Binge Alcohol Drinking Alters Synaptic Processing of Executive and Emotional Information in Core Nucleus Accumbens Medium Spiny Neurons

The nucleus accumbens (NAc) is a forebrain region mediating the positive-reinforcing properties of drugs of abuse, including alcohol. It receives glutamatergic projections from multiple forebrain and limbic regions such as the prefrontal cortex (PFCx) and basolateral amygdala (BLA), respectively. However, it is unknown how NAc medium spiny neurons (MSNs) integrate PFCx and BLA inputs, and how this integration is affected by alcohol exposure. Because progress has been hampered by the inability to independently stimulate different pathways, we implemented a dual wavelength optogenetic approach to selectively and independently stimulate PFCx and BLA NAc inputs within the same brain slice. This approach functionally demonstrates that PFCx and BLA inputs synapse onto the same MSNs where they reciprocally inhibit each other pre-synaptically in a strict time-dependent manner. In alcohol-naïve mice, this temporal gating of BLA-inputs by PFCx afferents is stronger than the reverse, revealing that MSNs prioritize high-order executive processes information from the PFCx. Importantly, binge alcohol drinking alters this reciprocal inhibition by unilaterally strengthening BLA inhibition of PFCx inputs. In line with this observation, we demonstrate that in vivo optogenetic stimulation of the BLA, but not PFCx, blocks binge alcohol drinking escalation in mice. Overall, our results identify NAc MSNs as a key integrator of executive and emotional information and show that this integration is dysregulated during binge alcohol drinking.

A Meticulous Review on Coumarin Derivatives as a Marvel Medication for Thousands of Ailments

Coumarin derivatives have progressively enticed medicinal chemists because of their potential role in preventing and treating ailments. They epitomize a key motif nucleus in heterocyclic chemistry and a privileged structure in medicinal chemistry because of its extensive-range pharmacological activity. Regardless of the advancement in medicine over the past century, cancer is still remain the prominent source of death in the world and it makes indispensible needs to synthesize the compounds with coumarin as the core nucleus. Synthesis of various coumarin derivatives and evaluation of their pharmacological effects can perceive a solution to certain enigmatic demands in health sector. This review article is fixated on different synthetic routes of coumarin nucleus containing compounds. The review article also highlights different biological activities such as anticancer, antibacterial, anti- inflammatory, antihyperlipidemic and enzyme inhibition activities.

Calculation of quadrupole deformation parameter β2 from reduced transition probability B(E2) for 0+1 → 2+1 transitions at even-even 62-68Zn isotopes

In this work the excited energy levels, reduced transition probabilities B(E2)↑, intrinsic quadrupole moments, and deformation parameters have been calculated for 62-68Zn isotopes with neutrons number N = 32, 34, 36 and 38. NuSheIIX code has been applied for all energy states of fp-shell nuclei. Shell-model calculations for the zinc isotopes have been carried out with active particles distributed in the lp3/2, 0f5/2, and lp1/2 orbits outside doubly magic closed 56Ni core nucleus. By using f5p model space and f5pvh interaction, the theoretical results have been obtained and compared with the available experimental results. The excited energies values, electric transition probability B(E2), intrinsic quadrupole moment Q0, and deformation parameters β2 have appeared in complete agreement with the experimental values. As well as, the energy levels have been confirmed and determined for the angular momentum and parity of experimental values that have not been well established and determined experimentally. On the other hand, it has been predicted some of the new energy levels and electric transition probabilities for the 62-68Zn isotopes under this study which were previously unknown in experimental information.

Investigating Structural Requirements of Some Pyrimidine-linked Benzimidazole Derivatives as Anticancer Agents Against MCF-7 Cancerous Cell Line Through the use of 2D and 3D QSARs

Background: Cancer is an extremely fast, unrestrained and pathological propagation of cells. Yet there is no cancer treatment that is 100% efficient against scattered cancer. Heterocycles have been considered as a boon to treat several cancers of which pyrimidine is a core nucleus and holds an important place in cancer chemotherapy which is reflected in the use of drugs such as 5-fluorouracil, erlotinib, gefitinib and caneratinib. Also, many good antitumor active agents possess benzimidazoleas its core nucleus. Objective: To design novel pyrimidine-linked benzimidazoles and to explore their structural requirements related to anticancer potential. Methods: 2D and 3D Quantitative structure–activity relationship (QSAR) studies were carried out on a series of already synthesized 27 pyrimidine-benzimidazole derivatives. Results: Statistically significant and optimum 2D-QSAR model was developed by using step-wise variable multiple linear regression method, yielding correlation coefficient r2 = 0.89, cross-validated squared correlation coefficient q2 = 0.79 and external predictive ability of pred_r2 = 0.73 Best 3D-QSAR model was developed by employing molecular field analysis using step-wise variable k-nearest neighbor method which showed good correlative and predictive abilities in terms of q2 =0.77 and pred_r2= 0.93. Conclusion: These 2D and 3D models were found to give dependable indications which helped to optimize the pyrimidine-benzimidazole derivatives of the data set. The data yielded by 2D- QSAR and 3D-QSAR models will aid in giving better perceptions about structural requirements for developing newer anticancer agents.

