SMRT-mediated co-shuttling enables export of class IIa HDACs independent of their CaM kinase phosphorylation sites

The Class IIa histone deacetylases (HDAC)4 and HDAC5 play a role in neuronal survival and behavioral adaptation in the CNS. Phosphorylation at 2/3 N-terminal sites promote their nuclear export. We investigated whether non-canonical signaling routes to Class IIa HDAC export exist because of their association with the co-repressor Silencing Mediator Of Retinoic And Thyroid Hormone Receptors (SMRT). We found that, while HDAC5 and HDAC4 mutants lacking their N-terminal phosphorylation sites (HDAC4(MUT), HDAC5(MUT)) are constitutively nuclear, co-expression with SMRT renders them exportable by signals that trigger SMRT export, such as synaptic activity, HDAC inhibition, and Brain Derived Neurotrophic Factor (BDNF) signaling. We found that SMRT's repression domain 3 (RD3) is critical for co-shuttling of HDAC5(MUT), consistent with the role for this domain in Class IIa HDAC association. In the context of BDNF signaling, we found that HDAC5(WT), which was more cytoplasmic than HDAC5(MUT), accumulated in the nucleus after BDNF treatment. However, co-expression of SMRT blocked BDNF-induced HDAC5(WT) import in a RD3-dependent manner. In effect, SMRT-mediated HDAC5(WT) export was opposing the BDNF-induced HDAC5 nuclear accumulation observed in SMRT's absence. Thus, SMRT's presence may render Class IIa HDACs exportable by a wider range of signals than those which simpl

THE LOOMING THREAT: BIOLOGICAL AND CHEMICAL WARFARE

ABSTRACT Chemical and biological weapons are capable of use across a wide spectrum of warfare, from acts of assassination and small-scale terrorism to various tactical and operational situations, both defensive and offensive, including strategic population attacks. In this era biowar is really serious concern for the mankind. This article examines the role of biotechnology in protective measures and briefly surveys the biological warfare defence capabilities of different countries

Insect pest resistance: an alternative approach for crop protection

From experience with insect resistance caused by synthetic chemical insecticides, it is clear that no single management tactic can provide lasting solutions to the insect pest problem. Biological control is a component of integrated pest management strategies that minimize insecticide spray applications and move towards ecofriendly systems of pest management. Successful utilization of host plant resistance, phytochemical products, pheromones, biological control agents such as predators, parasitoids, entomopathogenic bacteria, virus, nematodes, and fungi can help to control many destructive pests to achieve sustainable crop protection

Anesthesiologists\u27 Preferences regarding Visitor Presence during Placement of Neuraxial Labor Analgesia

Introduction: Neuraxial labor analgesia has become an integral part of modern obstetric anesthetic practice. Presence of a familiar person during its placement may be beneficial to the patient. A survey was sent to anesthesiologists practicing obstetric anesthesia in the USA to determine their views. Methods: The survey queried the following: existence of a written policy; would they allow a visitor; visitor\u27s view, sitting or standing; reasons to allow or not allow a visitor; and influence by other staff on the decision. The responses were analyzed using multiple chi-square analyses. Results: Most practitioners supported allowing a visitor during placement. Reduction of patient anxiety and fulfillment of patient request were the major reasons for allowing a visitor. Sitting position and no view of the workspace were preferred. Visitor interference and safety were cited as the major reasons for precluding a visitor. Nonanesthesia providers rarely influenced the decision. Epidural analgesia was the preferred technique. Essentially no bias was found in the responses; there was statistical uniformity regardless of procedures done per week, years in practice, professional certification, geographic region (rural, urban, or suburban), or academic, private, or government responders. Conclusion: The practice of visitor presence during the placement of neuraxial labor analgesia is gaining acceptance

Influence of root-knot nematode, Meloidogyne incognita (Kofoid & White) Chitwood infection on different plant growth parameters in Mungbean, Vigna radiata (L.) Wilczek

