Lipid-dependent conformational landscape of the ErbB2 growth factor receptor dimers

Altered lipid metabolism has been linked to cancer development and progression. Several roles have been attributed to the increased saturation and length of lipid acyl tails observed in tumors, but its effect on signaling receptors is still emerging. In this work, we have analyzed the lipid dependence of the ErbB2 growth factor receptor dimerization that plays an important role in the pathogenesis of breast cancer. We have performed coarse-grain ensemble molecular dynamics simulations to comprehensively sample the ErbB2 monomer-dimer association. Our results indicate a dynamic dimer state with a complex conformational landscape that is modulated with increasing lipid tail length. We resolve the native N-terminal "active" and C-terminal "inactive" conformations in all membrane compositions. However, the relative population of the N-terminal and C-terminal conformers is dependent on length of the saturated lipid tails. In short-tail membranes, additional non-specific dimers are observed which are reduced or absent in long-tailed bilayers. Our results indicate that the relative population as well as the structure of the dimer state is modulated by membrane composition. We have correlated these differences to local perturbations of the membrane around the receptor. Our work is an important step in characterizing ErbB dimers in healthy and diseased states and emphasize the importance of sampling lipid dynamics in understanding receptor association

Followership in Organisational Leadership Studies: A Systematic Literature Review

Although followership is just as important as leadership, it is often overlooked in leadership research due to the stereotypical belief that only leaders are responsible for organisational success and failures. However, without followers, leaders would not exist, and thus, studying followership is essential to improve our understanding of organisational leadership. This systematic literature review paper aims to contribute to the body of literature on leadership research by examining the conceptualisation of followership from both leader-centric and follower-centric perspectives. Employing the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) method as a framework, this paper conceptualises followership and examines various aspects of follower conceptualisation, including definitions, styles, and attributes. It further investigates follower-centric predictors of leadership effectiveness. The paper also examines the theoretical perspectives utilised in understanding followership

CRYPTOSOMES: A REVOLUTIONARY BREAKTHROUGH IN NOVEL DRUG DELIVERY

The vesicular drug delivery systems are promising approaches to overthrown the problems of drugs having lesser bioavailability and rapid elimination from the body. The four type of lipid based drug delivery systems are: solid-lipid particulate system, emulsion based system, solid lipid tablet and vesicular system. Cryptosomes, a novel emerging vesicular drug delivery system which can overcome the disadvantages associated with conventional drug delivery systems like high stability, increased bioavailability, sustained release, decreased elimination of rapidly metabolizable drugs etc. The word Cryptosome was orginated from Greek word ‘’Crypto’’ means hidden and ‘’Soma’’ means body. It is formed from the mixture of phospholipids like distearoyl phosphatidyl ethanolamine-polyethylene glycol (DSPE-PEG) with distearoylphosphatidylcholine. These entire information regarding its origin and formation is explained in Dinesh Kumar et al. Vesicular systems symbolizes the use of vesicles in the different fields as carrier system or additives. This review disclose various vesicular drug delivery system and point out the advancement of cryptosome in the world of drug delivery. This review would help researchers involved in the field of vesicular drug delivery

FORMULATION AND EVALUATION OF LORAZEPAM ENCAPSULATED COLLAGEN/PECTIN BUCCAL PATCH

Objective: To formulate and characterize Lorazepam loaded buccal patches using mucoadhesive, biodegradable, natural polymers-pectin (hydrophilic) and collagen (lipophilic) for treating epileptic seizures. Methods: Lorazepam loaded buccal patches were prepared by solvent casting method and were subjected to various Physico-chemical evaluation parameters to find the optimized buccal patch. The in vitro drug release study and ex vivo permeation study was carried out. The stability study and histopathological study of optimized Lorazepam loaded buccal patch was also carried out. Results: From in vitro drug release study, it was found that Lorazepam loaded buccal patch (B4) exhibited maximum drug release of 96.16 %±0.07 than other formulations at the end of 4 h, indicating an initial burst release followed by sustained release with release kinetics as Higuchi diffusion model. Based on the in vitro drug release, % drug content, % swelling index, folding endurance, B4 formulation was considered as optimised formulation and was further characterized. Ex vivo permeation study revealed that the cumulative amount of drug permeated from optimised Lorazepam loaded buccal patch (B4) was higher (3831.4±0.21µg/cm2) than marketed Midazolam buccal solution (1724±0.12 µg/cm2) and control drug solution (895.42±0.07 µg/cm2) with an enhancement ratio of 4.8. B4 formulation also showed a higher flux value (12.52±0.02µg/cm2/hr) compared to marketed formulation (5.732±0.01 µg/cm2) and control drug solution (2.563±0.03 µg/cm2) of P<0.05. The histopathological study using bovine buccal mucosa revealed that the B4 formulation is safe for buccal application. The stability study confirmed that B4 formulation is stable in both room and refrigeration conditions. Hence the formulated Lorazepam loaded buccal patch seems to be a promising carrier for the enhanced buccal delivery of Lorazepam in treating epileptic seizures. Conclusion: The formulated Lorazepam loaded collagen/pectin buccal patch was found to be an efficient and stable route for the buccal delivery of Lorazepam in treating acute epileptic seizures which could be further explored scientifically

