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Dietary fibers are a major source of short-chain fatty acids (SCFAs) in the body, and the fermentation products of SCFAs induced by intestinal microbiota affect energy metabolism. Apart from serving as an energy source in the intestines, SCFAs also inhibit autophagy, nucleotide-binding oligomerization domain-containing protein, LRR, and pyrin domain-containing protein 3 inflammasome. SCFAs provide numerous therapeutic benefits through their influence on cognitive functioning and neurodegenerative diseases (NDD) pathophysiology. Additionally, NDDs are associated with abnormalities in the gut microbiota, including an increased load of pathogens and opportunistic microbes. SCFAs maintain the healthy mitochondrial function and stimulate the maturation of microglia, which consequently suppresses the progression of NDD and cognitive decline by regulating inflammation and oxidative stress. Basically, SCFAs function as cofactors for the host's mitochondrial enzymes and are being studied for their ability to reverse the alteration in the gut microbiota seen in many NDDs and cardiac diseases. In the present review, the focus is on the detrimental and beneficial roles of SCFAs in NDD, emphasizing the effects of SCFA on following phenomenon: (1) alteration in gut microbiota profile associated with NDD, (2) the molecular mechanism of metabolic regulation by SCFA's, and its co-relation with NDD, (3) use of mitochondrial antioxidants as a strategy for maintaining microbiota diversity in the gut, and (4) the future direction of metabolism and neurodegeneration in the gut-brain axis. In addition, the interplay between gut microbiota, SCFAs, epithelial barrier, and neuroimmune signaling in neurodegeneration has been reviewed.

Rationale: Currently, there is no effective intervention available that can reduce brain damage following reperfusion. Clinical studies suggest a positive correlation between the increased influx of neutrophils and severity of brain injury following reperfusion. Integrin α9β1 is highly expressed on activated neutrophils and contributes to stable adhesion, but its role in stroke outcome has not been demonstrated to date. Objective: We sought to determine the mechanistic role of myeloid-specific α9β1 in the progression of ischemic stroke in murine models with preexisting comorbidities. Methods and Results: We generated novel myeloid-specific α9-deficient ( α9 −/− ) wild type ( α9 fl/fl LysMCre +/− ), hyperlipidemic ( α9 fl/fl LysMCre +/− Apoe −/− ), and aged (bone marrow chimeric) mice to evaluate stroke outcome. Susceptibility to ischemia/reperfusion injury was evaluated at 1, 7, and 28 days following reperfusion in 2 models of experimental stroke: filament and embolic. We found that peripheral neutrophils displayed elevated α9 expression following stroke. Irrespective of sex, genetic deletion of α9 in myeloid cells improved short- and long-term stroke outcomes in the wild type, hyperlipidemic, and aged mice. Improved stroke outcome and enhanced survival in myeloid-specific α9 −/− mice was because of marked decrease in cerebral thromboinflammatory response as evidenced by reduced fibrin, platelet thrombi, neutrophil, NETosis, and decreased phospho-NF-κB (nuclear factor-κB), TNF (tumor necrosis factor)-α, and IL (interleukin)-1β levels. α9 −/− mice were less susceptible to FeCl 3 injury-induced carotid artery thrombosis that was concomitant with improved regional cerebral blood flow following stroke as revealed by laser speckle imaging. Mechanistically, fibronectin containing extra domain A, a ligand for integrin α9, partially contributed to α9-mediated stroke exacerbation. Infusion of a specific anti-integrin α9 inhibitor into hyperlipidemic mice following reperfusion significantly reduced infarct volume and improved short- and long-term functional outcomes up to 28 days. Conclusions: We provide genetic and pharmacological evidence for the first time that targeting myeloid-specific integrin α9β1 improves short- and long-term functional outcomes in stroke models with preexisting comorbidities by limiting cerebral thrombosis and inflammation.

