Intra-BLA alteration of interneurons' modulation of activity in rats, reveals a dissociation between effects on anxiety symptoms and extinction learning.

The basolateral amygdala (BLA) is a dynamic brain region involved in emotional experiences and subject to long-term plasticity. The BLA also modulates activity, plasticity, and related behaviors associated with other brain regions, including the mPFC and hippocampus. Accordingly, intra-BLA plasticity can be expected to alter both BLA-dependent behaviors and behaviors mediated by other brain regions.

Selective knockdown of GABAA-α2 subunit in the dorsal dentate gyrus in adulthood induces anxiety, learning and memory deficits and impairs synaptic plasticity.

Animal studies and clinical trials suggest that maintenance of gamma-aminobutyric acid (GABA)-ergic activity may be crucial in coping with stressful conditions, anxiety and mood disorders. Drugs highly efficient in promoting anxiolysis were shown to activate this system, particularly via the α2-subunit of type A receptors (GABAA α2). Given the high expression of GABAA α2 in the dentate gyrus (DG) sub-field of the hippocampus, we sought to examine whether manipulation of the α2 subunit in this area will evoke changes in emotional behaviour, memory and learning as well as in synaptic plasticity.

Emergence of slip-ideal-slip behavior in tip-links serve as force filters of sound in hearing.

Tip-links in the inner ear convey force from sound and trigger mechanotransduction. Here, we present evidence that tip-links (collectively as heterotetrameric complexes of cadherins) function as force filters during mechanotransduction. Our force-clamp experiments reveal that the tip-link complexes show slip-ideal-slip bond dynamics.

Emerging role of heat shock proteins in cardiovascular diseases.

Heat Shock Proteins (HSPs) are evolutionarily conserved proteins from prokaryotes to eukaryotes. They are ubiquitous proteins involved in key physiological and cellular pathways (viz. inflammation, immunity and apoptosis).

Phenolic Phytochemicals for Prevention and Treatment of Colorectal Cancer: A Critical Evaluation of In Vivo Studies.

Colorectal cancer (CRC) is the third most diagnosed and second leading cause of cancer-related death worldwide. Limitations with existing treatment regimens have demanded the search for better treatment options. Different phytochemicals with promising anti-CRC activities have been reported, with the molecular mechanism of actions still emerging.

The role of hippocampal CaMKII in resilience to trauma-related psychopathology.

Traumatic stress exposure can form persistent trauma-related memories. However, only a minority of individuals develop post-traumatic stress disorder (PTSD) symptoms upon exposure. We employed a rat model of PTSD, which enables differentiating between exposed-affected and exposed-unaffected individuals.

Engineering the Nonmorphing Point of Actuation for Controlled Drug Release by Hydrogel Bilayer across the pH Spectrum.

Hydrogel-based pH-responsive bilayer actuators exhibit bidirectional actuation due to the differences in the concentration gradient developed across the thickness, the volume expansion due to swelling, and the mechanical stiffness of the layers involved. At a pH value (point), where the sum of these factors generates moments of equal magnitudes, the moments cancel each other and result in no net actuation. This pH point is termed here as a "nonmorphing point".

Disordered regions endow structural flexibility to shell proteins and function towards shell-enzyme interactions in 1,2-propanediol utilization microcompartment.

Intrinsically disordered regions in proteins have been functionally linked to the protein-protein interactions and genesis of several membraneless organelles. Depending on their residual makeup, hydrophobicity or charge distribution they may remain in extended form or may assume certain conformations upon biding to a partner protein or peptide. The present work investigates the distribution and potential roles of disordered regions in the integral proteins of 1,2-propanediol utilization microcompartments.

A Major Shell Protein of 1,2-Propanediol Utilization Microcompartment Conserves the Activity of Its Signature Enzyme at Higher Temperatures.

A classic example of an all-protein natural nano-bioreactor, the bacterial microcompartment is a prokaryotic organelle that confines enzymes in a small volume enveloped by an outer protein shell. These protein compartments metabolize specific organic molecules, allowing bacteria to survive in restricted nutrient environments. In this work, 1,2-propanediol utilization microcompartment (PduMCP) was used as a model to study the effect of molecular confinement on the stability and catalytic activity of native enzymes in the microcompartment.

Prostate cancer: Therapeutic prospect with herbal medicine.

Prostate cancer (PCa) is a major cause of morbidity and mortality in men worldwide. A geographic variation on the burden of the disease suggested that the environment, genetic makeup, lifestyle, and food habits modulate one's susceptibility to the disease. Although it has been generally thought to be an older age disease, and awareness and timely execution of screening programs have managed to contain the disease in the older population over the last decades, the incidence is still increasing in the population younger than 50.

Anisotropy in mechanical unfolding of protein upon partner-assisted pulling and handle-assisted pulling.

Proteins as force-sensors respond to mechanical cues and regulate signaling in physiology. Proteins commonly connect the source and response points of mechanical cues in two conformations, independent proteins in end-to-end geometry and protein complexes in handshake geometry. The force-responsive property of independent proteins in end-to-end geometry is studied extensively using single-molecule force spectroscopy (SMFS).

Pharmacognostical and phytochemical studies of ( [Linn.] sweet) fruit.

Background: (Linn.) Sweet (), generally called as "" is a plant of high medicinal importance. The plant possesses several beneficial effects such as cooling, laxative, digestive, analgesic, anti-inflammatory, astringent, diuretic, expectorant, antihelmintic, aphrodisiac, and demulcent which is widely used in the Ayurveda system of medicine.

Reducing glutamic acid decarboxylase in the dorsal dentate gyrus attenuates juvenile stress induced emotional and cognitive deficits.

