EVALUATION OF ACUTE AND DERMAL TOXICITY OF ESSENTIAL OIL OF ETLINGERA FENZLII (KURZ) K. SCHUM: AN IN VIVO STUDY

Objective: The present investigation describes the in vivo acute toxicity and dermal toxicity of essential oil of Etlingera fenzlii (E. fenzlii) in Wistar albino rats.Methods: The essential oil was extracted by hydro-distillation using Clevenger apparatus. The acute toxicity study was conducted in Wistar albino rats at different doses (175,550 and 2000 mg/kg) while dermal toxicity study was carried out with simple ointment base and essential oil at a dose of 2000 mg/kg body weight. Animals were observed for 14 d and parameters like body weight, feed intake and water intake were studied.Results: No mortality and no significant changes were observed in body weight and wellness parameters at 175,550 and 2000 mg/kg body weight doses. Further, the dermal absorption with essential oil also did not reveal any treatment-related changes in body weight, food consumption and water intake in any of the animals tested.Conclusion: These findings suggest that the acute and dermal application of the essential oil of E. fenzlii in rats did not divulge any significant toxicity, and the oil extracts were found to be safe up to 2000 mg/kg in vivo concentration.Keywords: Etlingera fenzlii, Acute toxicity, Dermal toxicity, Median Lethal Dose (LD 50

A New Cyber Forensic Philosophy for Digital Watermarks in the Context of Copyright Laws

The objective of this paper is to propose a new cyber forensic philosophy for watermark in the context of copyright laws for the benefit of the forensic community and the judiciary worldwide. The paper first briefly introduces various types of watermarks, and then situates watermarks in the context of the ideaexpression dichotomy and the copyright laws. It then explains the forensic importance of watermarks and proposes a forensic philosophy for them in the context of copyright laws. Finally, the paper stresses the vital need to incorporate watermarks in the forensic tests to establish software copyright infringement and also urges the judiciary systems worldwide to study and legalize the evidential aspects of digital watermarks in the context of copyright laws. Keywords: Digital Watermarks, Software Copyright, Idea-Expression Dichotomy, Programming Blunders, Copyright Infringement, AFC, POSA

Optimization of Cutting Parameters for Cutting Force in Shoulder Milling of Al7075-T6 Using Response Surface Methodology and Genetic Algorithm

AbstractThis paper aims at developing a statistical model to predict cutting force in terms of machining parameters such as cutting speed, cutting feed rate and axial depth of cut. Response surface methodology experimental design was used for conducting experiments. The work piece material was Aluminum (Al 7075-T6) and the tool was a shoulder mill with two carbide insert. The cutting forces were measured using three axis milling tool dynamometer. The second order mathematical model in terms of machining parameters was developed for predicting cutting force. The adequacy of the predictive models was tested by analysis of variance and found to be adequate. The direct and interaction effect was graphically plotted which helps to study the significance of these parameters with cutting force. The optimization of shoulder mill machining parameters to acquire minimum cutting force was done by genetic algorithms (GA). A Matlab genetic algorithm solver was used to do the optimization

Efficacy studies on commercially available probiotics to induce immune response and resistance in tilapia fish (Oreochromis mossambicus), against Vibrio infection

1175-1183The current research was undertaken to determine the potency of two distinct probiotics Biogut® Aqua (feed probiotic) and Bioclean® Aqua (water and soil probiotic) to induce immunity and protection faced due to Vibrio pathogen during cultivation of Mozambique tilapia under controlled laboratory trials. Assessment was carried out using immune gene expression and immunological assays. During the initial phase of treatment, nitro blue tetrazolium (NBT) assay, antiprotease assay and peroxidase assay displayed a convincing raise in serum activity of the probiotic managed feed when compared to the control groups. In addition, qPCR real time analysis displayed in which nutritional implementation with feed probiotic vitally increased the interpretation of immune related genes, particularly TNF and MCP gene expression which are involved in immune response. The results revealed that the probiotics Bioclean® Aqua and Biogut® Aqua have beneficial effects through efficiently enhancing immune system and protection in tilapia model facing Vibriosis. Hence it can be stated that the application of probiotics like Biogut® Aqua and Bioclean® Aqua in aquaculture environment may significantly reduce the antibiotic usage, thereby preventing the entry of these chemicals into the food chain. Additionally it was demonstrated that the ammonia level in water can be reduced significantly with the application of Bioclean® Aqua (water and soil probiotic). The toxicity studies proved that both the probiotic are non-toxic and safe for the use in aquaculture environment

