In silico characterization and identification of compound heterozygous variants in H/ACA Ribonucleoprotein Assembly Factor (SHQ1) from Indian population.

Background: H/ACA small nucleolar ribonucleoproteins (snoRNP) form a complex with multiple proteins to accomplish the pseudouridylation of rRNA. The assembly of H/ACA small nucleolar ribonucleoproteins (snoRNP) is initiated by H/ACA ribonucleoprotein Assembly factor, that is, SHQ1. Mutations in SHQ1 have been reported to cause two disorders namely, dystonia-35 childhood onset (OMIM*619921) and neurodevelopmental disorder with seizures and dystonia (OMIM*619922), both of which are inherited in an autosomal recessive manner. Considering the high genetic and clinical diversity of SHQ1-related clinical features and the importance of SHQ1 in the assembly of the H/ACA snoRNP complex, it is important to take a systematic approach to delineate the genetic diagnosis and impact of mutations on protein structure and stability. Methods: Whole exome sequencing followed by Sanger validation was performed in an individual with the clinical features of neurodevelopmental disorder with seizures and dystonia (OMIM*619922). Protein modeling studies of all the reported SHQ1 variants to date were performed using freely available web servers Interactive Tree of Life, String, BioGrid, ShinyGO, DAVID, and Pathvix. Protein structures were visualized using Pymol. Results and Discussion: We identified compound heterozygous variants, one known frameshift deletion c. 828_831del, p.(Asp277Serfs*27) and the other novel missense variant c. 1157A>C, p.(Tyr386Ser) found in an individual with neurodevelopmental disorder, seizures, movement disorder, and hypomyelination leukodystrophy on neuroimaging. Protein-interactome studies identified potential genetic interactors that include GAR1, NAF1, TRUB1, UTP15, DKC1, NOP10, NPHOSPH 10, KRR1, NOP58, NOP56, FBL, RRP9, NHP2, RUVBL1, and RUVBL2. Ribosome biogenesis in eukaryotes, RNA polymerase, RNA transport, spliceosome, ribosome, cytosolic DNA-sensing pathway, DNA replication, mismatch repair, base excision repair, nucleotide excision repair, and basal transcription factors process were identified as the linked pathways with the prioritized genes. Conclusion: In conclusion, a sophisticated genotype and phenotype correlation followed by linking the genes to the key biological pathways opens new avenues to understand disease pathology and plan for therapeutic interventions.

Emergent human-like covert attention in feedforward convolutional neural networks.

Covert attention allows the selection of locations or features of the visual scene without moving the eyes. Cues and contexts predictive of a target's location orient covert attention and improve perceptual performance. The performance benefits are widely attributed to theories of covert attention as a limited resource, zoom, spotlight, or weighting of visual information. However, such concepts are difficult to map to neuronal populations. We show that a feedforward convolutional neural network (CNN) trained on images to optimize target detection accuracy and with no explicit incorporation of an attention mechanism, a limited resource, or feedback connections learns to utilize cues and contexts in the three most prominent covert attention tasks (Posner cueing, set size effects in search, and contextual cueing) and predicts the cue/context influences on human accuracy. The CNN's cueing/context effects generalize across network training schemes, to peripheral and central pre-cues, discrimination tasks, and reaction time measures, and critically do not vary with reductions in network resources (size). The CNN shows comparable cueing/context effects to a model that optimally uses image information to make decisions (Bayesian ideal observer) but generalizes these effects to cue instances unseen during training. Together, the findings suggest that human-like behavioral signatures of covert attention in the three landmark paradigms might be an emergent property of task accuracy optimization in neuronal populations without positing limited attentional resources. The findings might explain recent behavioral results showing cueing and context effects across a variety of simple organisms with no neocortex, from archerfish to fruit flies.

Maxillary reservoir denture to overcome radiation-induced xerostomia - Light at the end of the tunnel.

Xerostomia is a subjective symptom of dry mouth. It can occur as a part of the systemic disease, drug-induced side effect, or following therapeutic radiation therapy to the head-and-neck region. The primary complication faced by these xerostomic patients is the difficulty in retention of removable dentures. It is important to recognize that the prosthodontic management of these patients requires special attention and care. In an attempt to overcome the presence of xerostomia, several techniques of introducing reservoirs into the dentures containing salivary substitutes have been proposed. This case report presents a simplified approach for the construction of a reservoir in the maxillary denture, specifically in patients where other treatment modalities have failed. This technique provided excellent lubrication to oral tissues, hygienic for the patient, and utilized routine denture base material.

Modified Tray with Mesh Design for the Management of Flabby Ridge: A Case Report.

