Kinds Of Molecules Research Articles

Nanobody: outstanding features for diagnostic and therapeutic applications.

Nanobodies (Nbs) have arisen as an alternative to conventional antibodies (Abs) and show great potential when used as tools in different biotechnology fields such as diagnostics and therapy. Different approaches have been described for the production of Nbs and these methods face new challenges focused on improving yield, affinity, and reducing production costs. This review summarizes these challenges, and also the latest advances in the detection of different kinds of molecules, such as proteins and small molecules, and describes their potential use for noninvasive in vivo imaging and for in vitro assays. Moreover, the unique properties of Nbs are outlined like internalization, size, thermal and chemical stability, affinity, blood clearance, and labeling procedures. Concerning therapeutic applications, we highlight some already reported examples about Nbs being used for the treatment of several diseases such as cancer, neurodegenerative or infectious diseases among others. Finally, future trends, opportunities, and disadvantages are also discussed.

Unraveling Factors Leading to High Pseudocapacitance of Redox-Active Small Aromatics on Graphene

Graphene sheets functionalized by redox-active small aromatics can exhibit enhanced capacitance because of the introduced faradaic process. However, the immense number of possible molecules for energy storage makes the selection of the appropriate ones difficult. This study combines experiment and theory to unveil factors behind the different pseudocapacitance contributions of some aromatic isomers adsorbed onto graphene, aiming to provide a guideline for computationally screening out optimal molecules for supercapacitor electrodes. Eight kinds of molecules containing amino groups are intentionally selected to functionalize N-doped graphene (NG) and their electrochemical properties are compared. The highest occupied molecular orbital level of a molecule is found to play an important role in rendering a high pseudocapacitance. Also, remarkable efficacies from two kinds of molecules, 4-aminophenol and 1,5-naphthalenediamine (1,5-NAPD), are unveiled, and the role of the amino group in charge storage is discu...

Application of molecular framework-based data-mining method in the search for beta-secretase 1 inhibitors through drug repurposing

Targeting beta-secretase 1, also known as beta-amyloid precursor protein-cleaving enzyme (BACE-1) for the inhibition of amyloid production, has been intensely studied in the last decades in the search for stopping Alzheimer’s disease (AD) progression. The chances of finding a druggable BACE-1 inhibitor may be increased by drug repurposing, as this kind of molecules already fulfil certain requirements needed for further advancement. The study describes the development and application of a data-mining method based on molecular frameworks and descriptor values of tested BACE-1 inhibitors, suitable for filtering large compound databases, in order to find molecules with high potency against this protease. A total of 465 compounds extracted from the literature, tested against BACE-1, were analysed for finding molecular descriptor values and frameworks that ensure a high probability of strong inhibition. Resulting conclusions were used for filtering DrugBank database, containing ∼8700 approved and experimental drugs, obtaining 26 structures characterized by four major Bemis–Murcko frameworks: 2‐[3‐(2‐cyclohexylethyl)cyclohexyl]‐decahydronaphthalene, 3‐(2‐cyclohexylethyl)‐1,1′‐bi(cyclohexane), [5‐(cyclohexylmethyl)‐8‐cyclopentyloctyl]cyclohexane and (3‐cyclohexylcyclopentyl)cyclohexane. The compounds were further studied by molecular docking using the structure of the closed form of the enzyme, which revealed seven compounds already involved in trials targeting BACE-1 inhibition, confirming the method’s specificity. The compounds that afforded the best binding energies were DB06925 (tyrosine-protein kinase inhibitor), DB12285 (Verubecestat) and DB08899 (Enzalutamide). Moreover, docking results indicated several other molecules with high in silico inhibitory potency that can be further studied for developing a potential treatment for AD.Communicated by Ramaswamy H. Sarma

Clustermatch: discovering hidden relations in highly diverse kinds of qualitative and quantitative data without standardization.

