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Plain language summary: Biomarkers may offer unforeseen insights into clinical diagnosis, as well as the likely course and outcome of a condition. In this paper, the focus is on the use of biological molecules found in body fluids or tissues for diagnosis and prediction of outcome in ovarian cancer patients. In cancer care, biomarkers are being used to develop personalised treatment plans for patients based on the unique characteristics of their tumour. This tailoring of care can be used to pursue specific targets identified by biomarkers, or treat the patient according to specific tumour characteristics. Surgery is one of the core treatments for ovarian cancer, whether it is offered in primary surgery or following chemotherapy in delayed surgery. Biomarkers already exist to guide the treatment of tumours with chemotherapy, but very little research has determined the value of biomarkers in tailoring surgical care for ovarian cancer. Such research is required to identify new biomarkers and assess their effectiveness in a clinical setting as well as to help identify specific tumour types to guide surgery. Biomarkers could help to determine the success of removing the disease surgically, or help to identify tumour deposits that persist after chemotherapy. All of these aspects would improve current practice. This Scientific Impact Paper highlights research that may pave the way towards bespoke surgery according to the biological characteristics of a tumour and aid gynaecological oncologists to provide surgical treatment according to individual need, rather than a blanket approach for all. [ABSTRACT FROM AUTHOR]

Abstract: A novel ultra‐low‐cost biochemical analysis platform to quantify protein dissociation binding constants and kinetics using paper microfluidics is reported. This approach marries video imaging with one of humankind's oldest materials: paper, requiring no large, expensive laboratory equipment, complex microfluidics or external power. Temporal measurements of nanoparticle–antibody conjugates binding on paper is found to follow the Langmuir Adsorption Model. This is exploited to measure a series of antibody–antigen dissociation constants on paper, showing excellent agreement with a gold‐standard benchtop interferometer. The concept is demonstrated with a camera and low‐end smartphone, 500‐fold cheaper than the reference method, and can be multiplexed to measure ten reactions in parallel. These findings will help to widen access to quantitative analytical biochemistry, for diverse applications spanning disease diagnostics, drug discovery, and environmental analysis in resource‐limited settings. [ABSTRACT FROM AUTHOR]

To circumvent the bottlenecks of non-flexibility, low sensitivity, and narrow workable detection range of conventional biosensors for biological molecule detection (e.g., dopamine (DA) secreted by living cells), a new hybrid flexible electrochemical biosensor has been created by decorating closely packed dendritic Pt nanoparticles (NPs) on freestanding graphene paper. This innovative structural integration of ultrathin graphene paper and uniform 2D arrays of dendritic NPs by tailored wet chemical synthesis has been achieved by a modular strategy through a facile and delicately controlled oil-water interfacial assembly method, whereby the uniform distribution of catalytic dendritic NPs on the graphene paper is maximized. In this way, the performance is improved by several orders of magnitude. The developed hybrid electrode shows a high sensitivity of 2 μA cm−2 μ m−1, up to about 33 times higher than those of conventional sensors, a low detection limit of 5 n m, and a wide linear range of 87 n m to 100 μ m. These combined features enable the ultrasensitive detection of DA released from pheochromocytoma (PC 12) cells. The unique features of this flexible sensor can be attributed to the well-tailored uniform 2D array of dendritic Pt NPs and the modular electrode assembly at the oil-water interface. Its excellent performance holds much promise for the future development of optimized flexible electrochemical sensors for a diverse range of electroactive molecules to better serve society. [ABSTRACT FROM AUTHOR]

