Secretome Analysis of <i>Thermothelomyces thermophilus</i> LMBC 162 Cultivated with <i>Tamarindus indica</i> Seeds Reveals CAZymes for Degradation of Lignocellulosic Biomass

The analysis of the secretome allows us to identify the proteins, especially carbohydrate-active enzymes (CAZymes), secreted by different microorganisms cultivated under different conditions. The CAZymes are divided into five classes containing different protein families. Thermothelomyces thermophilus is a thermophilic ascomycete, a source of many glycoside hydrolases and oxidative enzymes that aid in the breakdown of lignocellulosic materials. The secretome analysis of T. thermophilus LMBC 162 cultivated with submerged fermentation using tamarind seeds as a carbon source revealed 79 proteins distributed between the five diverse classes of CAZymes: 5.55% auxiliary activity (AAs); 2.58% carbohydrate esterases (CEs); 20.58% polysaccharide lyases (PLs); and 71.29% glycoside hydrolases (GHs). In the identified GH families, 54.97% are cellulolytic, 16.27% are hemicellulolytic, and 0.05 are classified as other. Furthermore, 48.74% of CAZymes have carbohydrate-binding modules (CBMs). Observing the relative abundance, it is possible to state that only thirteen proteins comprise 92.19% of the identified proteins secreted and are probably the main proteins responsible for the efficient degradation of the bulk of the biomass: cellulose, hemicellulose, and pectin

A comparative test of theories of polarity and conflict

Works on the relationship between polarity and war in the past produce inconsistent, sometimes, self-conflicting conclusions. This is caused by the lack of a comparable way of conceptualizing and defining polarity and the lack of a common gauge for estimating that relationship. This research addresses these methodological shortcomings and explores the linkage between the international system of the major powers and dyadic conflict by conducting a comparative study of polarity and war. It tests the targeted relationship using: 1) a number of quantifiable polarity concepts proposed by several representative scholars, including John Mearsheimer, Jack Levy, Charles Kegley and Gregory Raymond, and George Modelski; 2) a common research design that has incorporated the Kantian variables and has drawn the essence from the latest progress in this discipline, and 3) an objective method of calculating a continuous measure of the polarity among the great powers. Such a research design can compare the impact of various types of polarity on the onset of wars while controlling for both realist and Kantian influences. It provides a broad prospective on the connection between polarity and war. This study confirms the existence of a connection between polarity and war of unipolarity > bipolarity > multipolarity in order of peacefulness. (Published By University of Alabama Libraries

Astrocytic Mechanisms Involving Kynurenic Acid Control Δ9-Tetrahydrocannabinol-Induced Increases in Glutamate Release in Brain Reward-Processing Areas

The reinforcing effects of Δ9-tetrahydrocannabinol (THC) in rats and monkeys, and the reinforcement-related dopamine-releasing effects of THC in rats, can be attenuated by increasing endogenous levels of kynurenic acid (KYNA) through systemic administration of the kynurenine 3-monooxygenase inhibitor, Ro 61-8048. KYNA is a negative allosteric modulator of α7 nicotinic acetylcholine receptors (α7nAChRs) and is synthesized and released by astroglia, which express functional α7nAChRs and cannabinoid CB1 receptors (CB1Rs). Here, we tested whether these presumed KYNA autoreceptors (α7nAChRs) and CB1Rs regulate glutamate release. We used in vivo microdialysis and electrophysiology in rats, RNAscope in situ hybridization in brain slices, and primary culture of rat cortical astrocytes. Acute systemic administration of THC increased extracellular levels of glutamate in the nucleus accumbens shell (NAcS), ventral tegmental area (VTA), and medial prefrontal cortex (mPFC). THC also reduced extracellular levels of KYNA in the NAcS. These THC effects were prevented by administration of Ro 61-8048 or the CB1R antagonist, rimonabant. THC increased the firing activity of glutamatergic pyramidal neurons projecting from the mPFC to the NAcS or to the VTA in vivo. These effects were averted by pretreatment with Ro 61-8048. In vitro, THC elicited glutamate release from cortical astrocytes (on which we demonstrated co-localization of the CB1Rs and α7nAChR mRNAs), and this effect was prevented by KYNA and rimonabant. These results suggest a key role of astrocytes in interactions between the endocannabinoid system, kynurenine pathway, and glutamatergic neurotransmission, with ramifications for the pathophysiology and treatment of psychiatric and neurodegenerative diseases