Stimuli-Responsive Properties of Supramolecular Gels Based on Pyridyl-N-oxide Amides

Publisher Copyright: © 2023 by the authors.The nature of functional groups and their relative position and orientation play an important role in tuning the gelation properties of stimuli-responsive supramolecular gels. In this work, we synthesized and characterized mono-/bis-pyridyl-N-oxide compounds of N-(4-pyridyl)nicotinamide (L 1–L 3). The gelation properties of these N-oxide compounds were compared with the reported isomeric counterpart mono-/bis-pyridyl-N-oxide compounds of N-(4-pyridyl)isonicotinamide. Hydrogels obtained with L 1 and L 3 were thermally and mechanically more stable than the corresponding isomeric counterparts. The surface morphology of the xerogels of di-N-oxides (L 3 and diNO) obtained from the water was studied using scanning electron microscopy (SEM), which revealed that the relative position of N-oxide moieties did not have a prominent effect on the gel morphology. The solid-state structural analysis was performed using single-crystal X-ray diffraction to understand the key mechanism in gel formation. The versatile nature of N-oxide moieties makes these gels highly responsive toward an external stimulus, and the stimuli-responsive behavior of the gels in water and aqueous mixtures was studied in the presence of various salts. We studied the effect of various salts on the gelation behavior of the hydrogels, and the results indicated that the salts could induce gelation in L 1 and L 3 below the minimum gelator concentration of the gelators. The mechanical properties were evaluated by rheological experiments, indicating that the modified compounds displayed enhanced gel strength in most cases. Interestingly, cadmium chloride formed supergelator at a very low concentration (0.7 wt% of L 3), and robust hydrogels were obtained at higher concentrations of L 3. These results show that the relative position of N-oxide moieties is crucial for the effective interaction of the gelator with salts/ions resulting in LMWGs with tunable properties.Peer reviewe

Effect of thermization of dahi on post fermentation acidification during refrigerated storage

Post fermentation acidification is defined as the development of acidity past the desired level of fermentation or acid development. Effect of thermization at 65oC for different periods (30 sec, 60 sec, 2 min and 5 min) on post fermentation acidification of dahi samples prepared using Lacticaseibacillus rhamnosus 18 or Lacticaseibacillus casei 01 upon refrigerated storage was assessed in this study. Significant changes (p< 0.01) were observed between the two starter cultures in terms of their post acidification potential with L. rhamnosus 18 dahi showing lower pH, higher titratable acidity and lactobacilli count than L. casei 01 during refrigerated storage. On assessing the impact of heat treatment on post acidification, significant decrease (p< 0.05) in pH, increase (p< 0.01) in titratable acidity and lactobacilli count of the heat treated and control samples were observed throughout the storage. Based on this study, it can be inferred that heat treatment at 65oC for even upto 5 min is not having any significant inhibitory effect on post fermentation acidification characteristics of the lactobacilli cultures tested

Gain control network conditions in early sensory coding

Gain control is essential for the proper function of any sensory system. However, the precise mechanisms for achieving effective gain control in the brain are unknown. Based on our understanding of the existence and strength of connections in the insect olfactory system, we analyze the conditions that lead to controlled gain in a randomly connected network of excitatory and inhibitory neurons. We consider two scenarios for the variation of input into the system. In the first case, the intensity of the sensory input controls the input currents to a fixed proportion of neurons of the excitatory and inhibitory populations. In the second case, increasing intensity of the sensory stimulus will both, recruit an increasing number of neurons that receive input and change the input current that they receive. Using a mean field approximation for the network activity we derive relationships between the parameters of the network that ensure that the overall level of activity of the excitatory population remains unchanged for increasing intensity of the external stimulation. We find that, first, the main parameters that regulate network gain are the probabilities of connections from the inhibitory population to the excitatory population and of the connections within the inhibitory population. Second, we show that strict gain control is not achievable in a random network in the second case, when the input recruits an increasing number of neurons. Finally, we confirm that the gain control conditions derived from the mean field approximation are valid in simulations of firing rate models and Hodgkin-Huxley conductance based models

Novel engineered nanobodies specific for N-terminal region of alpha-synuclein recognize Lewy-body pathology and inhibit in-vitro seeded aggregation and toxicity.

