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The embodiment of consciousness in socio-cognitive agents play a significant role in their acceptance as co-partners. Man-machine social interaction’s success is based on the agent’s generated believable behaviors. In this regard, such an agent needs to generate realistic beliefs, intentions, goals, self-regulation, verbal, and non-verbal communication (including gestures) according to the context of ongoing interaction is very important. This study hypothesizes that the implementation of the Theory of mind (TOM) may allow the agent to change its intentions, beliefs, and desires by predicting the existing perspective and mental states of the other agents involved in the given social interaction. To study the complexity of dynamics in a social context we have taken the case study of the ‘paper-scissor-rock’ game and developed a cognitive agent capable of using gestures for non-verbal communication following the Theory of mind. This work is in progress and is being developed on the iCub robot simulation. We have used tapped delay line neural networks as the basis for reinforcement learning and strategic planning. This paper will report the cognitive model, neural network initial results obtained.

Sarcoptes scabiei is a causative organism for scabies that affects an estimated global population of 300 million and remains a disease of significant concern. Recently, a number of potential drug targets were identified for scabies, including hydrolytic enzymes, inactivated paralogues of hydrolytic enzymes, inhibitors of host proteolytic enzymes and other proteins of interest. These discoveries remain confined to academic laboratories and institutions, failing to attract interest from researchers in commercial drug development. Here, we summarize the latest developments in the scabies mite biology and the drug targets that were subsequently identified, and we propose several peptide and nonpeptide ligands targeting the hot spots for protein–protein interactions. We also identify gaps in the development of ligands as inhibitors or modulators of these macromolecules.

Learning and memory are among the executive functions attributed to intelligent forms of life. Unfortunately, there is a lack of clear understanding regarding the underlying mechanisms governing these functions. Most of the modern day scientists attribute these functions solely to brain. However, in the latter half of last century, a number of reports suggested existence of extra-cranial memory and potential of its transfer between animals. Some have linked this phenomenon to RNA while others believed that peptides were responsible. The terms like "educated RNA" and "scotophobin" were coined. This atypical work involving flatworms, yeast RNA and scotophobin was received with deep skepticism and ultimately disregarded. However, the recent reproduction of some of this earlier work by scientists at Tufts University has reignited the debate on the mechanisms of learning and memory. Keeping this in view, we believe it is high time to summarize this historical work and discuss the possibilities to delineate these atypical claims. The objective is to incite the present day researchers to explore this opportunity under the perspective of newer advancements in science.

Background Diabetic neuropathy is the most prevalent, persistent and debilitating complication of diabetes mellitus often coupled with vulvodynia that may present as an isolated symptom or as a part of constellation of other neuropathic abnormalities. Objective Flavonoids have selective affinity for GABA receptors and 6-methoxyflavanone (6-MeOF) is a positive allosteric modulator of GABA responses at human recombinant GABAA receptors. GABAergic and opioidergic system inhibition have been shown to facilitate neuropathic pain. Methods 6-MeOF was evaluated for analgesic effect in the hot plate test and streptozotocin-induced diabetic neuropathic pain in female rats using von Frey hairs. The possible involvement of opioidergic and GABAergic mechanisms was investigated using naloxone and pentylenetetrazole (PTZ) antagonists, respectively. The biodistribution of 6-MeOF in plasma and CNS was examined using a validated HPLC/UV analytical method. The binding affinity of 6-MeOF with opioid and GABA receptors was studied using molecular docking simulation approach. Results 6-MeOF (10 and 30 mg/kg) attenuated the acute phasic thermal nociception in the hot plate test while in the case of streptozotocin-induced diabetic neuropathy model, 6-MeOF (10 and 30 mg/kg) produced static/dynamic anti-allodynic (increased paw withdrawal threshold and latency) as well as static/dynamic anti-vulvodynic effects (increased flinching response threshold and latency), when compared to the vehicle and standard gabapentin (75 mg/kg). In silico studies depicted the preference of 6-MeOF for the delta- and kappa-opioid and GABAA receptors. Moreover, the pharmacokinetic profile revealed a quick appearance of 6-MeOF in the systemic circulation and brain areas with maximum concentration observed after 30 min in the amygdala, brain stem and cerebral cortex. Conclusion 6-MeOF readily crosses the blood brain barrier and may be effective in attenuating the diabetes-induced allodynia as well as vulvodynia, probably through interactions with the GABAergic and opioidergic systems.