Flabby ridge is an excessive movable fibrous tissue, usually affecting the maxillary and mandibular edentulous ridges. It is a typical finding frequently observed in the maxillary anterior region. It usually occurs when natural teeth oppose an edentulous ridge or in long-term denture wearers. The management of flabby ridges includes surgical intervention, implant-retained prostheses, and conventional dentures fabricated using the modified impression technique. This case report depicts a modified technique with the utilization of an aluminum mesh double tray and polyvinylsiloxane impression material for the management of a flabby ridge in the maxillary arch.

Rehabilitation of ocular defect: A modified technique to produce corneal prominence.

Esthetics is a vital social concern. The loss of any part of the body can be an extremely discouraging occasion in a person's life. Loss of an eye because of tumors, congenital abnormalities, and trauma is one such troublesome situation. Eye prosthesis boosts the morale and makes the life socially acceptable. A correctly placed ocular prosthesis should reestablish the normal opening of the eye, support the eyelids, reestablish a degree of movement, and be satisfactorily held and esthetically satisfying. A customized acrylic eye fulfills all these requirements. In the current article, a new and economic technique was used to duplicate corneal prominence using a clear acrylic shell. The characterization was further done to give a life-like appearance to the eye prostheses.

Terminal supraparticle assemblies from similarly charged protein molecules and nanoparticles.

Self-assembly of proteins and inorganic nanoparticles into terminal assemblies makes possible a large family of uniformly sized hybrid colloids. These particles can be compared in terms of utility, versatility and multifunctionality to other known types of terminal assemblies. They are simple to make and offer theoretical tools for designing their structure and function. To demonstrate such assemblies, we combine cadmium telluride nanoparticles with cytochrome C protein and observe spontaneous formation of spherical supraparticles with a narrow size distribution. Such self-limiting behaviour originates from the competition between electrostatic repulsion and non-covalent attractive interactions. Experimental variation of supraparticle diameters for several assembly conditions matches predictions obtained in simulations. Similar to micelles, supraparticles can incorporate other biological components as exemplified by incorporation of nitrate reductase. Tight packing of nanoscale components enables effective charge and exciton transport in supraparticles and bionic combination of properties as demonstrated by enzymatic nitrate reduction initiated by light absorption in the nanoparticle.

Spontaneous self-organization enables dielectrophoresis of small nanoparticles and formation of photoconductive microbridges.

Detailed understanding of the mechanism of dielectrophoresis (DEP) and the drastic improvement of its efficiency for small size-quantized nanoparticles (NPs) open the door for the convergence of microscale and nanoscale technologies. It is hindered, however, by the severe reduction of DEP force in particles with volumes below a few hundred cubic nanometers. We report here DEP assembly of size-quantized CdTe nanoparticles (NPs) with a diameter of 4.2 nm under AC voltage of 4-10 V. Calculations of the nominal DEP force for these NPs indicate that it is several orders of magnitude smaller than the force of the Brownian motion destroying the assemblies even for the maximum applied AC voltage. Despite this, very efficient formation of NP bridges between electrodes separated by a gap of 2 µm was observed even for AC voltages of 6 V and highly diluted NP dispersions. The resolution of this conundrum was found in the intrinsic ability of CdTe NPs to self-assemble. The species being assembled by DEP are substantially bigger than the individual NPs. DEP assembly should be treated as a process taking place for NP chains with a length of ~140 nm. The self-assembled chains increase the nominal volume where the polarization of the particles takes place, while retaining the size-quantized nature of the material. The produced NP bridges were found to be photoactive, producing photocurrent upon illumination. DEP bridges of quantum confined NPs can be used in fast parallel manufacturing of novel MEMS components, sensors, and optical and optoelectronic devices. Purposeful engineering of self-assembling properties of NPs makes possible further facilitation of the DEP and increase of complexity of the produced nano- and microscale structures.

Light-controlled self-assembly of semiconductor nanoparticles into twisted ribbons.

The collective properties of nanoparticles manifest in their ability to self-organize into complex microscale structures. Slow oxidation of tellurium ions in cadmium telluride (CdTe) nanoparticles results in the assembly of 1- to 4-micrometer-long flat ribbons made of several layers of individual cadmium sulfide (CdS)/CdTe nanocrystals. Twisting of the ribbons with an equal distribution of left and right helices was induced by illumination with visible light. The pitch lengths (250 to 1500 nanometers) varied with illumination dose, and the twisting was associated with the relief of mechanical shear stress in assembled ribbons caused by photooxidation of CdS. Unusual shapes of multiparticle assemblies, such as ellipsoidal clouds, dog-bone agglomerates, and ribbon bunches, were observed as intermediate stages. Computer simulations revealed that the balance between attraction and electrostatic repulsion determines the resulting geometry and dimensionality of the nanoparticle assemblies.

