed equation should enable for new lab findings regarding any pathophysiological conditions to find a more direct use in medicine. It should also ease ‘decision making’ in medicine and make therapy development and treatment outcome more straightforward and predictable. Finally, to recognize the basic laws of living systems enables for evolutionary adaptations and processes to be understood better

Feature detection using spikes: the greedy approach

A goal of low-level neural processes is to build an efficient code extracting the relevant information from the sensory input. It is believed that this is implemented in cortical areas by elementary inferential computations dynamically extracting the most likely parameters corresponding to the sensory signal. We explore here a neuro-mimetic feed-forward model of the primary visual area (VI) solving this problem in the case where the signal may be described by a robust linear generative model. This model uses an over-complete dictionary of primitives which provides a distributed probabilistic representation of input features. Relying on an efficiency criterion, we derive an algorithm as an approximate solution which uses incremental greedy inference processes. This algorithm is similar to 'Matching Pursuit' and mimics the parallel architecture of neural computations. We propose here a simple implementation using a network of spiking integrate-and-fire neurons which communicate using lateral interactions. Numerical simulations show that this Sparse Spike Coding strategy provides an efficient model for representing visual data from a set of natural images. Even though it is simplistic, this transformation of spatial data into a spatio-temporal pattern of binary events provides an accurate description of some complex neural patterns observed in the spiking activity of biological neural networks.Comment: This work links Matching Pursuit with bayesian inference by providing the underlying hypotheses (linear model, uniform prior, gaussian noise model). A parallel with the parallel and event-based nature of neural computations is explored and we show application to modelling Primary Visual Cortex / image processsing. http://incm.cnrs-mrs.fr/perrinet/dynn/LaurentPerrinet/Publications/Perrinet04tau

Informational aspects of the haptic stimulation by the light for correction of the human functional state

Introduction. The study of the laws and principles of information processes in the biological systems of the human body in extreme forms of its activities and the development of the theory of medical information systems of such appointment, taking into account the status and trends of convergence of society, ecosystems and technology become very relevant. This state of affairs makes it possible to affirm that it is an actual scientific and applied problem of radical change of the existing paradigm of designing information systems. The purpose of the article is to specify the informational aspects of low intensity, haptic stimulation by the light, which is essential for correction of the functional state of an organism of the human being, who works in extreme conditions, to develop and study such methods and systems. Methods. Analyses of requirements, functions and systems for designing synthesis of information technologies and the control biotechnical system of correction of the functional state of an organism of the human, who works in extreme conditions. The theoretical and experimental dependences between the stimulation energy of light emission diode (LED) and the energy are transferred through the layered bio media design. Mathematical modelling and computational simulation. Comparison of these real and model data. Results. The base aspects requirements, functions and systems for designing synthesis of information technologies and the control biotechnical system of correction of the functional state of an organism of the human, who works in extreme conditions, low intensity, haptic stimulation by the light are defined. The methods for determining of intensity I0 of light emission diode, recursive expression , and formula for coefficient Cm , where M — quantity of bio media layers were developed. The bridges, which connects Maxwell’s phenomenological theory with the atomistic theory of matter and optics, were used. Computer simulation studies have confirmed the specification of requirements, functional and structural schemas of biotechnical system. Conclusions. Thanking to specification of requirements possibility-using recursive determining of the light flux intensity after every bio media layer was got. Under the effect of recurstion low computation complexity was caused. Information technology means (for automation optimal control) of the human state under external influences on the organism was developed. Further study to confirm statistical significance in representative samples of observations was opened

Cell-specific and region-specific transcriptomics in the multiple sclerosis model: Focus on astrocytes.

Changes in gene expression that occur across the central nervous system (CNS) during neurological diseases do not address the heterogeneity of cell types from one CNS region to another and are complicated by alterations in cellular composition during disease. Multiple sclerosis (MS) is multifocal by definition. Here, a cell-specific and region-specific transcriptomics approach was used to determine gene expression changes in astrocytes in the most widely used MS model, experimental autoimmune encephalomyelitis (EAE). Astrocyte-specific RNAs from various neuroanatomic regions were attained using RiboTag technology. Sequencing and bioinformatics analyses showed that EAE-induced gene expression changes differed between neuroanatomic regions when comparing astrocytes from spinal cord, cerebellum, cerebral cortex, and hippocampus. The top gene pathways that were changed in astrocytes from spinal cord during chronic EAE involved decreases in expression of cholesterol synthesis genes while immune pathway gene expression in astrocytes was increased. Optic nerve from EAE and optic chiasm from MS also showed decreased cholesterol synthesis gene expression. The potential role of cholesterol synthesized by astrocytes during EAE and MS is discussed. Together, this provides proof-of-concept that a cell-specific and region-specific gene expression approach can provide potential treatment targets in distinct neuroanatomic regions during multifocal neurological diseases

Digitization of multistep organic synthesis in reactionware for on-demand pharmaceuticals

Chemical manufacturing is often done at large facilities that require a sizable capital investment and then produce key compounds for a finite period. We present an approach to the manufacturing of fine chemicals and pharmaceuticals in a self-contained plastic reactionware device. The device was designed and constructed by using a chemical to computer-automated design (ChemCAD) approach that enables the translation of traditional bench-scale synthesis into a platform-independent digital code. This in turn guides production of a three-dimensional printed device that encloses the entire synthetic route internally via simple operations. We demonstrate the approach for the γ-aminobutyric acid receptor agonist, (±)-baclofen, establishing a concept that paves the way for the local manufacture of drugs outside of specialist facilities

Sustained delivery and molecular targeting of a therapeutic monoclonal antibody to metastases in the central nervous system of mice.