β-glucan (polysaccharide) rich diet has been reported to enhance cognition in humans but the mechanism remained elusive. Keeping this in mind, the present study was designed to investigate the interaction of β-glucan with central cholinergic system. Briefly, in-silico analysis revealed promising interactions of β-glucan with the catalytic residues of acetylcholinesterase (AChE) enzyme. In line with this outcome, the in vitro assay (Ellman's method) also exhibited inhibition of AChE by β-glucan (IC50=0.68±0.08μg/µl). Furthermore, the in vivo study (Morris water maze) showed significant dose dependent reversal of the amnesic effect of scopolamine (2mg/kg i.p.) by β-glucan treatment (5, 25, 50 and 100mg/kg, i.p.). Finally, the hippocampi of aforementioned treated animals also revealed dose dependent inhibition of AChE enzyme. Hence, it can be deduced that β-glucan possesses potential to enhance central cholinergic tone via inhibiting AChE enzyme. In conclusion, the present study provides mechanistic insight to the cognition enhancing potential of β-glucan. Keeping in mind its dietary use and abundance in nature, it can be considered as economic therapeutic option against cognitive ailments associated with decline in cholinergic neurotransmission.

Despite their possible causative role, targeting amyloidosis, tau phosphorylation, acetylcholine esterase, glutamate, oxidative stress and mitochondrial metabolism have not yet led to the development of drugs to cure Alzheimer’s disease (AD). Recent preclinical and clinical reports exhibit a surge in interest in the role of GABAergic neurotransmission in the pathogenesis of AD. The interaction among GABAergic signaling, amyloid-β and acetylcholine is shown to affect the homeostasis between excitation (glutamate) and inhibition (GABA) in the brain. As a consequence, over-excitation leads to neurodegeneration (excitotoxicity) and impairment in the higher level functions. Previously, the glutamate arm of this balance received the most attention. Recent literature suggests that over-excitation is primarily mediated by dysfunctional GABA signaling and can possibly be restored by rectifying anomalous metabolism observed in the GABAergic neurons during AD. Additionally, neurogenesis and synaptogenesis have also been linked with GABAergic signaling. This association may provide a basis for the needed repair mechanism. Furthermore, several preclinical interventional studies revealed that targeting various GABA receptor subtypes holds potential in overcoming the memory deficits associated with AD. In conclusion, the recent scientific literature suggests that GABAergic signaling presents itself as a promising target for anti-AD drug development.

The book covers a variety of topics in Information and Communications Technology (ICT) and their impact on innovation and business. The authors discuss various innovations, business and industrial motivations, and impact on humans and the interplay between those factors in terms of finance, demand, and competition. Topics discussed include the convergence of Machine to Machine (M2M), Internet of Things (IoT), Social, and Big Data. They also discuss AI and its integration into technologies from machine learning, predictive analytics, security software, to intelligent agents, and many more. Contributions come from academics and professionals around the world. Covers the most recent practices in ICT related topics pertaining to technological growth, innovation, and business; Presents a survey on the most recent technological areas revolutionizing how humans communicate and interact; Features four sections: IoT, Wireless Ad Hoc & Sensor Networks, Fog Computing, and Big Data Analytics. (Chapter) The recent advancements in robotic systems set new challenges for robotic simulation software, particularly for planning. It requires the realistic behavior of the robots and the objects in the simulation environment by incorporating their dynamics. Furthermore, it requires the capability of reasoning about the action effects. To cope with these challenges, this study proposes an open-source simulation tool for knowledge-oriented physics-based motion planning by extending The Kautham Project, a C++ based open-source simulation tool for motion planning. The proposed simulation tool provides a flexible way to incorporate the physics, knowledge and reasoning in planning process. Moreover, it provides ROS-based interface to handle the manipulation actions (such as push/pull) and an easy way to communicate with the real robots