This paper presents autonomous landing controller design of unmanned aerial vehicles (UAVs). Feedback linearization approach with anti windup scheme is designed as autonomous landing controller. Anti windup basically controls the integrator component accumulation in the autopilot design and restricts the output within saturation limits. Autonomous landing of a fixed wing UAV consists of approach, glideslope and flare phases. During approach, aerial vehicle aligns itself with runway and reduces its lateral deviations with respect to runway central line. In glide slope phase, aerial vehicle maintains a fixed flight path angle and descends with a constant sink rate. In flare phase, aerial vehicle follows an exponential trajectory and descends with a lower sink rate which keeps reducing further as it goes to lower altitudes. Flare controller is designed with integrator and antiwindup scheme is used to handle the controller output within saturation limits. Landing is primarily a longitudinal mode operation but due to disturbances and coupling lateral and directional modes also gets activated. In this paper pitch angle, roll angle and yaw angle nonlinear dynamic equations are linearized to obtain the control commands in terms of elevator deflection, aileron deflection and rudder deflections. Similarly total velocity of aerial vehicle being an important parameter is controlled using thrust command. A first order linearized model of velocity is used to obtain thrust control command. Autonomous landing of UAV with feedback linearization controller and anti windup scheme is simulated with Six-DOF model of AE2 UAV. The algorithm is implemented with wind disturbances to show the autonomous landing performance of UAV.

Autonomous landing of unmanned aerial vehicle with capability to avoid reactive collision using a mixed guidance scheme, which is a combination of ‘geometric optimization technique’ and ‘collision cone approach’ has been presented in this paper. Geometric optimization technique ensures minimal deviation from nominal trajectory to achieve optimal velocity, heading and elevation. Collision cone approach predicts collision ahead of time and provides aiming point for vehicle towards conflict resolution. A sobolev norm based robust neuro adaptive controller is designed to control the autonomous landing of vehicle with capability to avoid reactive collision under unknown external disturbances. A multilayer feed-forward network is designed based on radial basis function to estimate the unknown disturbances by fast learning. The autonomous landing vehicle senses the other UAV approaching towards it through its on board stereo vision sensing and performs a collision avoidance manoeuvre if the minimum predicted separation between UAVs is less than a predefined safety threshold distance. Both vehicles are simulated with a full fledged six degree of freedom model of a real vehicle.

Symphyotrichum squamatum (Spreng.) G.L.Nesom, is an erect herb of the Compositae family, recorded from the campus of the Shiv Nadar University, Uttar Pradesh, India. The species is being recorded for the first time from India as there are no earlier reports of its occurrence in the literature. The taxonomic description of the plant along with colored illustrations of morphological characteristics such as habit, leaf, flower, root etc. are provided for easy identification of the species in wild. As the plant is known to have a tendency to spread rapidly, it may become an aggressive weed in India in near future.

According to a recent statistical report from the American Heart Association (AHA), stroke is the fifth major reason for mortality and morbidity. Stroke is a devastating clinical condition for which efficient interventions are not currently available. The rodent stroke model has critical significance in a series of preclinical tests for neuroprotection, neurotransmitters, and neuroplasticity studies. Despite using animal modeling in neuroprotective research, their modeling, development, and preclinical evaluation of animals have been rarely and consistently demonstrated. Comorbidities like aging, diabetes, hypertension, and smoking are major contributors to stroke and the use of comorbid rodent models of stroke is clinically relevant to the human disease condition. Animals, like hypertensive rats and diabetic mice, these comorbid models, are used to explore the pathophysiology of cerebral stroke. Regional cerebral blood flow (rCBF) real-time tracking of arterial blood flow by using laser Doppler flowmetry (LDF) provide evidence for the success of middle cerebral artery (MCA) occlusion. Several factors play an important role in neurological outcomes, while have not happened before effectively addressed in Stroke Therapy Academic Industry Roundtable (STAIR) recommendations. Here, we describe the general guiding principle for a preclinical stroke model, STAIR committee recommendation, the procedure to develop intraluminal Middle Cerebral Artery Occlusion (MCAO) in rodent, surgical procedure optimization, MCA occluders like silicone-rubber coated, nylon coated, nail-polish coated, methyl methacrylate coated, poly-L-Lysine (PLL) coated and resin-coated and their physical properties. Besides, we will provide information on neurobehavior assessment, neuroprotection by volatile anesthesia molecule (halothane, isoflurane, desflurane, sevoflurane, and ketamine/xylazine cocktail), hypothermia induced neuroprotection, and hyperthermia damaging effect on ischemic injury.

