"Learning in reverse: Dopamine errors drive excitatory and inhibitory components of backward conditioning in an outcome-specific manner".

For over two decades, midbrain dopamine was considered synonymous with the prediction error in temporal-difference reinforcement learning. Central to this proposal is the notion that reward-predictive stimuli become endowed with the scalar value of predicted rewards. When these cues are subsequently encountered, their predictive value is compared to the value of the actual reward received allowing for the calculation of prediction errors. Phasic firing of dopamine neurons was proposed to reflect this computation, facilitating the backpropagation of value from the predicted reward to the reward-predictive stimulus, thus reducing future prediction errors. There are two critical assumptions of this proposal: 1) that dopamine errors can only facilitate learning about scalar value and not more complex features of predicted rewards, and 2) that the dopamine signal can only be involved in anticipatory learning in which cues or actions precede rewards. Recent work has challenged the first assumption, demonstrating that phasic dopamine signals across species are involved in learning about more complex features of the predicted outcomes, in a manner that transcends this value computation. Here, we tested the validity of the second assumption. Specifically, we examined whether phasic midbrain dopamine activity would be necessary for backward conditioning- when a neutral cue reliably follows a rewarding outcome. Using a specific Pavlovian-to-Instrumental Transfer (PIT) procedure, we show rats learn both excitatory and inhibitory components of a backward association, and that this association entails knowledge of the specific identity of the reward and cue. We demonstrate that brief optogenetic inhibition of ventral tegmental area dopamine (VTA DA) neurons timed to the transition between the reward and cue, reduces both of these components of backward conditioning. These findings suggest VTA DA neurons are capable of facilitating associations between contiguously occurring events, regardless of the content of those events. We conclude that these data are in line with suggestions that the VTA DA error acts as a universal teaching signal. This may provide insight into why dopamine function has been implicated in a myriad of psychological disorders that are characterized by very distinct reinforcement-learning deficits.

ДОЦІЛЬНІСТЬ ЗАСТОСУВАННЯ СТЕРИЧНО УСКЛАДНЕНИХ АЦЕНАФТЕНОВИХ СПОЛУК У СКЛАДІ ПРОТИКОРОЗІЙНОЇ КОМПОЗИЦІЇ

Goal. Synthesis and study of the effect of the inhibitory component – sterically complicated acenaphthene compounds – on the effectiveness of the protective composition to prevent corrosion of metal products during the period of temporary preservation.Method. Coke-chemical acenaphthylene was isolated from the absorbing and anthracene fractions of coal tar, the bromination of which led to 1,2-dibromocenaphthene. Subsequent alkylation of azine bases with 1,2-dibromacenaphthene yielded a number of sterically complex acenaphthene compounds. In the conditions of simulation aggressiveness of NSS environment the influence of synthesized additives on efficiency of anticorrosive composition is investigated (ISO 9227:2017). Research methods: chromatography, synthesis, elemental analysis, IR spectroscopy, corrosion tests.Results. On the basis of low-demand, available and inexpensive components of coke production, a number of substances with high anti-corrosion properties were synthesized – Quaternary azine salts with acenaphthene fragment. It was determined that the greatest resistance to the destructive effects of corrosive NSS environment according to the results of accelerated atmospheric corrosion tests was demonstrated by a composite coating containing an inhibitory additive – 1-(2-bromo-1,2-dihydroacenaphthylen-1-yl) quinoline bromide. The dominant role of the structure of the inhibitory additive on the manifestation of anticorrosive properties of the protective composition is shown. The influence of the ratio of components of paints and varnishes on their technological and anti-corrosion properties has been studied. The obtained results allow to create a new formulation of the domestic competitive protective composition to prevent corrosion of the metal for the period of temporary preservation.Scientific novelty. The role of 1,2-dibromacenaphthene as a promising alkylating agent in the synthesis of inhibitory additives - sterically complicated acenaphthene compounds has been determined.Practical significance. The optimal content of inhibitory components – Quaternary azine salts with acenaphthene fragment – for the development of a formulation of an effective anti-corrosion composition for the period of temporary preservation of metal products.

Protective properties of mechanochemically fabricated zeolite/phosphate anticorrosion pigments for paint coatings

The anticorrosion environmentally friendly pigments based on synthetic zeolite and zinc and calcium phosphates were prepared by mechanochemical method. The surface morphology and chemical composition of the obtained pigments were determined by scanning electron microscopy and energy-dispersive X-ray spectroscopy, respectively. It was established that the modification of zeolite by phosphates of divalent metals causes a decrease in the particle size and an increase in the specific surface area of the obtained composite pigments. It was shown that the use of zeolite/phosphate pigments increases the corrosion resistance of the aluminium alloy in 0.1% aqueous NaCl solution. The addition of complex zeolite/phosphate pigments to the sodium chloride solution decelerates the anodic process of electrochemical corrosion, which indicates the formation of a protective film on the metal surface. The composite pigment zeolite/Zn(H2PO4)2 exhibited the highest anticorrosive effect. A gradual release of the inhibitory components from these environmentally friendly pigments provides their long-term action to protect metal products.

