Allatostatin-A neurons inhibit feeding behavior in adult Drosophila

How the brain translates changes in internal metabolic state or perceived food quality into alterations in feeding behavior remains poorly understood. Studies in Drosophila larvae have yielded information about neuropeptides and circuits that promote feeding, but a peptidergic neuron subset whose activation inhibits feeding in adult flies, without promoting metabolic changes that mimic the state of satiety, has not been identified. Using genetically based manipulations of neuronal activity, we show that activation of neurons (or neuroendocrine cells) expressing the neuropeptide allatostatin A (AstA) inhibits or limits several starvation-induced changes in feeding behavior in adult Drosophila, including increased food intake and enhanced behavioral responsiveness to sugar. Importantly, these effects on feeding behavior are observed in the absence of any measurable effects on metabolism or energy reserves, suggesting that AstA neuron activation is likely a consequence, not a cause, of metabolic changes that induce the state of satiety. These data suggest that activation of AstA-expressing neurons promotes food aversion and/or exerts an inhibitory influence on the motivation to feed and implicate these neurons and their associated circuitry in the mechanisms that translate the state of satiety into alterations in feeding behavior

Drawing the Blue Line: Categorizing Law Enforcement as a Protected Class Within Hate Crime Legislation

Several states have passed legislation to include law enforcement officers as a protected class within Hate Crime laws. Additionally, there is pending legislation in the United States Senate to add law enforcement officers as a protected class under the federal Hate Crimes Act. This is a step in the wrong direction for both state and federal legislatures for three main reasons. First, law enforcement officers are distinguishable from the currently protected classes. These classes have not only been marginalized in our society but have been targeted for reasons they have no control over. In contrast, including law enforcement officers as a protected class would offer protection to a group based on its choice of employment rather than an immutable characteristic. Second, many states have already implemented increased punishment for crimes committed against law enforcement. The federal government is no exception, as it has also already provided for law enforcement safety within its code. Finally, this trend could potentially have serious consequences across the board

Outcomes and safety of concomitant nevirapine and rifampicin treatment under programme conditions in Malawi.

SETTING: Thyolo District Hospital, rural Malawi. OBJECTIVES: To report on 1) clinical, immunological and virological outcomes and 2) safety among human immunodeficiency virus (HIV) infected patients with tuberculosis (TB) who received concurrent nevirapine (NVP) and rifampicin (RMP) based treatment. DESIGN: Retrospective cohort study. METHODS: Analysis of programme data, June-December 2007. RESULTS: Of a total of 156 HIV-infected TB patients who started NVP-based antiretroviral treatment, 136 (87%) completed TB treatment successfully, 16 (10%) died and 5 (4%) were transferred out. Mean body weight and CD4 gain (adults) were respectively 4.4 kg (95%CI 3.3-5.4) and 140 cells/mm(3) (95%CI 117-162). Seventy-four per cent of patients who completed TB treatment and had a viral load performed (n = 74) had undetectable levels (<50 copies/ml), while 17 (22%) had a viral load of 50-1000 copies/ml. Hepatotoxicity was present in 2 (1.3%) patients at baseline. Two patients developed Grade 2 and one developed Grade 3 alanine transaminase enzyme elevations during TB treatment (incidence rate per 10 years of follow-up 4.2, 95%CI 1.4-13.1). There were no reported deaths linked to hepatotoxicity. CONCLUSIONS: In a rural district in Malawi, concomitant NVP and RMP treatment is associated with good TB treatment outcomes and appears safe. Further follow-up of patients would be useful to ascertain the longer-term effects of this concurrent treatment

Dissipative Taylor-Couette flows under the influence of helical magnetic fields

The linear stability of MHD Taylor-Couette flows in axially unbounded cylinders is considered, for magnetic Prandtl number unity. Magnetic fields varying from purely axial to purely azimuthal are imposed, with a general helical field parameterized by \beta=B_\phi/B_z. We map out the transition from the standard MRI for \beta=0 to the nonaxisymmetric Azimuthal MagnetoRotational Instability (AMRI) for \beta\to \infty. For finite \beta, positive and negative wave numbers m, corresponding to right and left spirals, are no longer identical. The transition from \beta=0 to \beta\to\infty includes all the possible forms of MRI with axisymmetric and nonaxisymmetric modes. For the nonaxisymmetric modes, the most unstable mode spirals in the opposite direction to the background field. The standard (\beta=0) MRI is axisymmetric for weak fields (including the instability with the lowest Reynolds number) but is nonaxisymmetric for stronger fields. If the azimuthal field is due in part to an axial current flowing through the fluid itself (and not just along the central axis), then it is also unstable to the nonaxisymmetric Tayler instability, which is most effective without rotation. For large \beta this instability has wavenumber m=1, whereas for \beta\simeq 1 m=2 is most unstable. The most unstable mode spirals in the same direction as the background field.Comment: 9 pages, 11 figure

Metabotropic glutamate receptor 2/3 (mGluR2/3) activation suppresses TRPV1 sensitization in mouse, but not human sensory neurons