Monitoring and performing agricultural practices over a large spatial coverage often require advanced and accurate positional information in order to optimize the operational costs as well as reduce estimated time of completion. Agricultural practices with large farms are challenging to operate from remote sensing until accurate positional information is not available, which necessitates the use of Global Positioning System (GPS) for acquiring sample position using Global Navigation Satellite System (GNSSs). Thus, development of positional accuracies with the help of GNSS signals has boosted up the involvement of GPS-based instruments in precision agriculture (PA). It has opened the wide door for the implementation of GPS in the PA, as per user needs and requirements. Furthermore, GPS instruments have been evolved with time, and nowadays advanced GPS instruments are in the market and can be operated via mobile with any operating systems, i.e., iOS, Android, or Windows. Availability of GPS signals in several instruments or equipment has been looked as the market opportunity and increasing trends in PA resulting in innovations of techniques for route optimization for optimal use of fertilizer spray and related activities in agricultural practices transforming to new look as SMART farming. The main conclusion of this chapter is to make aware about the growing GPS applications and evolution of SMART farming, that is, wisely employing Internet for precision applications.

Hybrid derivatives are a fascinating and challenging process in the area of drug discovery. Naphthalimide derivatives with modified norfloxacin moiety were designed and synthesized. Docking simulations were done to assess the interactions of the derivatives with the E. coli type II topoisomerases Gyrase B and ParE ATP-binding pocket by taking novobiocin as a standard molecule. Results suggested that the norfloxacin substituted naphthalimide derivatives indicate red-shift emission maxima when compared to 4-bromo 1,8-naphthalic anhydride. The molecular docking simulation study revealed that the derivatives have similar interaction but a different mode of binding with the gyrase B ATP-binding pocket as compare to novobiocin. However, they bound to ParE ATP-binding pocket similarly to novobiocin. The antibacterial property was confirmed with disc diffusion method. Our study indicated that the norfloxacin substituted naphthalimide novel derivatives have pronounced fluorescence, anti-topoisomerase activity, and antibacterial properties; therefore, they could be developed into new drug candidates.

Auto landing of unmanned aerial vehicles with reactive collision avoidance is presented in this paper. Unmanned aerial vehicle follows approach phase, glide slope phase and flare phases during auto landing maneuver. This auto landing unmanned aerial vehicle encounters another unmanned aerial vehicle which comes across its glide path and poses a threat of possible collision. The other vehicle is termed as an ‘obstacle’ for the auto landing vehicle. The prediction logic is used to compute the minimum distance between two vehicles. If the minimum predicted distance is less than a predefined safety distance then the possible collision is predicted. The collision cone based approach is used to compute the aiming point. The velocity vector is deflected using guidance strategies to reach the aiming point. The differential geometric guidance is used to reach the aiming point in the available time to go. The auto landing vehicle senses the obstacle approaching towards it through stereo vision sensing and performs a collision avoidance maneuver. During collision avoidance maneuver, auto landing vehicle changes its speed as well as direction. However, the speed reduction is subjected to stall speed of the vehicle. The non cooperative scenario is considered where only the auto landing vehicle performs the collision avoidance and the obstacle follows its nominal path. The cooperative scenario is also considered where both the vehicles perform collision avoidance maneuver and rejoin their respective path post collision avoidance maneuver. The six degree of freedom model of both the unmanned aerial vehicles is used for simulation.

Cerebral stroke is a major cause of death and physical disability throughout the world, yet therapeutic options remain limited. The outcomes of stroke injury are critical, causing an extensive burden to both the individual patient and society. Current interventions for stroke injury have been demonstrated to be inadequate, mostly attributable to a lack of understanding of the cellular and molecular changes that occur following an ischemic cerebral stroke. MicroRNAs (miRNAs) are small, endogenous, noncoding RNA molecules that have capacity as post-transcriptional negative regulators of a target mRNA by base-pairing with the 3′- untranslated region (3′-UTR). Novel methodologies are being produced to get miRNA-related therapeutics into the brain over an intact BBB, including chemical modification, use of targeting molecules and methods of disrupting the BBB. However, circulating miRNAs are novel, stable, and potential biomarkers for the early diagnosis of acute stroke in humans. These miRNA profiles also indicate the severity of stroke results related to age and sex in rodents. In this chapter, we focus on the pathophysiological role of miRNAs as novel diagnostic and prognostic biomarkers, in addition to promising therapeutic interventions in cerebral stroke patients.