Interactions between the land snails Theba pisana and Cernuella virgata in the laboratory

ABSTRACT Two Mediterranean snails, Theba pisana and Cernuella virgata, are agricultural pests in southern Australia. The two species are rarely found together in large numbers in the field, at small scales (<1 m2). In laboratory experiments, the presence of T. pisana reduced the survival of C. virgata, but only when food (carrot + lettuce) was provided. When C. virgata was exposed to only the mucus trails and faeces of T. pisana, produced while feeding on lettuce, both the survival and activity of C. virgata were reduced. When carrot was substituted for lettuce, there was less effect. In addition, when C. virgata was exposed to T. pisana’s faeces only, derived from access to a mix of lettuce and carrot, there was no effect on C. virgata’s survival. The observed reductions in the survival of C. virgata were stronger in autumn (the breeding season for both snail species) compared with spring. Inhibitory components within the mucus trails of T. pisana may (1) help explain the observed distribution patterns of the two species at small scales in the field and (2) provide a novel method for control of pest populations of C. virgata, in some situations.

Potential benefits of dietary seaweeds as protection against COVID-19

The coronavirus disease 2019 (COVID-19) pandemic in Japan is not as disastrous as it is in other Western countries, possibly because of certain lifestyle factors. One such factor might be the seaweed-rich diet commonly consumed in Japan. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which binds to angiotensin-converting enzyme 2 (ACE2) on the cell surface and downregulates ACE2, likely elevating the ratio of angiotensin-converting enzyme (ACE) to ACE2. The overreaction of the immune system, combined with the cytokine storm and ACE dominance, is purported to cause the condition of COVID-19 patients to deteriorate rapidly. Dietary seaweeds contain numerous components, including ACE inhibitory peptides, soluble dietary fibers (eg, fucoidan, porphyran), omega-3 fatty acids, fucoxanthin, fucosterol, vitamins D3 and B12, and phlorotannins. These components exert antioxidant, anti-inflammatory, and antiviral effects directly as well as indirectly through prebiotic effects. It is possible that ACE inhibitory components could minimize the ACE dominance caused by SARS-CoV-2 infection. Thus, dietary seaweeds might confer protection against COVID-19 through multiple mechanisms. Overconsumption of seaweeds should be avoided, however, as seaweeds contain high levels of iodine.

CSF Levels of the Endocannabinoid Anandamide are Reduced in Patients with Untreated Narcolepsy Type 1: A Pilot Study

Background : Endocannabinoids (ECs) modulate both excitatory and inhibitory components in the CNS. There is a growing body of evidence that shows ECs influence both hypothalamic orexinergic and histaminergic neurons involved in narcolepsy physiopathology. Therefore, ECs may influence sleep and sleep-wake cycle. Objective : To evaluate EC levels in the CSF of untreated narcoleptic patients to test whether ECs are dysregulated in Narcolepsy Type 1 (NT1) and Type 2 (NT2). Methods : We compared CSF Anandamide (AEA), 2-Arachidonoylglycerol (2-AG) and orexin in narcoleptic drug-naïve patients and in a sample of healthy subjects. Results : We compared NT1 (n=6), NT2 (n=6), and healthy controls (n=6). We found significantly reduced AEA levels in NT1 patients compared to both NT2 and controls. No differences were found between AEA levels in NT2 versus controls and between 2-AG levels in all groups, although a trend toward a decrease in NT1 was evident. Finally, the CSF AEA level was related to CSF orexin levels in all subjects. Conclusion : We demonstrated that the EC system is dysregulated in NT1.

Testing the transdiagnostic hypothesis of inhibitory control deficits in addictions: An experimental study on gambling disorder

Background and aimsMany psychopathologies, including addictions, are characterized by inhibitory control deficits. In this regard, recent studies on substance-related disorders (SRD) have shown an impairment in the ability to inhibit potentially interfering memories, despite preserved motor inhibition. To investigate whether the same dissociation could also characterize gambling disorder (GD) in a transdiagnostic perspective, we tested both cognitive and motor inhibitory processes through dedicated tasks, for the first time in this behavioral addiction.Methods30 outpatients with GD and 30 healthy controls performed a go/no-go task addressing the integrity of motor inhibition, and the Retrieval Practice Paradigm, a task addressing the integrity of memory inhibition as indexed by the Retrieval-Induced Forgetting (RIF) effect. Self-report questionnaires assessing impulsivity were also administered.ResultsWhereas RIF was similar across the two groups, patients showed more commission errors in the go/no-go task, and higher self-rated scores of impulsivity than controls.DiscussionThe present findings suggest preserved memory inhibition and impaired motor response inhibition in GD, a pattern of inhibitory deficits opposite to that previously reported for SRD. Therefore, although both GD and SRD are characterized by altered inhibitory processing, a more fine-grained analysis revealed a specific inhibitory profile indicating vulnerability in different inhibitory components.ConclusionThe present study highlights the need to investigate the multifaceted construct of inhibition more thoroughly, using performance measures able to assess its various components. This approach would enable to both better characterize different psychopathologies and orient their treatment.