Heterogeneous and voluminous data sources are common in modern datasets, particularly in systems biology studies. For instance, in multi-holistic approaches in the fruit biology field, data sources can include a mix of measurements such as morpho-agronomic traits, different kinds of molecules (nucleic acids and metabolites) and consumer preferences. These sources not only have different types of data (quantitative and qualitative), but also large amounts of variables with possibly non-linear relationships among them. An integrative analysis is usually hard to conduct, since it requires several manual standardization steps, with a direct and critical impact on the results obtained. These are important issues in clustering applications, which highlight the need of new methods for uncovering complex relationships in such diverse repositories. We designed a new method named Clustermatch to easily and efficiently perform data-mining tasks on large and highly heterogeneous datasets. Our approach can derive a similarity measure between any quantitative or qualitative variables by looking on how they influence on the clustering of the biological materials under study. Comparisons with other methods in both simulated and real datasets show that Clustermatch is better suited for finding meaningful relationships in complex datasets. Files can be downloaded from https://sourceforge.net/projects/sourcesinc/files/clustermatch/ and https://bitbucket.org/sinc-lab/clustermatch/. In addition, a web-demo is available at http://sinc.unl.edu.ar/web-demo/clustermatch/. Supplementary data are available at Bioinformatics online.

Layer by Layer Mesoporous Silica-Hyaluronic Acid-Cyclodextrin Bifunctional "Lamination": Study of the Application of Fluorescent Probe and Host⁻Guest Interactions in the Drug Delivery Field.

The layer-by-layer technique was exploited to adjust the magnitude of the host–guest interactions between adamantane and cyclodextrin. The effect depends on numerous complex and changeable growth profiles of the films and the number of bilayers. These composite films of mesoporous silica nanoparticles and hyaluronic acid–cyclodextrin(HA-CD) were constructed to load the fluorescent dyes and peptides. The release rates of these molecules would decrease with an increase in the number of layers. A laser scanning confocal microscope was utilized to obtain the diffusion coefficient of fluorescein isothiocyanate. Hybrid films could be applied to increase the loading of different kinds of molecules and could also be integrated into the lamination to delay the rate of release.

Analyzing what single-use bags release

The biotech industry is beginning to replace metal vats in the manufacturing process with single-use plastic bags. But concerns remain about whether compounds could leach out of the films inside the bags. Such compounds could negatively affect cells during biomanufacturing or persist through purification processes and end up in protein drug formulations, causing a potential risk to patients. A team led by Jonathan Bones of the National Institute for Bioprocessing Research & Training, in Ireland, has measured the compounds released by 34 single-use bags from five suppliers (Anal. Chem. 2018, DOI: 10.1021/acs.analchem.8b01208). The team looked for two kinds of molecules: extractables, which represent all possible compounds that could be released, and leachables, which would be present only under normal conditions. To identify the extractables, the researchers extracted bag films with four solvents chosen to represent potential worst-case scenarios in biomanufacturing. They obtained the leachables by using c...

Enzyme based amperometric biosensors

Current research on enzyme based electrochemical biosensors deals essentially with the same target analytes as was at focus in the early days of biosensor research, that is those within the clinical/medical, food/agriculture, and environmental fields 1.• , 2. , 3. , 4. , 5. , 6. , 7. , 8. , 9.• , 10. , 11. , 12. , 13. . However, there has been substantial progress through the years and progress continues, as resumed in Figure 1 A. One of the major differences is that (bio)electrochemists finally seem to start to understand what kind of molecules they deal with, that is with biological molecules and vice versa, biochemists, (micro)biologists start to become interested in (bio)electrochemistry. This is clearly shown for example in the recent very intense research on biofuel cells 14. , 15. , 16. , 17.• , 18. , 19. , 20. , 21. , 22. , 23. , 24. , 25. , 26. and lately also on biosupercapacitors [27] that has absolutely had a great influence on current research on enzyme based biosensors and bioelectrochemistry as a whole.

Sabellastarte magnifica Carboxypeptidase Inhibitor: The first Kunitz inhibitor simultaneously interacting with carboxypeptidases and serine proteases