Tracing heavy metals is a crucial issue in both environmental and medical samples. In this work, a sensing biomolecule, the cyanobacterial C-phycocyanin (CPC), is integrated into a nanocellulose matrix, and with this, a biosensor for copper ions is developed. The assembly of CPC-functionalized nanocellulose into a red-fluorescent, copper-sensitive hybrid film 'CySense', enhances protein stability and facilitates the reuse and the regeneration of the sensor for several cycles over 7 days. CySense is suitable for the analysis of complex medical samples such as human serum filtrate. The reported biosensor reliably detects copper ion contents with a lower detection limit of 200 × 10−9 m and an IC50 of 4.9 × 10−6 m as changes in fluorescence emission intensity that can be measured with a fluorimeter or a microarray laser scanner. [ABSTRACT FROM AUTHOR]

A simple method is described for the patterned deposition of Teflon on paper to create an integrated platform for parallel organic synthesis and cell-based assays. Solvent-repelling barriers made of Teflon-impregnated paper confine organic solvents to specific zones of the patterned array and allow for 96 parallel flow-through syntheses on paper. The confinement and flow-through mixing significantly improves the peptide yield and simplifies the automation of this synthesis. The synthesis of 100 peptides ranging from 7 to 14 amino acids in length gave over 60 % purity for the majority of the peptides (>95 % yield per coupling/deprotection cycle). The resulting peptide arrays were used in cell-based screening to identify 14 potent bioactive peptides that support the adhesion or proliferation of breast cancer cells in a 3D environment. In the future, this technology could be used for the screening of more complex phenotypic responses, such as cell migration or differentiation. [ABSTRACT FROM AUTHOR]

As biological macromolecules, proteins are involved in important cellular functions ranging from DNA replication and biosynthesis to metabolic signalling and environmental sensing. Protein sequencing can help understand the relationship between protein function and structure, and provide key information for disease diagnosis and new drug design. Nanopore sensors are a novel technology to achieve the goal of label‐free and high‐throughput protein sequencing. In recent years, nanopore‐based biosensors have been widely used in the detection and analysis of biomolecules such as DNA, RNA, and proteins. At the same time, computer simulations can describe the transport of proteins through nanopores at the atomic level. This paper reviews the applications of nanopore sensors in protein sequencing over the past decade and the solutions to key problems from a computer simulation perspective, with the aim of pointing the way to the future of nanopore protein sequencing. [ABSTRACT FROM AUTHOR]

In this paper, a dielectric modulated negative capacitance (NC) MoS2 FET‐based biosensor is proposed for label‐free detection of biomolecules such as enzymes, proteins, DNA, and so forth. Various reports present on experimental demonstration and modeling of NC MoS2 FET but it is never utilized as a dielectric modulated biosensor. So, in this work, the modeling, characterization and sensitivity analysis of dielectric modulated NC MoS2 FET is focused. For immobilization of biomolecules, a nanocavity is formed below the gate by etching some portion of the gate oxide material. The immobilization of biomolecules in the cavity leads to a variation of different electrostatic properties such as surface potential, threshold voltage, drain current, and subthreshold swing which can be utilized as sensing parameters. An analytical model for the proposed biosensor is also developed in the subthreshold region by considering the properties of two‐dimensional ferroelectric materials and benchmarked with TCAD device simulations. The effect of change of gate length and doping concentration on different electrical properties is also analyzed to estimate the optimum value of channel doping. The results prove that the proposed device can be used for next‐generation low power label‐free biosensor which shows enhanced sensitivity as compared to traditional FET‐based biosensors. [ABSTRACT FROM AUTHOR]

Key Laboratory for Ultrafine Materials of Ministry of Education Centre for Biomedical Technologies Current tissue engineering technology aims to achieve the regeneration of human tissues, which integrates the key factors such as scaffolds, cells and biomolecules. Among these key factors, the development of high‐performance scaffolds is the basis for the success of tissue engineering strategies. In the past decades, hydrogel scaffolds have been developed rapidly and widely used in biomedical field, however, their drawbacks have also been revealed, which shows that a single hydrogel scaffold cannot meet the excellent performance required in the field of tissue engineering. Recently, microspheres have been further engineered to fabricate structurally and functionally reliable artificial three‐dimensional scaffolds of desired shape with enhanced specific biological functions. Therefore, the effective combination of hydrogel and microspheres can facilitate the development of high‐performance scaffolds for tissue engineering and further fine‐tuning the composite structure, which is expected to solve the dilemma faced by a single scaffold. In this review paper, we systematically summurized the type and preparation method for synthesis of hydrogel and microsphere materials commonly used in developing microsphere‐containing hydrogel scaffolds. We then reviewed the broad application of these hybrid scaffolds in various fields of tissue engineering, followed by a summary and perspective on future directions. [ABSTRACT FROM AUTHOR]