351-359Root-knot nematode, Meloidogyne incognita (Kofoid & White) Chitwood, is a major threat to mungbean cultivation. The pest causes a significant reduction in plant growth parameters that ultimately results in loss of grain yield. The present study was carried out under glass house condition to study the effect of different inoculum load of root-knot nematode M. incognita on plant growth, nodulation and nematode development and nutrients status of Mungbean. The results revealed a progressive decline in plant growth parameters viz., fresh and dry shoot weight and shoot length with respect to increase in inoculum level. However, fresh and dry root weight showed the opposite trend. The fresh and dry shoot weight was decreased by 44% and 66%, respectively at 4 J2s/g soil. The chlorophyll content in the leaves also decreased with the increase of inoculum level from 100-6000 J2s/pot. Nutrients contents of the plant viz. N, P, K, Ca and Mg were significantly reduced in shoots while in roots these was increased with an increase of inoculum levels. Nodulation was affected by 80% at the highest inoculum level i.e. 6000 J2s/pot. Also leghaemoglobin, bacteroid content and nitrogenase activity was reduced progressively with increased levels of nematode inoculum. Thus, the root-knot nematode, M. incognita interferes with the process of symbiotic nitrogen fixation between mungbean host and rhizobium and that can affect the quality of produce

Infrared Emission from the Nearby Cool Core Cluster Abell 2597

We observed the brightest central galaxy (BCG) in the nearby (z=0.0821) cool core galaxy cluster Abell 2597 with the IRAC and MIPS instruments on board the Spitzer Space Telescope. The BCG was clearly detected in all Spitzer bandpasses, including the 70 and 160 micron wavebands. We report aperture photometry of the BCG. The spectral energy distribution exhibits a clear excess in the FIR over a Rayleigh-Jeans stellar tail, indicating a star formation rate of ~4-5 solar masses per year, consistent with the estimates from the UV and its H-alpha luminosity. This large FIR luminosity is consistent with that of a starburst or a Luminous Infrared Galaxy (LIRG), but together with a very massive and old population of stars that dominate the energy output of the galaxy. If the dust is at one temperature, the ratio of 70 to 160 micron fluxes indicate that the dust emitting mid-IR in this source is somewhat hotter than the dust emitting mid-IR in two BCGs at higher-redshift (z~0.2-0.3) and higher FIR luminosities observed earlier by Spitzer, in clusters Abell 1835 and Zwicky 3146.Comment: Accepted at Ap

Development of stabilizing formulations of a trivalent inactivated poliovirus vaccine in a dried state for delivery in the Nanopatch™ microprojection array

The worldwide switch to inactivated polio vaccines (IPV) is a key component of the overall strategy to achieve and maintain global polio eradication. To this end, new IPV vaccine delivery systems may enhance patient convenience and compliance. In this work, we examine NanopatchTM (a solid, polymer micro-projection array) which offers potential advantages over standard needle/syringe administration including intradermal delivery and reduced antigen doses. Using trivalent IPV (tIPV) and a purpose-built evaporative dry-down system, candidate tIPV formulations were developed to stabilize tIPV during the drying process and upon storage. Identifying conditions to minimize tIPV potency losses during rehydration and potency testing was a critical first step. Various classes and types of pharmaceutical excipients (~50 total) were then evaluated to mitigate potency losses (measured through D-antigen ELISAs for IPV1, IPV2, and IPV3) during drying and storage. Various concentrations and combinations of stabilizing additives were optimized in terms of tIPV potency retention, and two candidate tIPV formulations containing a cyclodextrin and a reducing agent (e.g., glutathione), maintained ≥80% D-antigen potency during drying and subsequent storage for 4 weeks at 4˚C, and ≥60% potency for 3 weeks at room temperature with the majority of losses occurring within the first day of storage. References: * Wan, Y., et al. (in press), Development of Stabilizing Formulations of a Trivalent Inactivated Poliovirus Vaccine in a Dried State for Delivery in the Nanopatch™ Microprojection Array. Journal of Pharmaceutical Sciences. 2018. Acknowledgements: This work was funded by The World Health Organization