Blood-brain barrier (BBB) is highly ultra-synchronized, structural and biochemical barrier between the peripheral blood circulation and the central nervous system (CNS) coordinate entry of blood-borne entities into the CNS. BBB anatomy is comprised of microvascular endothelium, pericytes, astrocytes and neuronal cells that constitute a neurovascular unit (NVU), participating a crucial role in proper functioning of the CNS. Every cell of NVU forms an indispensable contribution to BBB integrity. BBB functions are mainly controlled by tight and adherens junctional (TJ and AJ) protein complexes. These restrictive angioarchitectures at BBB reduce the paracellular diffusion of molecules, whereas carrier proteins determine which substance can cross the transcellular barrier. Under normal condition, BBB prevents extravasation of blood-borne cell, solute, ions and molecules. However, its disruption can lead to change in paracellular and transcellular permeability and extravasation of leukocytes into brain tissue, contributing oedema formation in neuropathological disorder including brain stroke. This chapter emphasized recently gained information on BBB anatomy and its neuropathogenetic alteration in an ischemic cerebral injury.

Interest in the clinical utilization of the magnetic field is increasing globally. Various articles have suggested the use of magnetic fields to initiate neuroprotective and neuro-regenerative effects on different biological systems that are of critical importance for the treatment of various injuries. Electromagnetic therapy provides a secure method for the direct treatment of injuries. The magnetic field may cause cell proliferation, genotoxic effects, changes in cell membrane permeability, and osteoblast formation. Some studies focus on the application of magnetic fields with different frequency bands and its corresponding effects at a cellular level. It has recently found that the static magnetic field (SMF) and the pulsating magnetic field (PEMF) can enhance the therapeutic outcome owing to anti-inflammatory and neuro-regenerative effects in animals and humans. In this chapter, we have included various mechanisms for neuroprotection and many experimental pieces of evidence to support the hypothesis that magnetic fields might constitute a non-invasive mode of therapy. Meanwhile, some of the experimental studies demonstrate the occurrence of protection, and various other articles propose that magnetic fields influence biochemical systems.

Stroke is the fifth leading cause of death and physical disability in the USA. Its prevention, diagnosis, and interventions are for the most part up and coming fields that give us feeling of how far medical and scientific work have progressed. Intravenous thrombolysis (IT) and endovascular thrombectomy (EVT) are evidence-based treatments for adults with a blocked blood vessel (ischemic stroke). EVT intervention is better than tpA treatment because of faster recanalization and less risk of hemorrhage especially in large artery occlusions. EVT treatment options include: Catheter-directed thrombolysis (CDT), pharmacomechanical catheter-directed thrombolysis (PCDT), percutaneous aspiration thrombectomy (PAT), vena cava filter protection, venous balloon dilatation and venous stent implantation. The feasibility, safety, and outcome of all therapies need to be assessed in adults, children, and pregnant women who have had a stroke. The significance of neuroprotective investigations in murine and stroke patients should be deliberately checked. Stem cells, nanoformulations and electromagnetic fields (EMF) are helpful emerging therapeutic interventions that contribute to the treatment of stroke patients.

Stroke is still a leading cause of death and physical disability among adults. For stroke patients, there is a need for improved and effective therapy. Tissue plasminogen activator is a single FDA-approved drug available for treatment with short window of opportunity (it must be applied within 4.5 h of symptom onset). Over the years, several clinical trials of potential drugs have failed to show positive results. Stem cell therapy currently holds great promise as a neuroregenerative medical strategy for stroke by replenishing the lost brain functions. In the clinical arena of stroke therapy, animal studies revealed that the therapeutic efficacy of stem cells, including mesenchymal stem cells, neural stem cells, embryonic stem cells, and inducible pluripotent stem cells, may be due to angiogenesis, endogenous neurogenesis, neurorestoration, neuroprotection, and modulation of inflammation and immune responses. In this chapter, the current status, therapeutic potential, and the detailed factors of stem cell-based therapy for ischemic stroke are presented and discussed.