Multi-domain inhibitors capable to block the activity of different classes of proteases are not very common in nature. However, these kinds of molecules are attractive systems for biomedical or biotechnological applications, where two or more different targets need to be neutralized. SmCI, the Sabellastarte magnifica Carboxypeptidase Inhibitor, is a tri-domain BPTI-Kunitz inhibitor capable to inhibit serine proteases and A-like metallocarboxypeptidases. The BPTI-Kunitz family of proteins includes voltage gated channel blockers and inhibitors of serine proteases. SmCI is therefore, the only BPTI-Kunitz protein capable of inhibiting metallocarboxypeptidases. The X-ray structure of the SmCI-carboxypeptidase A complex previously obtained by us, revealed that this enzyme interacts with SmCI N-tail. In the complex, the reactive loops for serine protease inhibition remain fully exposed to the solvent in each domain, suggesting SmCI can simultaneously interact with multiple serine proteases. The twofold goals of this study were: i) to establish serine proteases-SmCI binding stoichiometry, given that the inhibitor is comprised of three potential binding domains; and ii) to determine whether or not SmCI can simultaneously bind both classes of enzymes, to which it binds individually. Our experimental approach included a variety of techniques for the study of protein-protein interactions, using as model enzymes pancreatic trypsin, elastase and carboxypeptidase A. In particular, we combined information obtained from gel filtration chromatography, denaturing electrophoresis, nuclear magnetic resonance spectroscopy and enzyme inhibition assays. Our results show that SmCI is able to bind three trypsin molecules under saturating conditions, but only one elastase interacts with the inhibitor. Additionally, we demonstrated that SmCI can bind serine proteases and carboxypeptidases at the same time (at least in the ratio 1:1:1), becoming the first protease inhibitor that simultaneously blocks these two mechanistic classes of enzymes.

(Invited) Functionalization of Carbon Nanotubes in a Micellar Environment

A key issue for applications of colloidal nanoobjects is related to their solubility in water. Indeed, their aggregation results in the deterioration of their intrinsic properties. In order to solve this problem, many strategies have been developed. As far as carbon nanotubes are concerned, the best way to solubilize them in water while preserving their outstanding properties is to use a micellar environment. As a consequence the chemistry of carbon nanotubes in micelles is a growing field of research. For instance, people have grafted photoswitches on the wall of nanotubes, have doped nanotubes with diazonium and even performed polymerization in micelles [1-4]. In this presentation, we will present our recent results on the functionalization of carbon nanotubes with different kind of molecules in a micellar environment (porphyrins [5, 6], polymers [7]…). In particular, we will focus on the influence of the molecules on the optical properties of carbon nanotubes both on ensemble and at the single object level.

Extra low friction coefficient caused by the formation of a solid-like layer: A new lubrication mechanism found through molecular simulation of the lubrication of MoS2 nanoslits

Abstract Monolayer molybdenum disulfide (MoS2) is a novel two-dimensional material that exhibits potential application in lubrication technology. In this work, molecular dynamics was used to investigate the lubrication behaviour of different polar fluid molecules (i.e., water, methanol and decane) confined in monolayer MoS2 nanoslits. The pore width effect (i.e., 1.2, 1.6 and 2.0 nm) was also evaluated. Results revealed that decane molecules exhibited good lubricating performance compared to the other two kinds of molecules. The friction coefficient followed the order of decane

PIBF+ extracellular vesicles from mouse embryos affect IL-10 production by CD8+ cells

Earlier evidence suggests, that the embryo signals to the maternal immune system. Extracellular vesicles (EVs) are produced by all types of cells, and because they transport different kinds of molecules from one cell to the other, they can be considered as means of intercellular communication. The aim of this work was to test, whether the embryo is able to produce sufficient amounts of EVs to alter the function of peripheral lymphocytes. Embryo-derived EVs were identified by their Annexin V biding capacity, and sensitivity to Triton X dependent lysis, using flow cytometry. Transmission electron microscopy was used to detect EVs at the implantation site. Progesterone-induced blocking factor (PIBF) expression in embryo-derived EVs was demonstrated with immuno-electron microscopy. The % of IL-10 + murine lymphocytes was determined by flow cytometry. EVs were present in embryo culture media, but not in empty media. Mouse embryo-derived EVs adhere to the surface of both CD4+ and CD8+ murine peripheral T lymphocytes, partly, via phosphatidylserine binding. The number of IL-10+ murine peripheral CD8+ cells increases in the presence of embryo-derived EVS, and this effect is counteracted by pre-treatment of EVs with an anti-PIBF antibody, suggesting that the embryo communicates with the maternal immune system via EVs.

