A revised structure of fluorescein mercuric acetate

With the help of NMR spectroscopy the structure assignment of fluorescein mercuric acetate is corrected to 4',5'-bis(acetoxymercury)fluorescein.     

Base composition analysis of oligonucleotides containing apurinic sites.

Upon base composition analysis, oligonucleotides which are labeled at the 3'-terminus with fluorescein or biotin generate an additional, late eluting peak in the HPLC chromatogram. Investigation of this effect revealed the haptens acted as apurinic sites, and phosphodiesterase cleavage of the phosphate bond between the upstream nucleotide and apurinic site is inhibited. Extension of this work with a base-stable apurinic site inserted into all possible junctures of 5'-TGAC-3' tetramers showed this to be a general effect. As a consequence of this work, acid-catalyzed depurination resulting in apurinic sites can be monitored in oligonucleotide synthesis.     

Structural prediction and comparative docking studies of psychrophilic ��- Galactosidase with lactose, ONPG and PNPG against its counter parts of mesophilic and thermophilic enzymes

Enzymes from psychrophiles catalyze the reactions at low temperatures with higher specific activity. Among all the psychrophilic enzymes produced, cold active β-galactosidase from marine psychrophiles revalorizes a new arena in numerous areas at industrial level. The hydrolysis of lactose in to glucose and galactose by cold active β-galactosidase offers a new promising approach in removal of lactose from milk to overcome the problem of lactose intolerance. Herein we propose, a 3D structure of cold active β-galactosidase enzyme sourced from Pseudoalteromonas haloplanktis by using Modeler 9v8 and best model was developed having 88% of favourable region in ramachandran plot. Modelling was followed by docking studies with the help of Auto dock 4.0 against the three substrates lactose, ONPG and PNPG. In addition, comparative docking studies were also performed for the 3D model of psychrophilic β-galactosidase with mesophilic and thermophilic enzymes. Docking studies revealed that binding affinity of enzyme towards the three different substrates is more for psychrophilic enzyme when compared with mesophilic and thermophilic enzymes. It indicates that the enzyme has high specific activity at low temperature when compared with mesophilic and thermophilic enzymes.     

Long non‐coding RNAs in melanoma

Melanoma is the most lethal cutaneous cancer with a highly aggressive and metastatic phenotype. While recent genetic and epigenetic studies have shed new insights into the mechanism of melanoma development, the involvement of regulatory non‐coding RNAs remain unclear. Long non‐coding RNAs (lncRNAs) are a group of endogenous non‐protein‐coding RNAs with the capacity to regulate gene expression at multiple levels. Recent evidences have shown that lncRNAs can regulate many cellular processes, such as cell proliferation, differentiation, migration and invasion. In the melanoma, deregulation of a number of lncRNAs, such as HOTAIR, MALAT1, BANCR, ANRIL, SPRY‐IT1 and SAMMSON, have been reported. Our review summarizes the functional role of lncRNAs in melanoma and their potential clinical application for diagnosis, prognostication and treatment.     

Reconstituting Corticostriatal Network on-a-Chip Reveals the Contribution of the Presynaptic Compartment to Huntington’s Disease

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Changes in odor quality discrimination following recovery from olfactory nerve transection

Following recovery from olfactory nerve transection, animals regain their ability to discriminate between odors. Odor discrimination is restored after new neurons establish connections with the olfactory bulb. However, it is not known if the new connections alter odor quality perception. To address this question, 20 adult hamsters were first trained to discriminate between cinnamon and strawberry odors. After reaching criterion (> or = 90% correct response), half of the animals received a bilateral nerve transection (BTX) and half a surgical sham procedure. Animals were not tested again until day 40, a point in recovery when connections are re-established with the bulb. When BTX animals were tested without food reinforcement, they could not perform the odor discrimination task. Sham animals, however, could discriminate, demonstrating that the behavioral response had not been extinguished during the 40 day period. When reinforcement was resumed, BTX animals were able to discriminate between cinnamon and strawberry after four test sessions. In addition, their ability to discriminate between these two familiar odors was no different than that of BTX and sham animals tested with two novel odors, baby powder and coffee. These findings suggest that, after recovery from nerve transection, there are alterations in sensory perception and that restoration of odor quality discrimination requires that the animal must again learn to associate individual odor sensations with a behavioral response.      

Structure_threader: An improved method for automation and parallelization of programs structure,fastStructure and MavericK on multicore CPU systems

Structure_threader is a program to parallelize multiple runs of genetic clustering software that does not make use of multithreading technology (structure , fastStructure and MavericK) on multicore computers. Our approach was benchmarked across multiple systems and displayed great speed improvements relative to the single‐threaded implementation, scaling very close to linearly with the number of physical cores used. Structure_threader was compared to previous software written for the same task—ParallelStructure and StrAuto and was proven to be the faster (up to 25% faster) wrapper under all tested scenarios. Furthermore, Structure_threader can perform several automatic and convenient operations, assisting the user in assessing the most biologically likely value of ‘K’ via implementations such as the “Evanno,” or “Thermodynamic Integration” tests and automatically draw the “meanQ” plots (static or interactive) for each value of K (or even combined plots). Structure_threader is written in python 3 and licensed under the GPLv3. It can be downloaded free of charge at https://github.com/StuntsPT/Structure_threader .     