Serum proteomics in COVID-19 patients: Altered coagulation and complement status as a function of IL-6 level

Over 5 million people around the world have tested positive for the beta coronavirus SARS-CoV-2 as of May 29, 2020, a third of which in the United States alone. These infections are associated with the development of a disease known as COVID-19, which is characterized by several symptoms, including persistent dry cough, shortness of breath, chills, muscle pain, headache, loss of taste or smell, and gastrointestinal distress. COVID-19 has been characterized by elevated mortality (over 100 thousand people have already died in the US alone), mostly due to thromboinflammatory complications that impair lung perfusion and systemic oxygenation in the most severe cases. While the levels of pro-inflammatory cytokines such as interleukin-6 (IL-6) have been associated with the severity of the disease, little is known about the impact of IL-6 levels on the proteome of COVID-19 patients. The present study provides the first proteomics analysis of sera from COVID-19 patients, stratified by circulating levels of IL-6, and correlated to markers of inflammation and renal function. As a function of IL-6 levels, we identified significant dysregulation in serum levels of various coagulation factors, accompanied by increased levels of anti-fibrinolytic components, including several serine protease inhibitors (SERPINs). These were accompanied by up-regulation of the complement cascade and antimicrobial enzymes, especially in subjects with the highest levels of IL-6, which is consistent with an exacerbation of the acute phase response in these subjects. Although our results are observational, they highlight a clear increase in the levels of inhibitory components of the fibrinolytic cascade in severe COVID-19 disease, providing potential clues related to the etiology of coagulopathic complications in COVID-19 and paving the way for potential therapeutic interventions, such as the use of pro-fibrinolytic agents.

Development of an Effective Two-Step Enrichment Process to Enhance Bax System Detection of Healthy and Injured Salmonella Enteritidis in Liquid Whole Egg and Egg Yolk

ABSTRACT The BAX system for pathogen detection has been highly accurate in a variety of food products. However, false-negative results have been reported for the detection of pathogens in liquid egg products because of failed pathogen resuscitation and the existence of inhibitory components. In this study, a short-time enrichment step was used to simultaneously resuscitate the target cells to the detection level and to dilute the inhibitory components to reduce detection interference. The MP medium (BAX system) enabled faster multiplication of healthy Salmonella cells than did buffered peptone water (BPW) in tested liquid whole egg and egg yolk. However, MP failed to resuscitate heat-injured cells even after 24 h of incubation. Therefore, MP was replaced with BPW as the enrichment broth for the BAX system. However, the use of BPW for a one-step enrichment was not effective for removal of PCR inhibitors in egg yolk, and unstable detection results were obtained. To improve detection accuracy, a second step of enrichment with brain heart infusion was added. This two-step enrichment process shortened the enrichment time to 14 h and greatly increased the number of samples in which the pathogen was detected during the same enrichment time, especially in the liquid egg yolk samples. The validation study revealed 100% diagnostic accuracy of the two-step enrichment process plus the BAX system. These results indicate that a two-step enrichment process added to the BAX system can improve the detection of pathogenic Salmonella in liquid egg products. HIGHLIGHTS

Chemical Analysis (GC-FID-MS) and Antimicrobial Activity of Parmotrema perlatum Essential Oil Against Clinical Specimens

The major study of this work was to evaluate the chemical composition and the inhibitory components of Parmotrema perlatum against the clinically isolated specimens of Staphylococcus, Streptococcus, Escherichia, Pseudomonas and Candida.. The GC-FID-MS by using a Trace GC Ultra apparatus MS DSQ II detectors and FID-MS splitter under the operating conditions of apolar capillary column was employed to determine the chemical composition of Parmotrema perlatum essential oil. Amino acid (38.1%) and cymene (29.1%) were the most adequate constituents in this oil. The antibacterial activity of Parmotrema perlatum oil was tested against standard strains of bacteria and clinical strains isolated from patients with infections of the oral cavity, abdominal cavity, respiratory, genitourinary tracts, skin, and from the hospital environment. Kirby-Bauer disc diffusion technique was employed to determine the susceptibility of the organism towards the Parmotrema perlatum essential oil exhibited very strong antimicrobial activity to inhibit the growth of the clinical specimens. Application of natural antimicrobial based essential oil from Parmotrema perlatum can be potential source in the treatment & prevention of different types of infections as an alternative to the chemical - based antibiotics based on the investigation.