Alendronate sodium, a bisphosphonate drug, it is used to treat osteoporosis and other bone diseases. The present study was designed to conduct comparative bioavailability analysis of oral formulations of aledronate sodium through an open-label, randomized, 2-sequence, 2-period crossover study. Healthy adult male Pakistani volunteers received a single 70 mg dose of the test or reference formulation of alendronate sodium followed by a 7 day washout period. Plasma drug concentrations were determined using a validated HPLC post column fluorescence derivatization method. AUC(01,) AUC(0-8,) C(max). and T(max) were determined by non-compartmental analysis and were found within the permitted range of 80% to 125% set by the US Food and Drug Administration (FDA). Results show that both in vitio and in vivo assays of all test brands were within the spec- ification of the US Pharmacopoeial limits and were statistically bioequivalent. No adverse events were reported in this study.

This article reports microbial biotransformation of dexamethasone, a synthetic glucocorticoid, by Bacillus subtilis. This bacterium can be used as a microbial metabolic model to investigate the metabolism of other synthetic glucocorticoids as it mimics mammalian metabolism to a certain extent. Incubation of dexamethasone with B. subtilis for 7 days yielded three compounds identified as 6-hydroxydexamethasone, 17-oxodexamethasone, and 6-hydroxy-17-oxodexamethasone. Structure elucidation of these compounds was done using 1H-NMR and 13C-NMR spectroscopy techniques.

Repeated low doses of alcohol have been shown to progressively enhance locomotor activity in mice, and this phenomenon is designated as behavioral sensitization. Thymoquinone, a major active component of Nigella sativa oil has been investigated in a number of studies for its neuroprotective effects against a variety of ailments. This study was conducted to explore the therapeutic potential of thymoquinone on the acquisition and expression of alcohol-induced behavioral sensitization. Mice treated with alcohol (2.2 g/kg/day) or saline for 13 days and subsequently challenged with an acute alcohol dose (2.2 g/kg) 5 days later were orally administered acute doses of thymoquinone (10, 20 and 30 mg/kg). Thymoquinone subacute treatment with all doses throughout alcohol exposure significantly inhibited both the development and expression phases of alcohol behavioral sensitization in a dose-dependent manner. However, acute treatment with thymoquinone (30 mg/kg) only reversed the expression phase of sensitization. These findings are explained in terms of the known GABA promoting action of thymoquinone in relation to the motive circuit within the limbic component of the basal ganglia. It is concluded that thymoquinone may be a potential therapeutic option for the treatment and prevention of alcohol induced behavioral sensitization.

A two way, randomized cross-over bioequivalence study was conducted to analyse the rate and extent of absorption of atorvastatin after a single dose of 80 mg atorvastatin as atorvastatin calcium tablets. The study was carried out using healthy male volunteers (N = 24). A high performance liquid chromatography method was employed to determine the level of drug in human plasma. It was concluded that the test and the reference drug exhibited comparable values of pharmacokinetic parameters. It was also concluded that since there was no significant difference between the rate and extent of absorption of the drug from the test and the reference formulations: these two formulations could thus be declared bioequivalent.

The current study was aimed at investigating the total antioxidant activity (TAC) of various fruits, vegetables, herbs and spices habitat in Pakistan. The ferric reducing ability of plasma (FRAP) assay was used to measure the TAC of various extracts (aqueous, ethanolic and aqueous-ethanolic). Following is the potency order for fruits (guavastrawberryPomegranateapplekinnowmelonlemonbanana), vegetables (spinachCabbage (Purple)JalapenoRadishBrinjalBell PepperLettuceCarrotCabbage (White)OnionPotatoTomatoCucumber) and herbs/spices (cloveRosemaryThymeOreganoCinnamonCuminKalonjiPaprikaNeem (Flower)FennelBlack CardamomTurmericCorianderGingerGarlic). In conclusion, the guava, spinach and clove provide the best natural dietary option for treatment / prevention of oxidative stress and thus could alleviate several associated ailments.