Beyond molecular recognition: using a repulsive field to tune interfacial valency and binding specificity between adhesive surfaces.

Surface-bound biomolecular fragments enable "smart" materials to recognize cells and other particles in applications ranging from tissue engineering and medical diagnostics to colloidal and nanoparticle assembly. Such smart surfaces are, however, limited in their design to biomolecular selectivity. This feature article demonstrates, using a completely nonbiological model system, how specificity can be achieved for particle (and cell) binding, employing surface designs where immobilized nanoscale adhesion elements are entirely nonselective. Fundamental principles are illustrated by a model experimental system where 11 nm cationic nanoparticles on a planar negative silica surface interact with flowing negative silica microspheres having 1.0 and 0.5 microm diameters. In these systems, the interfacial valency, defined as the number of cross-bonds needed to capture flowing particles, is tunable through ionic strength, which alters the range of the background repulsion and therefore the effective binding strength of the adhesive elements themselves. At high ionic strengths where long-range electrostatic repulsions are screened, single surface-bound nanoparticles capture microspheres, defining the univalent regime. At low ionic strengths, competing repulsions weaken the effective nanoparticle adhesion so that multiple nanoparticles are needed for microparticle capture. This article discusses important features of the univalent regime and then illustrates how multivalency produces interfacial-scale selectivity. The arguments are then generalized, providing a possible explanation for highly specific cell binding in nature, despite the degeneracy of adhesion molecules and cell types. The mechanism for the valency-related selectivity is further developed in the context of selective flocculation in the colloidal literature. Finally, results for multivalent binding are contrasted with the current thinking for interfacial design and the presentation of adhesion moieties on engineered surfaces.

Composite Layer-by-Layer (LBL) assembly with inorganic nanoparticles and nanowires.

New assembly techniques are required for creating advanced materials with enough structural flexibility to be tuned for specific applications, and to be practical, the techniques must be implemented at relatively low cost. Layer-by-layer (LBL) assembly is a simple, versatile, and significantly inexpensive approach by which nanocomponents of different groups can be combined to coat both macroscopically flat and non-planar (e.g., colloidal core-shell particles) surfaces. Compared with other available assembly methods, LBL assembly is simpler and more universal and allows more precise thickness control at the nanoscale. LBL can be used to combine a wide variety of species--including nanoparticles (NPs), nanosheets, and nanowires (NWs)--with polymers, thus merging the properties of each type of material. This versatility has led to recent exceptional growth in the use of LBL-generated nanocomposites. This Account will focus on the materials and biological applications of introducing inorganic nanocrystals into polymer thin films. Combining inorganic NPs and NWs with organic polymers allows researchers to manipulate the unique properties in the nanomaterial. We describe the LBL assembly technique for introducing metallic NPs into polymers in order to generate a material with combined optomechanical properties. Similarly, LBL assembly of highly luminescent semiconductor NPs like HgTe or CdTe with poly(diallyldimethylammonium chloride) (PDDA) was used to create uniform optical-quality coatings made on optical fibers and tube interiors. In addition, LBL assembly with inorganic nanosheets or clay molecules is reported for fabricating films with strong mechanical and ion transport properties, and the technique can also be employed to prepare Au/TiO(2) core/sheath NWs. The LBL approach not only will be useful for assembly of inorganic nanocrystals with various polymers but can be further applied to introduce specific functions. We discuss how the expanded use of NWs and carbon nanotubes (CNTs) in nanocomposite materials holds promise in the design of conductive films and new nanoscale devices (e.g., thin-film transistors). New photonic materials, sensors, and amplifiers can be constructed using multilayer films of NPs and can enable fabrication of hybrid devices. On the biological side, inorganic nanoshells were used as assembly tools with the goal of detecting neurotransmitters (specifically, dopamine) directly inside brain cells. In addition, the stability of different cell lines was tested for fabricating biocompatible films using LBL. NP LBL assembly was also used for homogeneous and competitive fluorescence quenching immunoassay studies for biotin and anti-biotin immunoglobulin molecules. Finally, introduction of biomolecules with inorganic NPs for creating biocompatible surfaces could also lead to new directions in the field of biomedical applications.

Manipulating microparticles with single surface-immobilized nanoparticles.