Nanobodies (Nbs), the single-domain antigen-binding fragments of dromedary heavy-chain antibodies (HCAb), are excellent candidates as therapeutic and diagnostic tools in synucleinopathies because of their small size, solubility and stability. Here, we constructed an immune nanobody library specific to the monomeric form of alpha-synuclein (α-syn). Phage display screening of the library allowed the identification of a nanobody, Nbα-syn01, specific for α-syn. Unlike previously developed nanobodies, Nbα-syn01 recognized the N-terminal region which is critical for in vitro and in vivo aggregation and contains many point mutations involved in early PD cases. The affinity of the monovalent Nbα-syn01 and the engineered bivalent format BivNbα-syn01 measured by isothermal titration calorimetry revealed unexpected results where Nbα-syn01 and its bivalent format recognized preferentially α-syn fibrils compared to the monomeric form. Nbα-syn01 and BivNbα-syn01 were also able to inhibit α-syn-seeded aggregation in vitro and reduced α-syn-seeded aggregation and toxicity in cells showing their potential to reduce α-syn pathology. Moreover, both nanobody formats were able to recognize Lewy-body pathology in human post-mortem brain tissue from PD and DLB cases. Additionally, we present evidence through structural docking that Nbα-syn01 binds the N-terminal region of the α-syn aggregated form. Overall, these results highlight the potential of Nbα-syn01 and BivNbα-syn01 in developing into a diagnostic or a therapeutic tool for PD and related disorders

Fibrillar form of α-synuclein-specific scFv antibody inhibits α-synuclein seeds induced aggregation and toxicity

Synucleinopathies including Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) are characterized by pathological accumulation of α-synuclein (α-syn). Amongst the various approaches attempting to tackle the pathological features of synucleinopathies, antibody-based immunotherapy holds much promise. However, the large size of antibodies and corresponding difficulty in crossing the blood-brain barrier has limited development in this area. To overcome this issue, we engineered single-chain variable fragments (scFvs) against fibrillar α-syn, a putative disease-relevant form of α-syn. The purified scFvs showed specific activity towards α-syn fibrils and oligomers in comparison to monomers and recognized intracellular inclusions in human post-mortem brain tissue of Lewy body disease cases, but not aged controls. In vitro studies indicated scFvs inhibit the seeding of α-syn aggregation in a time-dependent manner, decreased α-syn seed-induced toxicity in a cell model of PD, and reduced the production of insoluble α-syn phosphorylated at Ser-129 (pS129-α-syn). These results suggest that our α-syn fibril-specific scFvs recognize α-syn pathology and can inhibit the aggregation of α-syn in vitro and prevent seeding-dependent toxicity. Therefore, the scFvs described here have considerable potential to be utilized towards immunotherapy in synucleinopathies and may also have applications in ante-mortem imaging modalities.Dr. El-Agnaf’s laboratory was funded by Qatar Biomedical Research Institute under the Start-up Fund SF 2017– 007. The Newcastle Brain Tissue Resource is funded in part by a grant from the UK Medical Research Council, by NIHR Newcastle Biomedical Research Centre awarded to the Newcastle upon Tyne NHS Foundation Trust and Newcastle University, and by a grant from the Alzheimer’s Society and Alzheimer’s Research UK as part of the Brains for Dementia Research Project

Macrophages in Breast Cancer: Do Involution Macrophages Account for the Poor Prognosis of Pregnancy-Associated Breast Cancer?

Macrophage influx is associated with negative outcomes for women with breast cancer and has been demonstrated to be required for metastasis of mammary tumors in mouse models. Pregnancy-associated breast cancer is characterized by particularly poor outcomes, however the reasons remain obscure. Recently, post-pregnancy mammary involution has been characterized as having a wound healing signature. We have proposed the involution-hypothesis, which states that the wound healing microenvironment of the involuting gland is tumor promotional. Macrophage influx is one of the prominent features of the involuting gland, identifying the macrophage a potential instigator of tumor progression and a novel target for breast cancer treatment and prevention