Interplay between Affect and Arousal in Recognition Memory

Background

Emotional states linked to arousal and mood are known to affect the efficiency of cognitive performance. However, the extent to which memory processes may be affected by arousal, mood or their interaction is poorly understood.

Methodology/Principal Findings

Following a study phase of abstract shapes, we altered the emotional state of participants by means of exposure to music that varied in both mood and arousal dimensions, leading to four different emotional states: (i) positive mood-high arousal; (ii) positive mood-low arousal; (iii) negative mood-high arousal; (iv) negative mood-low arousal. Following the emotional induction, participants performed a memory recognition test. Critically, there was an interaction between mood and arousal on recognition performance. Memory was enhanced in the positive mood-high arousal and in the negative mood-low arousal states, relative to the other emotional conditions.

Conclusions/Significance

Neither mood nor arousal alone but their interaction appears most critical to understanding the emotional enhancement of memory.     

Identification and characterization of a leucine-rich repeat kinase 2 (LRRK2) consensus phosphorylation motif

Mutations in LRRK2 (leucine-rich repeat kinase 2) have been identified as major genetic determinants of Parkinson's disease (PD). The most prevalent mutation, G2019S, increases LRRK2's kinase activity, therefore understanding the sites and substrates that LRRK2 phosphorylates is critical to understanding its role in disease aetiology. Since the physiological substrates of this kinase are unknown, we set out to reveal potential targets of LRRK2 G2019S by identifying its favored phosphorylation motif. A non-biased screen of an oriented peptide library elucidated F/Y-x-T-x-R/K as the core dependent substrate sequence. Bioinformatic analysis of the consensus phosphorylation motif identified several novel candidate substrates that potentially function in neuronal pathophysiology. Peptides corresponding to the most PD relevant proteins were efficiently phosphorylated by LRRK2 in vitro. Interestingly, the phosphomotif was also identified within LRRK2 itself. Autophosphorylation was detected by mass spectrometry and biochemical means at the only F-x-T-x-R site (Thr 1410) within LRRK2. The relevance of this site was assessed by measuring effects of mutations on autophosphorylation, kinase activity, GTP binding, GTP hydrolysis, and LRRK2 multimerization. These studies indicate that modification of Thr1410 subtly regulates GTP hydrolysis by LRRK2, but with minimal effects on other parameters measured. Together the identification of LRRK2's phosphorylation consensus motif, and the functional consequences of its phosphorylation, provide insights into downstream LRRK2-signaling pathways.     

Biotransformation of aromatic and heterocyclic amides by amidase of whole cells of Rhodococcus sp. MTB5: Biocatalytic characterization and substrate specificity

In this study, an amidohydrolase activity of amidase in whole cells of Rhodococcus sp. MTB5 has been used for the biotransformation of aromatic, monoheterocyclic and diheterocyclic amides to corresponding carboxylic acids. Benzoic acid, nicotinic acid and pyrazinoic acid are carboxylic acids which have wide industrial applications. The amidase of this strain is found to be inducible in nature. The biocatalytic conditions for amidase present in the whole cells of MTB5 were optimized against benzamide. The enzyme exhibited optimum activity in 50?mM potassium phosphate buffer pH 7.0. The optimum temperature and substrate concentrations for this enzyme were 50?°C and 50?mM, respectively. The enzyme was quite stable for more than 6?h at 30?°C. It showed substrate specificity against different amides, including aliphatic, aromatic and heterocyclic amides. Under optimized reaction conditions, the amidase is capable of converting 50?mM each of benzamide, nicotinamide and pyrazinamide to corresponding acids within 100, 160 and 120?min, respectively, using 5?mg dry cell mass (DCM) per mL of reaction mixture. The respective percent conversion of these amides was 95.02%, 98.00% and 98.44% achieved by whole cells. The amidase in whole cells can withstand as high as 383?mM concentration of product in a reaction mixture and above which it undergoes product feedback inhibition. The results of this study suggest that Rhodococcus sp. MTB5 amidase has the potential for large-scale production of carboxylic acids of industrial value.     

Structural and energetic profiling of SARS-CoV-2 receptor binding domain antibody recognition and the impact of circulating variants

The SARS-CoV-2 pandemic highlights the need for a detailed molecular understanding of protective antibody responses. This is underscored by the emergence and spread of SARS-CoV-2 variants, including Alpha (B.1.1.7) and Delta (B.1.617.2), some of which appear to be less effectively targeted by current monoclonal antibodies and vaccines. Here we report a high resolution and comprehensive map of antibody recognition of the SARS-CoV-2 spike receptor binding domain (RBD), which is the target of most neutralizing antibodies, using computational structural analysis. With a dataset of nonredundant experimentally determined antibody-RBD structures, we classified antibodies by RBD residue binding determinants using unsupervised clustering. We also identified the energetic and conservation features of epitope residues and assessed the capacity of viral variant mutations to disrupt antibody recognition, revealing sets of antibodies predicted to effectively target recently described viral variants. This detailed structure-based reference of antibody RBD recognition signatures can inform therapeutic and vaccine design strategies.     

Binding to syntenin-1 protein defines a new mode of ubiquitin-based interactions regulated by phosphorylation

Syntenin-1 is a PDZ domain-containing adaptor that controls trafficking of transmembrane proteins including those associated with tetraspanin-enriched microdomains. We describe the interaction of syntenin-1 with ubiquitin through a novel binding site spanning the C terminus of ubiquitin, centered on Arg(72), Leu(73), and Arg(74). A conserved LYPSL sequence in the N terminus, as well as the C-terminal region of syntenin-1, are essential for binding to ubiquitin. We present evidence for the regulation of this interaction through syntenin-1 dimerization. We have also established that syntenin-1 is phosphorylated downstream of Ulk1, a serine/threonine kinase that plays a critical role in autophagy and regulates endocytic trafficking. Importantly, Ulk1-dependent phosphorylation of Ser(6) in the LYPSL prevents the interaction of syntenin-1 with ubiquitin. These results define an unprecedented ubiquitin-dependent pathway involving syntenin-1 that is regulated by Ulk1.     

Metabolic Characterization of cold active Pseudomonas, Arthrobacter, Bacillus, and Flavobacterium spp. from Western Himalayas

Himalayan soils undergo dramatic temporal changes in their microclimatic properties. The soil habitats in the high altitude cold habitats of Himalayas are little explored with respect to bacterial diversity and metabolic potentials of the bacterial species. Soil habitat in Western Himalayas is dominated by the genera of Pseudomonas, Arthrobacter, Bacillus, and Flavobacterium. Strains were found to be diverse in their metabolic potentials to utilize different carbon sources by growing them on media containing 114 different sole carbon sources. Bacillus sp. STL9 was supported by the lowest number (12.3%) of the carbon sources while growth was observed in 73.7% of the carbon sources tested for the Pseudomonas sp. SPS2. Carbohydrates appeared to be preferred carbon sources for these Himalayan isolates followed by amino acids and proteins. These microbes also produced various extra-cellular hydrolytic enzymes having biotechnological potentials, lipase being the one secreted by most strains (85.7%) followed by β-galactosidase (42.8%). Antibiotic resistance profiling for 85 different antibiotics has also been described.     

Rediscovery of Lichen Genus Psorotheciopsis Rehm for India

The genus Psorotheciopsis Rehm recorded by Cunningham from Calcutta in 1879 has been rediscovered for India after a gap of 135 years. The taxonomic characters of Psorotheciopsis patellarioides (Rehm) Rolf Santesson are provided to facilitate the identification of the species. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)