Structural transformation of ezetimibe was performed by fungi Beauvaria bassiana and Cunninghamella blakesleeana. The metabolites were identified by different spectroscopic techniques as (3R,4S)-1-(4-fluorophenyl)-3-((E)-3-(4-fluorophenyl) allyl)-4-(4-hydroxyphenyl) azetidin-2-one (2), (3R, 4S)-1-(4-fluorophenyl)-3-(3-(4fluorophenyl)-3-oxopropyl)-4-(4-hydroxyphenyl) azetidin-2-one (3), (3R,4S) 1-(4-fluorophenyl)-3-(3-(4-fluorophenyl) propyl)-4-(4-hydroxyphenyl) azetidin-2-one (4) and (2R,5S)-N, 5-bis (4-fluorophenyl)-5-hydroxy-2-(4-hydroxybenzyl) pentanamide (5). This study displays two important features of these fungi, viz., their ability to metabolize halogenated compounds, and their capacity to metabolize drugs that are targets of the UDP-Glucuronyl Transferase System, a phenomenon not commonly observed.

Among arthropod pests, mites are responsible for considerable damage to crops, humans and other animals. However, detailed physiological data on these organisms remain sparse, mainly because of their small size but possibly also because of their extreme diversity. Focusing on intestinal proteases, we draw together information from three distinct mite species that all feed on skin but have separately adapted to a free-living, a strictly ecto-parasitic and a parasitic lifestyle. A wide range of studies involving immunohistology, molecular biology, X-ray crystallography and enzyme biochemistry of mite gut proteases suggests that these creatures have diverged considerably as house dust mites, sheep scab mites and scabies mites. Each species has evolved a particular variation of a presumably ancestral repertoire of digestive enzymes that have become specifically adapted to their individual environmental requirements.

Purpose: To synthesize and characterize novel hydroquinone compounds that exhibit an aspirin-like pharmacological profile devoid of ulcerogenic side effects.Methods: Two novel hydroquinone derivatives, viz, 2,5-bis(piperidinomethyl)hydroquinone and 2,5- bis(pyrrolidinomet hyl)hydroquinone, were synthesized by refluxing hydroquinone, paraformaldehyde and secondary amines (piperidine or pyrrolidine) in ethanol. The structures were authenticated by infrared (IR) spectroscopy, elemental analysis, mass spectrometry (MS) and 1H and 13C nuclear magnetic resonance (NMR) spectroscopic techniques. The synthesized derivatives were evaluated for antinociceptive, anti-inflammatory and antipyretic activities along with gastric-ulcerogenicity using wellknown testing paradigms. Aspirin served as reference standard.Results: The newly synthesized hydroquinone derivatives, significantly attenuated tonic visceral chemically-induced nociception at 10 mg/kg (p < 0.01, p < 0.001), 20 and 40 mg/kg (p < 0.001), inhibited the temporal-inflammatory reaction at 50 mg/kg (2 - 5 h, p < 0.05, p < 0.001), 100 and 150 mg/kg (1 - 5 h, p < 0.05, p < 0.01, p < 0.001) in addition to alleviating the febrile-response at test doses during 0.5 h (p < 0.05, p < 0.01, p < 0.001), 1 and 1.5 h (p < 0.001) of the study period. The synthesized compounds exhibited improved gastric tolerability profile since they were devoid of aspirin-associated biochemical and ulcerative changes. The in silico studies predicted high binding affinity of the hydroquinone derivatives to the active site of the cyclooxygenase 2 (COX-2) enzyme.Conclusion: The synthesized hydroquinone compounds possess analgesic, antipyretic and antiinflammatory properties with low gastric-ulcerogenic potential. This may be credited to preferential inhibition of the COX-2 enzyme and the beneficial basic rather than acidic chemical nature of the compounds. However, further molecular studies are required to substantiate these findings.Keywords: 2,5-Bis(piperidinomethyl)hydroquinone], 2,5- is(pyrrolidinomethyl)hydroquinone, Antiinflammatory, Antinociceptive, Antipyretic, Gastric-ulcerogenicity, Algesia