This paper presents the applications of $L_{1}$ adaptive controller for autonomous landing of small unmanned aerial vehicles (UAVs) and for tracking the reference commands. Since small UAVs have lower mass and moment of inertia, they are very susceptible to external disturbances such as wind and gust forces. Small UAVs stability and performance can also be affected due to the parameter uncertainty in their system dynamics. This requires that the controller for the UAVs should be designed to track the reference trajectory even with parameter uncertainty in the system. The $L_{1}$ adaptive controller tracks a reference trajectory computed from any standard controller or any path planning algorithm under undisturbed plant or model with normal environment conditions. The controller takes into account the disturbances and computes the adaptive control command which enables the output reference tracking closer to the desired reference trajectory. The unknown disturbance is assumed constant and an adaptive law is used to estimate the unknown disturbance. Once the unknown disturbance is estimated the adaptive control law is computed considering the estimated disturbance and nullifies the effect of disturbance. The algorithm is implemented to show the autonomous landing performance on a longitudinal model with ground effect and parameter uncertainties.

Piscidin-1 possesses significant antimicrobial and cytotoxic activities. To recognize the primary amino acid sequence(s) in piscidin-1 that could be important for its biological activity, a long heptad repeat sequence located in the region from amino acids 2 to 19 was identified. To comprehend the possible role of this motif, six analogs of piscidin-1 were designed by selectively replacing a single isoleucine residue at a d (5th) position or at an a (9th or 16th) position with either an alanine or a valine residue. Two more analogs, namely, I5F,F6A-piscidin-1 and V12I-piscidin-1, were designed for investigating the effect of interchanging an alanine residue at a d position with an adjacent phenylalanine residue and replacing a valine residue with an isoleucine residue at another d position of the heptad repeat of piscidin-1, respectively. Single alanine-substituted analogs exhibited significantly reduced cytotoxicity against mammalian cells compared with that of piscidin-1 but appreciably retained the antibacterial and antiendotoxin activities of piscidin-1. All the single valine-substituted piscidin-1 analogs and I5F,F6A-piscidin-1 showed cytotoxicity greater than that of the corresponding alanine-substituted analogs, antibacterial activity marginally greater than or similar to that of the corresponding alanine-substituted analogs, and also antiendotoxin activity superior to that of the corresponding alanine-substituted analogs. Interestingly, among these peptides, V12I-piscidin-1 showed the highest cytotoxicity and antibacterial and antiendotoxin activities. Lipopolysaccharide (12 mg/kg of body weight)-treated mice, further treated with I16A-piscidin-1, the piscidin-1 analog with the highest therapeutic index, at a single dose of 1 or 2 mg/kg of body weight, showed 80 and 100% survival, respectively. Structural and functional characterization of these peptides revealed the basis of their biological activity and demonstrated that nontoxic piscidin-1 analogs with significant antimicrobial and antiendotoxin activities can be designed by incorporating single alanine substitutions in the piscidin-1 heptad repeat.

An effective reactive collision avoidance algorithm is presented in this paper for unmanned aerial vehicles (UAVs) using two simple inexpensive pinhole cameras. The vision sensed data, which consists of the azimuth and elevation angles at the two camera positions, is first processed through a Kalman filter formulation to estimate the position and velocity of the obstacle. Once the obstacle position is estimated, the collision cone philosophy is used to predict the collision over a short period of time. In case a collision is predicted, steering guidance commands are issued to the vehicle to steer its velocity vector away using the nonlinear differential geometric guidance. A new cubic spline based post-avoidance merging algorithm is also presented so that the vehicle rejoins the intended global path quickly in a smooth manner after avoiding the obstacle. The overall algorithm has been validated using the point mass model of a prototype UAV with first-order autopilot delay. Both extended Kalman filtering (EKF) and unscented Kalman filtering (UKF) have been experimented. Both are found to be quite effective. However, performance of UKF was found to be better than EKF with minor compromise in computational efficiency and hence it can be a better choice. Note that because of two cameras, stereovision signature gets associated with optical flow signature thereby making the overall signature quite strong for obstacle position estimation. This leads to a good amount of success as compared to the usage of a single pinhole camera, results of which has been published earlier.