A high degree of regional, temporal and molecular specificity is evident in the regulation of GABAergic signaling in stress-responsive circuitry, hampering the use of systemic GABAergic modulators for the treatment of stress-related psychopathology. Here we investigated the effectiveness of local intervention with the GABA synthetic enzymes GAD65 and GAD67 in the dorsal dentate gyrus (dDG) ventral DG (vDG) to alleviate anxiety-like behavior and stress-induced symptoms in the rat. We induced shRNA-mediated knock down of either GAD65 or GAD67 with lentiviral vectors microinjected into the dDG or vDG of young adult male rats and examined anxiety behavior, learning and memory performance.

Structurally distinct unfolding intermediates formed from a staphylococcal capsule-producing enzyme retained NADPH binding activity.

CapF, a capsule-producing enzyme expressed by , binds NADPH and exists as a dimer in the aqueous solution. Many other capsule-producing virulent bacteria also express CapF orthologs. To understand the folding-unfolding mechanism of CapF, herein a recombinant CapF (rCapF) was individually investigated using urea and guanidine hydrochloride (GdnCl).

Probe into a multi-protein prokaryotic organelle using thermal scanning assay reveals distinct properties of the core and the shell.

Background: Bacterial microcompartments represent the only reported category of prokaryotic organelles that are capable of functioning as independent bioreactors. In this organelle, a biochemical pathway with all the enzyme machinery is encapsulated within an all protein shell. The shell proteins and the enzymes have distinct structural features.

Tissue distribution of mercury and copper after Aarogyavardhini Vati treatment in rat model of CCl induced chronic hepatotoxicity.

Background: Aarogyavardhini Vati is a classical Ayurvedic herbomineral formulation. It contains mercury and copper compounds as principal minerals along with other minerals and herbal ingredients. Aarogyavardhini Vati is indicated in chronic liver ailments.

Variable Mutations at the p53-R273 Oncogenic Hotspot Position Leads to Altered Properties.

Mutations in p53 protein, especially in the DNA-binding domain, is one of the major hallmarks of cancer. The R273 position is a DNA-contact position and has several oncogenic variants. Surprisingly, cancer patients carrying different mutant variants of R273 in p53 have different survival rates, indicating that the DNA-contact inhibition may not be the sole reason for reduced survival with R273 variants.

Functional protein shells fabricated from the self-assembling protein sheets of prokaryotic organelles.

Fabricating protein compartments from protein units is challenging and limited by the use of external stimuli and crosslinkers. Here we explore the fabrication of all-protein compartments using self-assembled proteins of prokaryotic organelles. These proteins have intrinsic interacting domains which are ionic in nature, and spontaneously self-assemble into sheets when over-expressed.

Structural basis of the strong cell-cell junction formed by cadherin-23.

Cadherin-23, a giant atypical cadherin, forms homophilic interactions at the cell-cell junction of epithelial cells and heterophilic interactions with protocadherin-15 at the tip-links of neuroepithelial cells. While the molecular structure of the heterodimer is solved, the homodimer structure is yet to be resolved. The homodimers play an essential role in cell-cell adhesion as the downregulation of cadherin-23 in cancers loosen the intercellular junction resulting in faster-migration of cancer cells and a significant drop in patient survival.

Broken force dispersal network in tip-links by the mutations at the Ca-binding residues induces hearing-loss.

Tip-link as force-sensor in hearing conveys the mechanical force originating from sound to ion-channels while maintaining the integrity of the entire sensory assembly in the inner ear. This delicate balance between structure and function of tip-links is regulated by Ca-ions present in endolymph. Mutations at the Ca-binding sites of tip-links often lead to congenital deafness, sometimes syndromic defects impairing vision along with hearing.

Force-activated catalytic pathway accelerates bacterial adhesion against flow.

Mechanical cues often influence the factors affecting the transition states of catalytic reactions and alter the activation pathway. However, tracking the real-time dynamics of such activation pathways is limited. Using single-molecule trapping of reaction intermediates, we developed a method that enabled us to perform one reaction at one site and simultaneously study the real-time dynamics of the catalytic pathway.

LINCRNA00273 promotes cancer metastasis and its G-Quadruplex promoter can serve as a novel target to inhibit cancer invasiveness.

Discovery of anti-metastatic drugs is of immense clinical significance as metastasis is responsible for 90% of all cancer deaths. Here we report the inhibitory effect of a bis schiff base (M2) on cancer cell migration and invasion and . M2 has shown good solubility and permeability across the intestinal cell wall and hence can be classified as BCS (Biopharmaceutical classification system) class I.

Effect of Coelogyne cristata Lindley in alleviation of chronic fatigue syndrome in aged Wistar rats.

Background: Swarna Jibanti scientifically known as Coelogyne cristata Lindley (Orchidaceae), an orchid mentioned in Ayurvedic medicine is used to promote healthy life span.

Objective(s): The present work was planned to study the efficacy of hydro-alcoholic extract of pseudobulbs of C. cristata (CCE) to assess its role on chronic fatigue syndrome (CFS) induced behavioural and biochemical changes in aged Wistar rats compared to Panax ginseng (PG), a prototype anti-stress agent.

Symmetry and the geometric phase in ultracold hydrogen-exchange reactions.

Quantum reactive scattering calculations are reported for the ultracold hydrogen-exchange reaction and its non-reactive atom-exchange isotopic counterparts, proceeding from excited rotational states. It is shown that while the geometric phase (GP) does not necessarily control the reaction to all final states, one can always find final states where it does. For the isotopic counterpart reactions, these states can be used to make a measurement of the GP effect by separately measuring the even and odd symmetry contributions, which experimentally requires nuclear-spin final-state resolution.