Solid Lipid Nanoparticles (SLNs) with Potential as Cosmetic Hair Formulations Made from Otoba Wax and Ultrahigh Pressure Homogenization

The development and physicochemical characterization of solid lipid nanoparticles (SLNs) with potential for formulating hair cosmetic products were carried out. SLNs were made from Otoba wax, which is native to the tropical Andean region and has a high chemical composition of fatty acids with intermediate chains. SLNs were formulated by preparing wax-in-water dispersions at two internal phase proportions (low = 5% w/w and high = 20% w/w), using the same ratio of surfactant system and preservatives. The coarse dispersions were subjected to ultrahigh pressure homogenization (UHPH), and thermal stability assays for 4 weeks were carried out, where changes in Creaming Index, droplet size, polydispersity, viscosity, zeta potential, conductivity, and pH were evaluated. The results showed that Otoba wax has a required HLB value around 9 and is mainly composed of lauric (~35%) and myristic (~45%), which have been reported to improve the condition of hair loss. Regarding the development on SLNs, it was found that the internal phase concentration did not considerably affect the physicochemical and microbiological properties. Likewise, it was found that UHPH enabled the production of SLNs with particle sizes <200 nm, low polydispersity (<0.3), high zeta potential values, and suitable physical and microbiological stability. Therefore, Otoba wax has potential for the development of SLNs applicable to cosmetic formulations, especially for hair products.

Distinct roles for dynein light intermediate chains in neurogenesis, migration, and terminal somal translocation

Cytoplasmic dynein participates in multiple aspects of neocortical development. These include neural progenitor proliferation, morphogenesis, and neuronal migration. The cytoplasmic dynein light intermediate chains (LICs) 1 and 2 are cargo-binding subunits, though their relative roles are not well understood. Here, we used in utero electroporation of shRNAs or LIC functional domains to determine the relative contributions of the two LICs in the developing rat brain. We find that LIC1, through BicD2, is required for apical nuclear migration in neural progenitors. In newborn neurons, we observe specific roles for LIC1 in the multipolar to bipolar transition and glial-guided neuronal migration. In contrast, LIC2 contributes to a novel dynein role in the little-studied mode of migration, terminal somal translocation. Together, our results provide novel insight into the LICs’ unique functions during brain development and dynein regulation overall.

Dynein-2 intermediate chains play crucial but distinct roles in primary cilia formation and function

The dynein-2 microtubule motor is the retrograde motor for intraflagellar transport. Mutations in dynein-2 components cause skeletal ciliopathies, notably Jeune syndrome. Dynein-2 contains a heterodimer of two non-identical intermediate chains, WDR34 and WDR60. Here, we use knockout cell lines to demonstrate that each intermediate chain has a distinct role in cilium function. Using quantitative proteomics, we show that WDR34 KO cells can assemble a dynein-2 motor complex that binds IFT proteins yet fails to extend an axoneme, indicating complex function is stalled. In contrast, WDR60 KO cells do extend axonemes but show reduced assembly of dynein-2 and binding to IFT proteins. Both proteins are required to maintain a functional transition zone and for efficient bidirectional intraflagellar transport. Our results indicate that the subunit asymmetry within the dynein-2 complex is matched with a functional asymmetry between the dynein-2 intermediate chains. Furthermore, this work reveals that loss of function of dynein-2 leads to defects in transition zone architecture, as well as intraflagellar transport.

Synthesis and Applications of Bisheterocyclic Compounds

Background: The synthesis of a variety of bisheterocyclic compounds has received a great attention not only as main chain polymers but also because many biologically active natural and synthetic products have molecular symmetry. In the synthesis of bisheterocyclic, researchers tried to extend the existing method by using a broad range of protocols to improve the various scope and limitations regarding their yield, purity and mostly on the various biological applications. <p> Objective: The significance of this review lies in the fact that bisheterocycles reported here display diverse chemical, structural and biological properties which makes them potential candidates for the further investigations. Conclusion: This review article is associated with the study of the synthesis and varied applications of different bisheterocycles. These compounds have been built around the variety of intermediate chains such aliphatic, olefinic, alkynic and aromatic linkers. The presence of two heterocyclic moieties together in the same molecule either symmetrically or non-symmetrically has been found to influence the biological profiles of the resultant bis organic molecules. So, there is plenty of scope upon the development of the new bisheterocyclic in order to investigate the effect of the length and flexibility of the linkers upon their biological and other properties.

LIM kinase1 regulates mitotic centrosome integrity via its activity on dynein light intermediate chains

Abnormal centrosome number and function have been implicated in tumour development. LIM kinase1 (LIMK1), a regulator of actin cytoskeleton dynamics, is found to localize at the mitotic centrosome. However, its role at the centrosome is not fully explored. Here, we report that LIMK1 depletion resulted in multi-polar spindles and defocusing of centrosomes, implicating its involvement in the regulation of mitotic centrosome integrity. LIMK1 could influence centrosome integrity by modulating centrosomal protein localization at the spindle pole. Interestingly, dynein light intermediate chains (LICs) are able to rescue the defects observed in LIMK1-depleted cells. We found that LICs are potential novel interacting partners and substrates of LIMK1 and that LIMK1 phosphorylation regulates cytoplasmic dynein function in centrosomal protein transport, which in turn impacts mitotic spindle pole integrity.

Dynein-2 intermediate chains play crucial but distinct roles in primary cilia formation and function

The dynein-2 microtubule motor is the retrograde motor for intraflagellar transport. Mutations in dynein-2 components cause skeletal ciliopathies, notably Jeune syndrome. Dynein-2 comprises a heterodimer of two non-identical intermediate chains, WDR34 and WDR60. Here, we use knockout cell lines to demonstrate that each intermediate chain has a distinct role in cilia function. Both proteins are required to maintain a functional transition zone and for efficient bidirectional intraflagellar transport, only WDR34 is essential for axoneme extension. In contrast, only WDR60 is essential for co-assembly of the other subunits. Furthermore, WDR60 cannot compensate for loss of WDR34 or vice versa. This work defines a functional asymmetry to match the subunit asymmetry within the dynein-2 motor. Analysis of causative point mutations in WDR34 and WDR60 can partially restore function to knockout cells. Our data show that Jeune syndrome is caused by defects in transition zone architecture as well as intraflagellar transport.SUMMARYHere, Vuolo and colleagues use engineered knockout human cell lines to define roles for dynein-2 intermediate chains. WDR34 is required for axoneme extension, while WDR60 is not. Both subunits are required for cilia transition zone organization and bidirectional intraflagellar transport.