This paper presents the autonomous landing performance of UAVs using Tracking-Model Predictive Static Programming(T-MPSP) guidance and dynamic inversion autopilot. T-MPSP guidance uses state constraint and control deviation across the landing trajectory and optimizes the control requirement in the outer loop whereas the dynamic inversion technique is implemented in the inner loop control computation. The landing phase is divided into approach, glideslope and flare. Approach is considered as a circular trajectory as well as a straight line level flying phase. Glideslope and flare are ramp with a constant flight path angle and exponential trajectories respectively. T-MPSP technique uses a suitable control guess history computed from a standard reference for its first iteration and then provides correction in the guess history in the successive iterations and updates the control law until tracking reaches closer to the desired output. The control command with T-MPSP algorithm is computed at grid points across the trajectory. A sliding window approach is implemented in T-MPSP to compute the control wherein once the control is computed at a grid point the window slides forward. The nonlinear Six-DOF aerodynamic model of AE2 UAV have been used for validation. (C) 2015, IFAC International Federation of Automatic Control) Hosting by Elsevier Ltd. All rights reserved.

Vision based autolanding of a fixed wing unmanned aerial vehicle (UAV) is presented in this paper. The UAV initially searches for a nearby unknown road or runway from the terrain image frames captured by onboard stereovision camera. The captured unknown road or runway are evaluated to be a possible candidate for autolanding of a UAV. Six degree of freedom ( $6DOF$ ) simulink model of a UAV with landing and navigation autopilot is integrated with flightgear flight simulation software. Flightgear FG camera is used to capture image frames of the nearyby terrain while UAV is in auto navigation mode and performing a level flight with various heading angles to look out for all possible terrain scenario. Image processing techniques are applied on the captured video to identify a smooth and straight road or runway for landing and calculates the relative distance and orientation of the runway or road with respect to UAV's own location. Image processing techniques such as hough transform and random Sample consensus (RANSAC) are used to detect the road strip lines. Once the desired touchdown point on the road is computed as well as road heading is also computed, UAV begins the autolanding maneuver. The image processing techniques are used to identify the candidate road or runway. The heading of the runway and cross track of the runway is computed and autopilot is designed to bring the aircraft at desired touch down point on the road or runway.

S016-1271 (LR8P) is a broad spectrum novel cationic antimicrobial peptide. The objective of the present study was to develop a selective liquid chromatography–tandem mass spectrometry (LC–MS/MS) based bioanalytical method of S016-1271 peptide in mice and human plasma in order to uncover its pharmacokinetic aspects. The chromatographic separation of S016-1271 (FR8P as internal standard) was achieved on a Waters™ X select CSH-C18 column (75 × 3.0 mm, 2.5 μ) using mixture of acetonitrile and triple distilled water (TDW) both containing 0.05% formic acid as mobile phase. A seven minute linear gradient method was designed to separate analytes from ion suppression at a flow rate of 0.3 mL/min. The extraction of analytes from mice and human plasma was performed through solid phase extraction technique using mixed mode weak cation exchange cartridge (Thermo SOLA WCX 10 mg 1CC) with an extraction recovery of analytes about 75%. Mass spectrometric detection of S016-1271 and FR8P was performed with optimized multiple reaction monitoring (MRM) transitions (Q1/Q3) at 658.8 [M+3H] 3+/653.2 [M+3H-NH3] 3+ and 443.4 [M+5H]5+ /434.7 [y12-NH3]4+,respectively in positive electrospray ionization (ESI) mode. The linearity in mice and human plasma was established over a concentration range of 7.81–250 ng/mL with regression coefficient (r2 > 0.99). The currently developed method was validated as per US-FDA guidelines and found to be within the acceptable limits. The method was successfully applied to intravenous (IV) pharmacokinetic study in mice wherein the levels were detected upto 24 h. The peptide demonstrated poor distribution characteristics which were demonstrated through volume of distribution at steady state (202.71 ± 47.02 mL/kg less than total body water of mice; 580 mL/kg). The clearance of the peptide predominantly occurred through central compartment (central clearance is 25 fold greater than peripheral clearance). Also, the in vitro pharmacokinetic studies demonstrated the stability of S016-1271 in plasma and high plasma protein binding in mice and humans.

The human skin remains under constant exposure of solar radiation and is vulnerable to epigenetic modifications that later may develop skin cancer. The effects of chronic UVR exposure to skin can alter epigenetic information in epidermal cells, leading to epigenetic mosaicism. These epigenetic changes include DNA methylation, chromatin modifications, and posttranscriptional modifications of noncoding RNAs. UVR-induced epigenetic changes are not irreversible. Certain phytochemicals can potentially inhibit cancer signaling pathways which are usually deregulated by epigenetic mechanisms. Indeed, recent therapeutic strategies are directing toward phytochemical-based reversal of epigenetic modifications to combat UVR-induced skin cancers. This chapter provides detailed insights of different epigenetic alterations, their role in photocarcinogenesis, and phytochemical-based reversal of epigenetic changes occurring in UVR-irradiated skin.