Approximately 15-40% of all cancers develop metastases in the central nervous system (CNS), yet few therapeutic options exist to treat them. Cancer therapies based on monoclonal antibodies are widely successful, yet have limited efficacy against CNS metastases, owing to the low levels of the drug reaching the tumour site. Here, we show that the encapsulation of rituximab within a crosslinked zwitterionic polymer layer leads to the sustained release of rituximab as the crosslinkers are gradually hydrolysed, enhancing the CNS levels of the antibody by approximately tenfold with respect to the administration of naked rituximab. When the nanocapsules were functionalized with CXCL13-the ligand for the chemokine receptor CXCR5, which is frequently found on B-cell lymphoma-a single dose led to improved control of CXCR5-expressing metastases in a murine xenograft model of non-Hodgkin lymphoma, and eliminated lymphoma in a xenografted humanized bone marrow-liver-thymus mouse model. Encapsulation and molecular targeting of therapeutic antibodies could become an option for the treatment of cancers with CNS metastases

Non-invasive aerosol delivery and transport of gold nanoparticles to the brain

Targeted delivery of nanoscale carriers containing packaged payloads to the central nervous system has potential use in many diagnostic and therapeutic applications. Moreover, understanding of the bio-interactions of the engineered nanoparticles used for tissue-specific delivery by non-invasive delivery approaches are also of paramount interest. Here, we have examined this issue systematically in a relatively simple invertebrate model using insects. We synthesized 5 nm, positively charged gold nanoparticles (AuNPs) and targeted their delivery using the electrospray aerosol generator. Our results revealed that after the exposure of synthesized aerosol to the insect antenna, AuNPs reached the brain within an hour. Nanoparticle accumulation in the brain increased linearly with the exposure time. Notably, electrophysiological recordings from neurons in the insect brain several hours after exposure did not show any significant alterations in their spontaneous and odor-evoked spiking properties. Taken together, our findings reveal that aerosolized delivery of nanoparticles can be an effective non-invasive approach for delivering nanoparticles to the brain, and also presents an approach to monitor the short-term nano-biointeractions

Manipulation of Mitochondria Dynamics Reveals Separate Roles for Form and Function in Mitochondria Distribution

Mitochondria shape is controlled by membrane fusion and fission mediated by mitofusins, Opa1, and Drp1, whereas mitochondrial motility relies on microtubule motors. These processes govern mitochondria subcellular distribution, whose defects are emphasized in neurons because of their polarized structure. We have studied how perturbation of the fusion/fission balance affects mitochondria distribution in Drosophila axons. Knockdown of Marf or Opa1 resulted in progressive loss of distal mitochondria and in a distinct oxidative phosphorylation and membrane potential deficit. Downregulation of Drp1 rescued the lethality and bioenergetic defect caused by neuronal Marf RNAi, but induced only a modest restoration of axonal mitochondria distribution. Surprisingly, Drp1 knockdown rescued fragmentation and fully restored aberrant distribution of axonal mitochondria produced by Opa1 RNAi; however, Drp1 knockdown did not improve viability or mitochondria function. Our data show that proper morphology is critical for proper axonal mitochondria distribution independent of bioenergetic efficiency. The health of neurons largely depends on mitochondria function, but does not depend on shape or distribution. Trevisan et al. separate the independent contribution of form and function in determining the distribution of mitochondria in axons. They show that morphology is crucial for proper axonal mitochondria distribution, independent of their bioenergetic efficiency. However, the health of neurons depends on mitochondria function, but does not depend on shape or distributio

Modulation of the host Th1 immune response in pigeon protozoal encephalitis caused by Sarcocystis calchasi

Pigeon protozoal encephalitis (PPE) is an emerging central-nervous disease of domestic pigeons (Columba livia f. domestica) reported in Germany and the United States. It is caused by the apicomplexan parasite Sarcocystis calchasi which is transmitted by Accipter hawks. In contrast to other members of the Apicomplexa such as Toxoplasma and Plasmodium, the knowledge about the pathophysiology and host manipulation of Sarcocystis is scarce and almost nothing is known about PPE. Here we show by mRNA expression profiling a significant down-modulation of the interleukin (IL)-12/IL-18/interferon (IFN)-γ axis in the brains of experimentally infected pigeons during the schizogonic phase of disease. Concomitantly, no cellular immune response was observed in histopathology while immunohistochemistry and nested PCR detected S. calchasi. In contrast, in the late central-nervous phase, IFN-γ and tumor necrosis factor (TNF) α-related cytokines were significantly up-modulated, which correlated with a prominent MHC-II protein expression in areas of mononuclear cell infiltration and necrosis. The mononuclear cell fraction was mainly composed of T-lymphocytes, fewer macrophages and B-lymphocytes. Surprisingly, the severity and composition of the immune cell response appears unrelated to the infectious dose, although the severity and onset of the central nervous signs clearly was dose-dependent. We identified no or only very few tissue cysts by immunohistochemistry in pigeons with severe encephalitis of which one pigeon repeatedly remained negative by PCR despite severe lesions. Taken together, these observations may suggest an immune evasion strategy of S. calchasi during the early phase and a delayed-type hypersensitivity reaction as cause of the extensive cerebral lesions during the late neurological phase of disease