The aim of the study was to explore the traditional use of Cinnamomum cassia against depression. The standardised methanolic extract of the bark of C. cassia was evaluated for antidepressant activity using various behavioural tests, i.e. tail suspension test (TST), forced swim test (FST) and locomotor activity test. The serotonergic and noradrenergic modulation was assessed using 5-hydroxytryptophan (5-HTP)-induced head twitches and yohimbine potentiation tests, respectively. The fluoxetine and phenelzine were used as positive controls in the study. The C. cassia extract significantly decreased the immobility time in TST (maximum effective dose tested was 50 mg/kg) while no effect was observed in FST and locomotor activity test. The extract significantly increased the 5-HTP-induced head twitches while yohimbine-induced lethality remained unaltered. The aforementioned results are similar to that caused by fluoxetine. The standardised methanolic extract of C. cassia demonstrated antidepressant activity that can be attributed to rise in serotonin levels.

Depression is on the rise globally and expected to lead in global burden of diseases by 2030. The current therapy has serious limitations in terms of safety, efficacy, tolerability and therapeutic success. This review, based on the literature of the last decade, is aimed at exploring the preclinical profile of plant-based saponins (the abundant secondary metabolite) as an emerging therapy for depression. Enough scientific evidences reflect that saponins promote neurogenesis, restore monoaminergic tone and enhance neurotrophic factors. In multiple stress models, they have exhibited adaptogenic effects via normalising hypothalamus-pituitary-adrenal axis, corticosterone levels and oxidative stress. Scientific data revealed neuroprotective effect of saponins by inhibiting apoptosis and intraneuronal calcium dynamics. Many plants possessing saponins as their principal antidepressant moiety need investigation at clinical level. Last decade literature revealed numerous preclinical reports supporting the role of saponins as natural cure for depression and justified their inclusion in antidepressant drug discovery programs.

A small series of 2-(hetero(aryl)methylene) hydrazine-1-carbothioamides including two aryl derivatives was synthesized and tested for their inhibitory activity against urease. Compound (E)-2-(Furan-2-ylmethylene) hydrazine-1-carbothioamide (3f), having a furan ring, was the most potent inhibitor of urease with an IC50 value of 0.58 μM. Molecular modeling was carried out through docking the designed compounds into the urease binding site to predict whether these derivatives have analogous binding mode to the urease inhibitors. The study revealed that all of the tested compounds bind with both metal atoms at the active site of the enzyme. The aromatic ring of the compounds forms ionic interactions with the residues, Ala(440), Asp(494), Ala(636), and Met(637).

Background Scabies is a disease of worldwide significance, causing considerable morbidity in both humans and other animals. The scabies mite Sarcoptes scabiei burrows into the skin of its host, obtaining nutrition from host skin and blood. Aspartic proteases mediate a range of diverse and essential physiological functions such as tissue invasion and migration, digestion, moulting and reproduction in a number of parasitic organisms. We investigated whether aspartic proteases may play role in scabies mite digestive processes. Methodology/Principle Findings We demonstrated the presence of aspartic protease activity in whole scabies mite extract. We then identified a scabies mite aspartic protease gene sequence and produced recombinant active enzyme. The recombinant scabies mite aspartic protease was capable of digesting human haemoglobin, serum albumin, fibrinogen and fibronectin, but not collagen III or laminin. This is consistent with the location of the scabies mites in the upper epidermis of human skin. Conclusions/Significance The development of novel therapeutics for scabies is of increasing importance given the evidence of emerging resistance to current treatments. We have shown that a scabies mite aspartic protease plays a role in the digestion of host skin and serum molecules, raising the possibility that interference with the function of the enzyme may impact on mite survival., Author Summary Scabies is an infectious disease of the skin caused by infestation with the parasitic mite Sarcoptes scabiei. It is a disease that has a considerable impact on humans and other animals, including livestock, wildlife and companion animals. Scabies mites burrow into the skin of their host, consuming host skin and blood molecules. Aspartic proteases play a key role in invasion and digestion processes in many parasitic organisms. We have identified a scabies mite aspartic protease and have shown that it is capable of digesting human haemoglobin, serum albumin, fibrinogen and fibronectin in vitro, indicating that it plays a role in mite digestive processes. This raises the possibility that interfering with the function of this digestive enzyme may impact on mite survival.