Brief Subthreshold Events Can Act as Hebbian Signals for Long-Term Plasticity

Background

Action potentials are thought to be determinant for the induction of long-term synaptic plasticity, the cellular basis of learning and memory. However, neuronal activity does not lead systematically to an action potential but also, in many cases, to synaptic depolarizing subthreshold events. This is particularly exemplified in corticostriatal information processing. Indeed, the striatum integrates information from the whole cerebral cortex and, due to the membrane properties of striatal medium spiny neurons, cortical inputs do not systematically trigger an action potential but a wide range of subthreshold postsynaptic depolarizations. Accordingly, we have addressed the following question: does a brief subthreshold event act as a Hebbian signal and induce long-term synaptic efficacy changes?

Methodology/Principal Findings

Here, using perforated patch-clamp recordings on rat brain corticostriatal slices, we demonstrate, that brief (30 ms) subthreshold depolarizing events in quasi-coincidence with presynaptic activity can act as Hebbian signals and are sufficient to induce long-term synaptic plasticity at corticostriatal synapses. This “subthreshold-depolarization dependent plasticity” (SDDP) induces strong, significant and bidirectional long-term synaptic efficacy changes at a very high occurrence (81%) for time intervals between pre- and postsynaptic stimulations (Δt) of −110<Δt<+110 ms. Such subthreshold depolarizations are able to induce robust long-term depression (cannabinoid type-1 receptor-activation dependent) as well as long-term potentiation (NMDA receptor-activation dependent).

Conclusion/Significance

Our data show the existence of a robust, reliable and timing-dependent bidirectional long-term plasticity induced by brief subthreshold events paired with presynaptic activity. The existence of a subthreshold-depolarization dependent plasticity extends considerably, beyond the action potential, the neuron''s capabilities to express long-term synaptic efficacy changes.     

Heavy-ion anisotropy measured by ALTEA in the International Space Station

The uneven shielding of the International Space Station from the vessel hull, racks and experiments produces a modulation of the internal radiation environment. A detailed knowledge of this environment, and therefore of the Station's shielding effectiveness, is mandatory for an accurate assessment of radiation risk. We present here the first 3D measurements of the Station's radiation environment, discriminating particle trajectories and LET, made possible using the detection capability of the ALTEA-space detector. We provide evidence for a strong (factor ≈ 3) anisotropy in the inner integral LET for high-LET particles (LET > 50?keV/μm) showing a minimum along the longitudinal station axis (most shielded) and a maximum normal to it. Integrating over all measured LETs, the anisotropy is strongly reduced, showing that unstopped light ions plus the fragments produced by heavier ions approximately maintain flux/LET isotropy. This suggests that, while changing the quality of radiation, the extra shielding along the station main axis is not producing a benefit in terms of total LET. These features should be taken into account (1) when measuring radiation with detectors that cannot distinguish the direction of the impinging radiation or that are unidirectional, (2) when planning radiation biology experiments on the ISS, and (3) when simulating the space radiation environment for experiments on the ground. A novel analysis technique that fully exploits the ability to retrieve the angular distribution of the radiation is also presented as well as the angular particle flux and LET characteristic of three geomagnetic zones measured during 2009 by the ALTEA-space detector. This technique is applied to the ALTEA-space detector, but a wider applicability to other detectors is suggested.     

Affecting Pseudomonas aeruginosa Phenotypic Plasticity by Quorum Sensing Dysregulation Hampers Pathogenicity in Murine Chronic Lung Infection

In Pseudomonas aeruginosa quorum sensing (QS) activates the production of virulence factors, playing a critical role in pathogenesis. Multiple negative regulators modulate the timing and the extent of the QS response either in the pre-quorum or post-quorum phases of growth. This regulation likely increases P. aeruginosa phenotypic plasticity and population fitness, facilitating colonization of challenging environments such as higher organisms. Accordingly, in addition to the factors required for QS signals synthesis and response, also QS regulators have been proposed as targets for anti-virulence therapies. However, while it is known that P. aeruginosa mutants impaired in QS are attenuated in their pathogenic potential, the effect of mutations causing a dysregulated timing and/or magnitude of the QS response has been poorly investigated so far in animal models of infection. In order to investigate the impact of QS dysregulation on P. aeruginosa pathogenesis in a murine model of lung infection, the QteE and RsaL proteins have been selected as representatives of negative regulators controlling P. aeruginosa QS in the pre- and post-quorum periods, respectively. Results showed that the qteE mutation does not affect P. aeruginosa lethality and ability to establish chronic infection in mice, despite causing a premature QS response and enhanced virulence factors production in test tube cultures compared to the wild type. Conversely, the post-quorum dysregulation caused by the rsaL mutation hampers the establishment of P. aeruginosa chronic lung infection in mice without affecting the mortality rate. On the whole, this study contributes to a better understanding of the impact of QS regulation on P. aeruginosa phenotypic plasticity during the infection process. Possible fallouts of these findings in the anti-virulence therapy field are also discussed.