Functionalization of the Si(1 1 1) 7 × 7 substrate with coronene molecules using simple molecular source

Abstract The present paper aims at describing a source designed and constructed to generate an organic molecular beam under ultrahigh vacuum conditions. The presented construction solution of the evaporation source allows for independent deposition of three different kinds of molecules. The probability of molecules fragmentation is minimized by using a thermocouple being in contact with a molecular crucible, which enables precise temperature control. In addition, cleanness and molecular beam density are monitored using a quadrupole mass spectrometer and quartz microbalance, respectively. The operational parameters of the molecular source are optimized and deposition rates are measured for the coronene molecule in the sublimation temperature range between 430 K and 460 K. The analysis of scanning tunneling microscope images of the Si(1 1 1) 7 × 7 substrate covered with the sub-monolayer of coronene molecules and comparison with previously published data has been used for verification of the molecular source operation.

Design and synthesis of organic sensitizers with enhanced anchoring stability in dye-sensitized solar cells

Abstract D-π-A dyes have received a special attention in the field of dye-sensitized solar cells (DSSCs). In this kind of molecules, the acceptor group (A) generally acts as an anchor, enabling the adsorption of the dye onto the metal oxide substrate (TiO2) and providing a good electron injection. The search for new anchors represents a critical factor for the development of improved DSSCs and in recent years has been a very active research field. This mini-review focuses especially on our work on pyridine-derived anchoring groups for D-π-A dyes, with a special regard on the preparation and characterization of three different families of dyes and a critical evaluation of their stability and efficiency.

LncRNA Structural Characteristics in Epigenetic Regulation.

The rapid development of new generation sequencing technology has deepened the understanding of genomes and functional products. RNA-sequencing studies in mammals show that approximately 85% of the DNA sequences have RNA products, for which the length greater than 200 nucleotides (nt) is called long non-coding RNAs (lncRNA). LncRNAs now have been shown to play important epigenetic regulatory roles in key molecular processes, such as gene expression, genetic imprinting, histone modification, chromatin dynamics, and other activities by forming specific structures and interacting with all kinds of molecules. This paper mainly discusses the correlation between the structure and function of lncRNAs with the recent progress in epigenetic regulation, which is important to the understanding of the mechanism of lncRNAs in physiological and pathological processes.

Molecular diagnosis of lymph node metastasis in patients with upper urinary tract cancer who underwent lymphadenectomy.

To determine the significance of molecular diagnosis of lymph node metastasis using quantitative reverse transcription polymerase chain reaction in patients with upper urinary tract urothelial cancer. A total of 51 patients with upper urinary tract urothelial cancer who underwent extended lymphadenectomy were included in the present study. Retrieved lymph nodes from each patient were divided into two parts. One part was assessed by quantitative reverse transcription polymerase chain reaction assay for molecular staging, whereas the other one was assessed by routine histopathological examination. Four kinds of molecules (FXYD3, KRT19, KRT20 and UPK2) were selected as markers to detect urothelial cancer cells. The average number of retrieved lymph nodes was 18.3. As UPK2 showed the best discrimination ability among four markers, the patients were classified in three categories according to UPK2 expression: N(+)PCR(+) for patients who had lymph node metastasis by routine pathological diagnosis as well as quantitative reverse transcription polymerase chain reaction (n = 4); N(-)PCR(+) for patients who had lymph node metastasis by polymerase chain reaction but not by routine pathological diagnosis (n = 7); and N(-)PCR(-) for patients who showed no lymph node metastasis not only by routine pathological diagnosis but also by polymerase chain reaction (n = 40). The prognosis of the N(-)PCR(+) group was better than that of the N(+)PCR(+) group, and similar to that of the N(-)PCR(-) group. Quantitative reverse transcription polymerase chain reaction could detect micrometastasis in patients with upper urinary tract urothelial cancer. However, the prognosis of patients with micrometastasis is better than patients with pathologically metastasized lymph nodes, and similar to patients without micrometastasis.

A Local Extension of the Electrophilicity Index Concept

A local measure of the electrophilicity has been recently proposed to analyze the chemical reactivity of several kinds of molecules. In this work a theoretical rationalization of the local extension is proposed following the quantitative definition of the molecular electrophilic power and a variational method for the distribution of the transferred charge. A condensation scheme to atoms or fragments follows from its relation to the Fukui function and the local softness. Differences between these quantities are discussed and they are tested in a model system. The analysis shows that the local electrophilicity is more appropriate to describe differences among a set of substituted molecules.