TEACHER’S APPRECIATION: POLITICAL PRIORITY, TENSION OR UNCERTAINTY?

The article aims to analyze the representations of teacher appreciation by senior Pedagogy students. In the first part, we reflect on teacher appreciation in educational policies, based on the description of the teaching profession in Brazil and its “instability”, taking the political ideology as a “social constant”. In the second part, we use the Theory of Social Representations and the understanding of educational policies, from the Core Nucleus Theory, in order to understand how the social representations of senior Pedagogy students on teacher appreciation are structured. Finally, we traced the research paths and, through prototypical analyzes, we studied the social representations of these students.

Matter density distribution and longitudinal form factors for the ground and excited states of 17Ne exotic nucleus

The two-frequency shell model approach is used to calculate theground state matter density distribution and the corresponding rootmean square radii of the two-proton17Ne halo nucleus with theassumption that the model space of 15O core nucleus differ from themodel space of extra two loosely bound valence protons. Twodifferent size parameters bcore and bhalo of the single particle wavefunctions of the harmonic oscillator potential are used. Thecalculations are carried out for different configurations of the outerhalo protons in 17Ne nucleus and the structure of this halo nucleusshows that the dominant configuration when the two halo protons inthe 1d5/2 orbit (15O core plus two protons halo in pure 1d5/2 orbit). Thecalculated matter density distribution in terms of the two-frequencyshell model is compared with the calculated one in terms one sizeparameter for all orbits to illustrate the effect of introducing one ortwo size parameters in calculations. The longitudinal form factors forelastic C0 and inelastic C2 electron scattering from 17Ne nucleus arecalculated for the considered configurations and for three states ofeach configuration which are the ground state ( JT  1 2 3 2 ) andthe first two excited states ( JT  3 2 3 2 ) and ( JT  5 2 3 2 ).The electric transition strengths B(C2) are calculated for the excitedstates and for the effective nucleon charges which are used in thiswork and compared with the experimental values.

Anticancer Activity of Aminoacid Linked Novel 4-Methylumbelliferone Derivatives

Background: Cancer is a disease of high mortality. The therapeutic agents currently available are insufficient to cure it and are associated with serious side effects. 4-methylumbelliferone is a natural product containing benzo-α-pyrones as a central nucleus. Benzo-α-pyrone is a privileged moiety having multifarious biological activities including anticancer activity. A series of compounds were synthesized taking 4-methylumbelliferone as a core nucleus and screened for their anticancer activity against HeLa cancer cell line. Methods: The 4-methylumbelliferone was linked with aminoacids using chloroacetyl chloride or ethyl chloroacetate as linker. The N-methylmorpholine and isobutylchloroformate protocol was used for amidic coupling. The final compounds were tested against the HeLa cancer cell lines using SRB assay protocol. Results: Three compounds have shown significant anticancer activity viz 9a, 12f and 15l having GI50 (µg/ml) value of, 56.1, 30.9 and 50.9, respectively. Other compound 9f and 13 showed weak anticancer activity having GI50 (µg/ml) value of 97.2 and 71.1, respectively. Conclusion: It has been found that the synthesized derivatives have inhibitory effect on the growth of cancer cell line. Compound 12f has been found as the most active compound of the synthesized series.

“Crack, Reduce, and Implant”: A Safe Phaco Technique in a Case with Hard Brown Cataract

This report describes two maneuvers in different steps of phaco surgery in a case with hard cataract, which provide debulking of the central dense nucleus and prevents posterior capsule rupture (PCR). In the current case, clear corneal incisions were created, and anterior chamber was filled with ophthalmic viscosurgical device (OVD). Anterior capsule was punctured, and capsulorhexis was completed. Nucleus was cracked into two halves following vertical groove formation. Core nucleus was hollowed sideward bilaterally in the capsular bag. Nuclear halves were removed from capsular bag, and each one was pushed to one side on the iris plane. Capsular bag was inflated with OVD, and intraocular lens (IOL) was implanted. Nuclear halves were removed in confidence. The presented maneuvers initially reduce dense nucleus load in the safe zone and allow surgeon to use IOL as a barrier to protect floppy posterior capsule from early steps of the surgery.

Synthesis of cis-hydrindan-2,4-diones bearing an all-carbon quaternary center by a Danheiser annulation

A straightforward synthetic entry to functionalized hydrindane compounds based on a rapid assembly of the core nucleus by a Danheiser cycloaddition is reported. Valuable bicyclic building blocks containing the fused five and six-membered carbocyclic ring system can be achieved in only four steps from a simple acyclic β-keto ester.