Radiant energy of sun is essential to perform metabolic processes of all flora and fauna on the earth. The electromagnetic radiations (EMR) emitted by sun extend from very long wavelength radiation, such as radiowaves (A ″′ 3 × 108 m), to very short wavelength radiation, such as cosmic rays (A ″′ 3 × 10−19 m). The EMR reaching at the earth surface contains wavelength from 290 to 4000 nm. However, the UV portion covers from 200 to 400 nm. The range from 200 to 400 nm is often arbitrarily categorized into UVA, UVB, and UVC radiation. Solar radiation less than 290 nm does not reach at the earth’s surface due to the presence of O3 layer in stratospheric zone. But, last from few decades due to anthropogenic activities, the concentration of ozone layer decreases on stratospheric zone. As a consequence of that, UVB radiation levels are rising to 1% a year. Thus, the deleterious health effects on human beings (skin aging, cataracts, skin cancer, and immune suppression) are enhanced by UVR.

HIV-1 transmission and spread involves significant host–virus interaction. Possible targets for obstacle of HIV-1 lie at the site of mucosal barriers. Thus a better understanding of how HIV-1 infects target cells at such sites and leads their invasion is required, with prime focus on the host determinants regulating HIV-1 spread. For the viral infectivity and pathogenicity, HIV-1 Nef facilitates immune evasion through protein–protein interactions within host cell. HIV-1 Nef is significant for viral infectivity and pathogenicity. It enhances HIV-1 replication, facilitating immune evasion by interacting with various host factors and altering cellular pathways via multiple protein–protein interactions. In this study, HIV-1 Nef forms with specific mutations, revealing sequence variability, were studied for their effects in human SupT1 T cell line and (THP-1) monocyte–macrophage cell line. Proteins being downregulated by Nef in SupT1 were further observed in THP-1, and interestingly two host proteins’ (ENO-1 and VDAC1) expression was found to be cell lineage specific, being stimulatory in macrophages/monocytes and inhibitory in T cells. Cell migration, invasion and ADP release studies were employed to determine the biological function affected by Nef-mediated regulation of these two host proteins. ENO1-regulated function: cell invasion was enhanced in THP-1 cells, but was inhibited in SupT1 cells by Nef RP01. In addition, the modulation of proteins and cell invasion remained unaffected by a Nef RP14. These results indicated that regulation of host protein expression and invasive property of host cells by Nef was sequence specific, suggesting involvement of a particular motif of Nef. To precisely determine this site, we designed a heptapeptide including the CAWLEAQ-regulating sequence of Nef. Macrophages/monocytes being the major cells affected by HIV-1 at mucosal barriers were particularly investigated by the peptide. The peptide led to reversal of differential expressions of ENO1 in both SupT1 and THP-1 and inhibition of enhanced invasiveness in THP-1 cells. Further AP-1 was identified as a factor involved in this Nef-mediated regulation of host proteins. Together these findings suggest a possible mechanism of host invasion by HIV-1 through the CAWLEAQ motif of Nef-mediated regulation of ENO1 and identify a potential therapeutic target for HIV-1 entry at mucosal barriers.

MD2, a 160-residue accessory glycoprotein, is responsible for the recognition and binding of Gram-negative bacterial membrane component, lipopolysaccharide (LPS). Internalization of pathogen inside the mononuclear phagocytes has also been attributed to MD2 which leads to the clearance of pathogens from the host. However, not much is known about the segments in MD2 that are responsible for LPS interaction or internalization of pathogen inside the defense cells. A 16-residue stretch (MD54) from MD2 protein has been identified that possesses a short heptad repeat sequence and four cationic residues enabling it to participate in both hydrophobic and electrostatic interactions with LPS. An MD54 analog of the same size was also designed in which a leucine residue at a heptadic position was replaced with an alanine residue. MD54 but not its analog, MMD54 induced aggregation of LPS and aided in its internalization within THP-1 monocytes. Furthermore, MD54 inhibited LPS-induced nuclear translocation of NF-κB in PMA-treated THP-1 and TLR4/MD2/CD14-transfected HEK-293T cells and the production of pro-inflammatory cytokines. In addition, in in vivo experiments, MD54 showed marked protection and survival of mice against LPS-induced inflammation and death. Overall, we have identified a short peptide with heptad repeat sequence from MD2 that can cause aggregation of LPS and abet in its internalization within THP-1 cells, resulting in attenuation of LPS-induced pro-inflammatory responses in vitro and in vivo.