AbstractThe use of human tissue to validate putative analgesic targets identified in rodents is a promising strategy for improving the historically poor translational record of preclinical pain research. We recently demonstrated that in mouse and human sensory neurons, agonists for metabotropic glutamate receptors 2 and 3 (mGluR2/3) reduce membrane hyperexcitability produced by the inflammatory mediator prostaglandin E2(PGE2). Previous rodent studies indicate that mGluR2/3 can also reduce peripheral sensitization by suppressing inflammation-induced sensitization of TRPV1. Whether this observation similarly translates to human sensory neurons has not yet been tested. We found that activation of mGluR2/3 with the agonist APDC suppressed PGE2-induced sensitization of TRPV1 in mouse, but not human, sensory neurons. We also evaluated sensory neuron expression of the gene transcripts for mGluR2 (Grm2), mGluR3 (Grm3), and TRPV1 (Trpv1). The majority ofTrpv1+mouse and human sensory neurons expressedGrm2and/orGrm3, and in both mice and humans,Grm2was expressed in a greater percentage of sensory neurons thanGrm3. Although we demonstrated a functional difference in the modulation of TRPV1 sensitization by mGluR2/3 activation between mouse and human, there were no species differences in the gene transcript colocalization of mGluR2 or mGluR3 with TRPV1 that might explain this functional difference. Taken together with our previous work, these results suggest that mGluR2/3 activation suppresses only some aspects of human sensory neuron sensitization caused by PGE2. These differences have implications for potential healthy human voluntary studies or clinical trials evaluating the analgesic efficacy of mGluR2/3 agonists or positive allosteric modulators.</jats:p

Low-cost, pseudo-Halbach dipole magnets for NMR

We present designs for compact, inexpensive and strong dipole permanent magnets aimed primarily at magnetic resonance applications where prepolarization and detection occur at different locations. Low-homogeneity magnets with a 7.5 mm bore size and field up to nearly 2 T are constructed using low-cost starting materials, standard workshop tools and only few hours of labor – an achievable project for a student or postdoc with spare time. As an application example we show how our magnet was used to polarize the nuclear spins in approximately 1 mL of pure [$^{13}$C]-methanol prior to detection of its high-resolution NMR spectrum at zero field (measurement field below 10$^{-10}$ T), where signals appear at multiples of the carbon-hydrogen spin-spin coupling frequency $^{1}$J$_{CH}$=140.7(1) Hz.This work has received support from the European Research Council (author DS, grant agreement FP7-205119 R-EvolutioN-MR) and from the European Commission’s Seventh Framework Program (author MCDT under the Marie Curie International Outgoing Fellowship Programme, grant agreement FP7-625054 ODMR-CHEM; author DS, 2007–2013)

Compartmentalization and axon guidance in the Drosophila brain

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2005.Includes bibliographical references.The Drosophila brain is composed of many morphologically and functionally distinct processing centers and brain morphogenesis depends on the creation and maintenance of distinct boundaries between adjacent regions to prevent cells from mixing. In the Drosophila visual system, I have found that Slit and Roundabout (Robo) proteins function to prevent cells from adjacent compartments from mixing. I have defined a boundary between two distinct compartments, the lamina and lobula, and find that the secreted ligand Slit is present in the lamina, while the Robo receptors (Robo, Robo2 and Robo3) are expressed on lobula neurons. I examined the function of theses proteins by identifying a tissue-specific allele of slit and creating transgenic RNAi flies that inhibit the expression of the Robo proteins. Loss of Slit or all three Robo proteins in the visual system results in the invasion of lobula neurons into the lamina. Mixing of cells at the lamina/lobula boundary results in glial cell mispositioning and aberrant photoreceptor axon targeting. Thus, Slit and Robo proteins are required to restrict movement of cells across the lamina/lobula boundary. Additionally, I have characterized Ptpmeg, a highly conserved protein tyrosine phosphatase (PTP). In addition to the C-terminus PTP domain, Ptpmeg contains a central PDZ domain and an N-terminus FERM domain. The in vivo role of this family of proteins is unknown. To explore the function of Ptpmeg in flies, mutants were generated by targeted gene disruption. Examination of the adult nervous system of Ptpmeg mutants reveals a defect in the mushroom bodies (MB), brain structures required for olfactory learning and memory. In mutant animals, the MB lobes are disorganized and fail to elaborate their characteristic structure. I find(cont.) that Ptpmeg is expressed on MB axons and targeted knockdown of Ptpmeg in the MB results in similar defects as seen in homozygous mutants. Thus, the MB neurons appear to require Ptpmeg for proper formation.by Timothy D. Tayler.Ph.D

Low-cost, pseudo-Halbach dipole magnets for NMR

We present designs for compact, inexpensive and strong dipole permanent magnets aimed primarily at magnetic resonance applications where prepolarization and detection occur at different locations. Low-homogeneity magnets with a 7.5 mm bore size and field up to nearly 2 T are constructed using low-cost starting materials, standard workshop tools and only few hours of labor – an achievable project for a student or postdoc with spare time. As an application example we show how our magnet was used to polarize the nuclear spins in approximately 1 mL of pure [$^{13}$C]-methanol prior to detection of its high-resolution NMR spectrum at zero field (measurement field below 10$^{-10}$ T), where signals appear at multiples of the carbon-hydrogen spin-spin coupling frequency $^{1}$J$_{CH}$=140.7(1) Hz.This work has received support from the European Research Council (author DS, grant agreement FP7-205119 R-EvolutioN-MR) and from the European Commission’s Seventh Framework Program (author MCDT under the Marie Curie International Outgoing Fellowship Programme, grant agreement FP7-625054 ODMR-CHEM; author DS, 2007–2013)

The published research paper: is it an important indicator of successful operational research at programme level?

Is a published research paper an important indicator of successful operational research at programme level in low-income countries? In academia, publishing in peer-reviewed scientific journals is highly encouraged and strongly pursued for academic recognition and career progression. In contrast, for those who engage in operational research at programme level, there is often no necessity or reward for publishing the results of research studies; it may even be criticized as being an unnecessary detraction from programme-related work. We present arguments to support publishing operational research from low-income countries; we highlight some of the main reasons for failure of publication at programme level and suggest ways forward