Theoretical study on magnetism induced by H vacancy in isolated Alq3 and Gaq3 molecules

The magnetism induced by H vacancy in isolated Alq3 and Gaq3 molecules has been studied based on density functional theory. The isolated stoichiometric Alq3 and Gaq3 molecules are non-magnetic. With an H vacancy, both Alq3 and Gaq3 molecules could show magnetism, which are mainly due to the polarization of the C 2p electrons and the magnetic moments are mainly distributed at most nearby C atoms of H vacancies. This is because the unpaired electron on the C atom appears, when the H atom nearby is removed. Six cases of the H vacancy introduced in the Alq3 and Gaq3 molecules are considered, respectively. By comparing the relative defect formation energy, the VH3 vacancy is most likely to appear in the two kinds of molecules. In addition, for the ground state configuration of isolated Alq3 and Gaq3 molecules with two H vacancies, the energy of the ferromagnetic state is lower than that of the antiferromagnetic state, which means that the ferromagnetic state is stable. The ferromagnetic mechanism can be explained by the Heisenberg direct exchange interaction between two the polarized C atoms. Our work opens a new way to synthesize organic magnetic materials and perfects the theory of organic ferromagnetism by introducing the d0 ferromagnetism.

Nonlocality Induces Chains of Nested Dissipative Solitons.

Dissipative solitons often behave as quasiparticles, and they may form molecules characterized by well-defined bond distances. We show that pointwise nonlocality may lead to a new kind of molecule where bonds are not rigid. The elements of this molecule can shift mutually one with respect to the others while remaining linked together, in a manner similar to interlaced rings in a chain. We report experimental observations of these chains of nested dissipative solitons in a time-delayed laser system.

Derivation of stable Burnett equations for rarefied gas flows.

A set of constitutive relations for the stress tensor and heat flux vector for the hydrodynamic description of rarefied gas flows is derived in this work. A phase density function consistent with Onsager's reciprocity principle and H theorem is utilized to capture nonequilibrium thermodynamics effects. The phase density function satisfies the linearized Boltzmann equation and the collision invariance property. Our formulation provides the correct value of the Prandtl number as it involves two different relaxation times for momentum and energy transport by diffusion. Generalized three-dimensional constitutive equations for different kinds of molecules are derived using the phase density function. The derived constitutive equations involve cross single derivatives of field variables such as temperature and velocity, with no higher-order derivative in higher-order terms. This is remarkable feature of the equations as the number of boundary conditions required is the same as needed for conventional Navier-Stokes equations. Linear stability analysis of the equations is performed, which shows that the derived equations are unconditionally stable. A comparison of the derived equations with existing Burnett-type equations is presented and salient features of our equations are outlined. The classic internal flow problem, force-driven compressible plane Poiseuille flow, is chosen to verify the stable Burnett equations and the results for equilibrium variables are presented.

Targeted Nanoparticles for the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) has a dramatic impact on society. The therapeutic targets are located in the central nervous system (CNS), which limits the efficacy of drugs systemically administered: the blood-brain barrier (BBB) selectively allows the permeation of just a few kinds of molecules from the systemic circulation to the CNS. On the other hand, local administration routes to CNS are highly invasive. In this article, we have reviewed therapeutic approaches against AD, which are based on nanoparticles targeted to the brain and to the pathological hallmarks of the disease. The existing literature has been classified according to the AD feature that is addressed. Nanoparticles have been used for the targeted delivery of drugs aiming to reduce the AD symptoms or to reverse the course of the disease. For this task the multivalency of nanoparticles has allowed their functionalization with several kinds of targeting groups, to cross the BBB and to target the place of treatment. With this approach an increased drug bioavailability has been achieved in the CNS using intravenous administration in place of more invasive administration routes. Additionally, nanoparticles have also been used in the development of vaccines and therapeutic formulations for intranasal administration. Targeted nanoparticles have been proved useful to enhance the performance of therapies against AD in animal models. A better understanding of AD mechanisms will help the successful application of targeted nanoparticles for combined therapies.