PORPHYSOMES-A PARADIGM SHIFT IN TARGETED DRUG DELIVERY

A novel drug delivery system is the one that ensures optimum dose at the right time, at the right location. Porphysomes are among those drug delivery systems. Porphysomes are a means of vesicular drug delivery systems. They are liposome-like structures composed completely of porphyrin lipid. The porphysomes encapsulates the active medicament in vesicular structure. They are having an aqueous core which can be loaded with the medicament. They have the capacity to destroy the disease tissues. They absorb the heat in the near infrared region and release this heat to destroy the diseased tissues. Porphysomes are having immense applications in the field of positron-electron therapy (PET), photoacoustic imaging, photothermal therapy etc. This review article discusses regarding the Porphysome-the drug delivery system, its advantages and disadvantages, composition, method of preparation, applications and various aspects related to the porphysomal drug delivery

COMPARISON OF PID AND FUZZY-PID CONTROL FOR NUCLEAR STEAM BOILER LEVEL CONTROL

This paper presents control of water level of the steam boiler of nuclear power plant by using PID and Fuzzy-PID controller. In nuclear power plants, boilers are used to convert water into steam in which the water level control of boiler is very important as to provide sufficient cooling to the nuclear reactor and prevent damage of turbine blades. In order to compensate difficulty to control the level of boiler we propose the design of tuning of PID controller by a fuzzy logic controller in the level control of the steam generator of a nuclear power plant

Characterizations of synthesized laser scribed graphene/molybdenum disulfide (LSG/MoS2) hybrids for supercapacitor performance

A sustainable and organic energy storage system from oil palm lignin waste-derived laser-scribed graphene embedded with molybdenum disulfide (LSG/MoS2) is reported in this work. LSG/MoS2 hybrids were fabricated to overcome the zero-band gap of graphene, and molybdenum disulfide restacking issues, and to induce electrical conductivity. Various amounts of LSG (0.1,0.5,1.0 g) were added in a MoS2 precursor to produce a nanoscale LSG/MoS2 hybrid nanostructure via the hydrothermal method. The Raman D,G, and 2D bands of LSG confirmed the formation of graphene from lignin. The FESEM morphology of LSG/MoS2 hybrids showed a porous and large surface area anchored with 3D MoS2 nanoflower on LSG. TEM imaging revealed MoS2 decorated LSG with a lattice spacing of 0.62 and 0.27nm, corresponding to the (002) and (100) planes of MoS2. In terms of electrochemical performance, LSG with 0.1g of MoS2 has the lowest resistance, the highest specific capacitance of 6.7mF/cm2 at 0.05 mA/cm2, and excellent cyclic stability of 98.1% over 1000 cycles, based on Electrochemical Impedance Spectroscopy (EIS), Cyclic Voltammetry (CV) and Galvanostatic Charge Discharge (GCD) tests

Frequent capsule switching in 'ultra-virulent' meningococci - Are we ready for a serogroup B ST-11 complex outbreak?

The meningococcal ST-11 complex (cc11) causes large invasive disease outbreaks with high case fatality rates, such as serogroup C (MenC) epidemics in industrialised nations in the 1990s and the serogroup W epidemic currently expanding globally. Glycoconjugate vaccines are available for serogroups A, C, W and Y. Broad coverage protein-based vaccines have recently been licensed against serogroup B meningococci (MenB), however, these do not afford universal MenB protection. Capsular switching from MenC to MenB among cc11 organisms is concerning because a large MenB cc11 (B:cc11) outbreak has the potential to cause significant morbidity and mortality. This study aimed to assess the potential for licensed and developmental non-capsular meningococcal vaccines to protect against B:cc11. The population structure and vaccine antigen distribution was determined for a panel of >800 geo-temporally diverse, predominantly MenC cc11 and B:cc11 genomes. The two licensed vaccines potentially protect against many but not all B:cc11 meningococci. Furthermore, strain coverage by these vaccines is often due to a single vaccine antigen and both vaccines are highly susceptible to vaccine escape owing to the apparent dispensability of key proteins used as vaccine antigens. cc11 strains with MenB and MenC capsules warrant special consideration when formulating future non-capsular meningococcal vaccines

The Homeobox Protein CEH-23 Mediates Prolonged Longevity in Response to Impaired Mitochondrial Electron Transport Chain in C. elegans

Recent findings indicate that perturbations of the mitochondrial electron transport chain (METC) can cause extended longevity in evolutionarily diverse organisms. To uncover the molecular basis of how altered METC increases lifespan in C. elegans, we performed an RNAi screen and revealed that three predicted transcription factors are specifically required for the extended longevity of mitochondrial mutants. In particular, we demonstrated that the nuclear homeobox protein CEH-23 uniquely mediates the longevity but not the slow development, reduced brood size, or resistance to oxidative stress associated with mitochondrial mutations. Furthermore, we showed that ceh-23 expression levels are responsive to altered METC, and enforced overexpression of ceh-23 is sufficient to extend lifespan in wild-type background. Our data point to mitochondria-to-nucleus communications to be key for longevity determination and highlight CEH-23 as a novel longevity factor capable of responding to mitochondrial perturbations. These findings provide a new paradigm for how mitochondria impact aging and age-dependent diseases