This experimental study explores the capture and manipulation of micrometer-scale particles by single surface-immobilized nanoparticles. The nanoparticles, approximately 10 nm in diameter, are cationic and therefore attract the micrometer-scale silica particles in an analyte suspension. The supporting surface on which the nanoparticles reside is negative (also silica) and repulsive toward approaching microparticles. In the limit where there are as few as 9 nanoparticles per square micrometer of collector, it becomes possible to capture and hold micrometer-scale silica particles with single nanoparticles. The strong nanoparticle-microparticle attractions, their nanometer-scale protrusion forward of the supporting surface, and their controlled density on the supporting surface facilitate microparticle-surface contact occurring through a single nanoelement. This behavior differs from most particle-particle, cell-cell, or particle (or cell)-surface interactions that involve multiple ligand-receptor bonds or much larger contact areas. Despite the limited contact of microparticles with surface-immobilized nanoparticles, microparticles resist shear forces of 9 pN or more but can be released through an increase in the ionic strength. The ability of nanoparticles to reversibly trap and hold much larger targets has implications in materials self-assembly, cell capture, and sorting applications, whereas the single point of contact affords precision in particle manipulation.

Reversible loading and unloading of nanoparticles in "exponentially" growing polyelectrolyte LBL films.

The exponentially growing layer-by-layer (LBL) films made from poly(diallyldimethylammonium chloride) (PDDA) and poly(acrylic acid) (PAA) were used to load and unload the CdTe nanoparticles (NPs). The reversible loading of NPs were investigated through UV-vis studies and further confirmed by confocal microscopy. In addition the LBL films were also compared for the release kinetics for pH 9 and 7 and films capped with (PDDA-PSS)10 layers. The amount of released particles at pH 9 was found to be at least 2 orders of magnitude higher than those at pH 7 and with (PDDA-PSS)10 capped layers after 25 h. This variation in film response for CdTe-particle release presents a route for studies in which highly swollen exponentially growing LBL films can be loaded with functionalized NPs for biological applications and explored as carriers to hold the NPs inside the films for self-assembly.

Controlled nanoparticleassembly through protein conformational changes.

Selective surface recognition by proteins provides programmed bottom-up assembly of synthetic nanomaterials. We have investigated the controlled self-assembly of functionalized gold nanoparticles (Au-TAsp) with cytochrome c (Cyt c) and apoCyt c through complementary electrostatic interactions. Au-TAsp formed discrete, water-soluble adducts with native Cyt c, whereas unfolded apoCyt c induced nanocomposite formation at high Cyt c : Au-TAsp ratios. The binding of random-coil apoCyt c to Au-TAsp at low ratios induced α-helix formation in soluble nanocomposites, but at elevated ratios insoluble micron-scale aggregates were formed. The local structure of the assemblies was critically dependent on the Cyt c : Au-TAsp ratio. The dispersibility of apoCyt c-Au-TAsp was pH dependent, providing rapid and reversible control over nanocomposite assembly. The apoCyt c-Au-TAsp aggregates could likewise be disassembled through proteolytic cleavage of apoCyt c, demonstrating the ability to selectively remodel these hybrid materials.

Integrated magnetic bionanocomposites through nanoparticle-mediated assembly of ferritin.

Magnetic (FePt) and nonmagnetic (Au) nanoparticles were used to assemble ferritin into near-monodisperse bionanocomposites featuring regular interparticle spacing. The FePt/ferritin assemblies are integrated magnetic materials with ferritin providing added magnetic volume fraction to the magnetic nanocomposite. These assemblies differ from either of their constituent particles in terms of blocking temperature (TB), net magnetic moment, coercivity, and remnance.

Biomimetic interactions of proteins with functionalized nanoparticles: a thermodynamic study.

Gold nanoparticles (NPs) functionalized with L-amino acid-terminated monolayers provide an effective platform for the recognition of protein surfaces. Isothermal titration calorimetry (ITC) was used to quantify the binding thermodynamics of these functional NPs with alpha-chymotrypsin (ChT), histone, and cytochrome c (CytC). The enthalpy and entropy changes for the complex formation depend upon the nanoparticle structure and the surface characteristics of the proteins, e.g., distributions of charged and hydrophobic residues on the surface. Enthalpy-entropy compensation studies on these NP-protein systems indicate an excellent linear correlation between DeltaH and TDeltaS with a slope (alpha) of 1.07 and an intercept (TDeltaS0) of 35.2 kJ mol(-1). This behavior is closer to those of native protein-protein systems (alpha = 0.92 and TDeltaS0 = 41.1 kJ mol(-1)) than other protein-ligand and synthetic host-guest systems.

Chiral translation and cooperative self-assembly of discrete helical structures using molecular recognition dyads.

Complementary diaminopyridine (DAP) and flavin derivatives self-assemble into discrete helically stacked tetrads in hydrocarbon solvents. The self-assembled structure was demonstrated through induced circular dichroism using DAPs with chiral side-chains and flavin with achiral side-chains. Flavin derivatives with chiral side-chains were synthesized; cooperativity in the self-assembly was established through circular dichroism (CD) profiles and melting curves. It was found that placing stereocenters in both recognition units resulted in a strong bisignated profile and enhancement of complex stability, indicative of cooperative self-assembly.