Marine fish antimicrobial peptide, chrysophsin-1 possesses versatile biological activities but its non-selective nature restricts its therapeutic possibilities. Often small alterations in structural motifs result in significant changes in the properties of concerned proteins/peptides. We have identified GXXXXG motif in chrysophsin-1. Glycine residue(s) of this motif in Chrysophsin-1 was/were replaced with alanine, valine and proline residue(s). Of these, proline-substituted Chrysophsin-1 analogs exhibited significantly reduced cytotoxicity towards mammalian cells. Further, these analogs showed broad-spectrum activity against Gram-positive, Gram-negative bacteria, Methicillin-resistant Staphylococcus aureus strains and fungi and also retained antibacterial activity in presence of physiological salts, serum and at elevated temperatures indicative of their therapeutic potential. These Chrysophsin-1 analogs also inhibited lipopolysaccharide (LPS) induced pro-inflammatory responses in THP-1 cells and in murine primary macrophages. One of these single proline-substituted Chrysophsin-1 analogs inhibited LPS-stimulated pro-inflammatory cytokine production in BALB/c mice and elicited appreciable survival of mice administered with a lethal dose of LPS in a model of severe sepsis. The data for the first time showed the implication of GXXXXG motifs in functional and biological properties of an antimicrobial peptide and could be useful to design novel anti-microbial and anti-endotoxin peptides by employing this motif.

In the collectivist culture of India, family occupies a central place in organizing social and personal lives of the people. However, the forces of industrialization and urbanization are changing the life style and leading to reprioritization of values. Against this backdrop this study examined the pattern of actual and desired family values in the context of ecology, family type and generation. The sample ( n = 90) was drawn from urban, semi-urban and rural areas in central India representing parent–child pairs belonging to joint and nuclear families. Using an indigenously developed measure of family values the study revealed that ecological setting and generation significantly influenced the family value of positive interaction. The type of family emerged as a significant factor for three major values, that is, social order, manners and helping. The interaction of ecology, family type and generation were significant for the values of social order and helping. In general, the type of family and ecological setting yielded major influence in shaping values. The implications of the findings for parenting are discussed.

Introduction: Piperine (PIP) is well known multifunctional antioxidant and anti-inflammatory phytochemical that showed neuroprotection. Pre-treatment of UV-R irradiated piperine (UVR-PIP) 10 mg/kg body weight bw, intravenously showed attenuated neuroprotective effects compared to that of PIP (10µM) in PC12, cortical neuronal culture in-vitro and a rat model of focal cerebral ischemia in-vivo. Method: Neurological parameters were evaluated for UVR-PIP and PIP treated against transient focal cerebral ischemia of SD rats through quantification of infarct volume by TTC staining. In-vitro results deal with reduction of cell viability on UVR-PIP treatment in PC12 and cortical neuronal cell. The result of photodegradation of PIP under UV-R irradiation revealed the formation of photoproducts. Estimation of Mitochondrial ROS, antioxidant enzyme and non-enzyme activities in UVR-PIP and PIP treated brain tissue. Results: Results indicated OGD induced primary cortical neuron cultures and PC12 cells showed that SUN-PIP treatment decrease cell viability and increased LDH secretion compared to that of the PIP pre-treatment. In addition, Bcl-2 expression was decreases after the SUN-PIP treatment. Thus, our results demonstrated that SUN-PIP preconditioning failed to increase levels of Bcl-2 and normalized the endogeneous antioxidant, mediating the neuroprotective effects of PIP. UV-R irradiation attenuated the neuroprotective effects of PIP through modulation of the antioxidant and Bcl-2 mediated pathway. Conclusion: Thus, the ability of UV-R to serve as a modulator of this neuroprotective signaling pathway. Piperine loses some of its neuroprotective ability when irradiated by UV radiation and care has to be taken during storage to avoid exposing piperine to the sun.