Dose imbalance of DYRK1A kinase causes systemic progeroid status in Down syndrome by increasing the un-repaired DNA damage and reducing LaminB1 levels

People with Down syndrome (DS) show clinical signs of accelerated ageing. Causative mechanisms remain unknown and hypotheses range from the (essentially untreatable) amplified-chromosomal-instability explanation, to potential actions of individual supernumerary chromosome-21 genes. The latter explanation could open a route to therapeutic amelioration if the specific over-acting genes could be identified and their action toned-down.Ministry of Education (MOE)Ministry of Health (MOH)Published versionThis work has been supported by the “Research Cooperability” Program of the Croatian Science Foundation funded by the European Union from the European Social Fund under the Operational Programme Efficient Human Resources 2014–2020, Project PZS-2019-02-4277 (to GL and DN). This work has been also supported in part by the European Structural and Investment funding for the ‘Croatian National Centre of Research Excellence in Personalized Healthcare’, contract #KK.01.1.1.01.0010 (to GL); ‘Centre of Competences in Molecular Diagnostics’, contract #KK.01.2.2.03.0006 (to GL); the European Regional Development Fund grant ‘CardioMetabolic’ agreement #KK.01.2.1.02.0321 (to GL). DN was also funded by the Singapore Ministry of Education Academic Research Fund Tier 2 grants (2015-T2- 1-023 & 2015-T2-2-119) and the Wellcome Trust Collaborative Award in Science 217199/Z/19/Z. The teams of AStr, MT and DN also received funding from the Wellcome Trust “LonDownS Consortium” Strategic Funding Award (098330/Z/12/Z) (UK). In addition, AStr was supported by funding from the MRC (Medical Research Council grants MRC S011277/1, MR/S005145/1 (from Centers of Excellence in Neurodegeneration research) and MR/R024901/1 (from JPND). This work was also supported by Waterloo Foundation and Baily Thomas Charitable Fund (to MT). AM was awarded a William Harvey Academy Fellowship, co-funded by the People Programme (Marie Curie Actions) under REA no. 608765. IA was awarded an Adris Foundation grant (251-61-01/139- 22-01). The work of doctoral student HD has been supported by the “Young researchers’ career development project—training of doctoral students” of the Croatian Science Foundation. DM was supported by the Croatian Science Foundation project Orastem (IP-16-6-9451) and the European Union through the European Regional Development Fund, as the Scientific Centre of Excellence for Basic, Clinical and Translational Neuroscience under Grant Agreement No. KK.01.1.1.01.0007. JNF received funding from the National Medical Research Council, Singapore (MOH-000559). SdlL received funding from a Spanish Ministry of Science and Innovation grant PID2019-107185GB-I00

Mental Health and Clinical Psychological Science in the Time of COVID-19: Challenges, Opportunities, and a Call to Action

COVID-19 presents significant social, economic, and medical challenges. Because COVID-19 has already begun to precipitate huge increases in mental health problems, clinical psychological science must assert a leadership role in guiding a national response to this secondary crisis. In this article, COVID-19 is conceptualized as a unique, compounding, multidimensional stressor that will create a vast need for intervention and necessitate new paradigms for mental health service delivery and training. Urgent challenge areas across developmental periods are discussed, followed by a review of psychological symptoms that likely will increase in prevalence and require innovative solutions in both science and practice. Implications for new research directions, clinical approaches, and policy issues are discussed to highlight the opportunities for clinical psychological science to emerge as an updated, contemporary field capable of addressing the burden of mental illness and distress in the wake of COVID-19 and beyond