Presents a list of articles for publication in future issues of the "European Journal of Biochemistry". Conformation of physalaemin; Association of cross-linked proteins with a specific mRNA in the cytoplasm of HeLa cells; Transport of proteins into chloroplasts.

There are places in our planet where environmental conditions are beyond normal limits for growth but still harbour life. Extremophile microalgae are the candidates for large‐scale production because (i) their extreme growth conditions help to avoid unwanted contaminations, facilitating their production and (ii) in order to survive under harsh environments, these microorganisms synthesise valuable uncommon biomolecules. Extremophile microalgae include Arthrospira platensis, used as a source of phycocyanin and produced under highly alkaline conditions, and Dunaliella salina, which is industrially produced as a source of β‐carotene and can naturally resist salinity conditions exceeding 300 g L−1. Microalgae can be produced on non‐arable lands, using seawater, and within a wide range of environmental conditions, allowing their production in almost any part of the planet. The current paper aimed at highlighting the biotechnological potential of extremophile microalgae as sources for carotenoids, valuable molecules used as pigments and health‐promoters. [ABSTRACT FROM AUTHOR]

This paper presents a device ("fluidic biomill") and method for integrated mechanical structuring and biofunctionalization of microfluidic channels, enabling rapid prototyping of biochips. The fluidic biomill leverages hydrodynamic flow confinements (HFCs) to localize the interaction between a fluid and a substrate to a microscale region. By confining organic solvents, and scanning with the biomill over the substrate surface, microchannels as deep as 90 µm are fluidically milled. Subsequently, by switching the confined fluid from a milling solution to a patterning solution, biomolecules are immobilized on the surface of the microchannel. An in‐depth analysis of fluidic milling rates and milled microchannel properties is presented, along with a discussion on the dominant factors in controlling the dimensions of the fluidically milled channel. To demonstrate the utility of this method, a biotin functionalized biochip is fabricated in less than 5 min out of a polystyrene slide and its functionalities are validated by implementing on‐chip electrokinetic sample focusing, pressure driven flow, and a surface‐based reaction. [ABSTRACT FROM AUTHOR]

The article presents information on various research papers which will be published in the forthcoming issue of the "European Journal of Biochemistry". Some of the papers discusses are "Enzymatic Synthesis of Neolactotetraosylceramide by the N-Acctyllactosamine Synthase of Human Serum". "Rate of Transplantation and Kinetics of Processing of Newly Synthesized Molecules of Two Major Outer-Membrane Proteins, the OmpA and OmpF Proteins of Escherichia Coli," by the researchers I. Crowlesmith and K. Gamon.

This article presents a list of some of the forthcoming papers in biochemistry to be published in this journal. Some of the papers listed are "The Organization of the Chloroplast DNA in wheat and maize in the region containing the LS Gene," by B. Koller, H. Delius and T.A. Dyer, "Effect of Carbamination on the Buffering Power of Purified Human Hamoglobins A Solutions At Two Temperatures," by M. Castaing, E. Bursaux and C. Poyart, "The Complete Nucleotide of the Chicken Ovotransferrin mRNA," by J.M. Jeltsch and P. Chambon, "The Primary Structure of Hen Ovotransferrin," by J. Williams, T.C. Elleman, I.B. Kington, A.G. Wilkins and K.A. Kuhn.

As a promising candidate for rapid and ultrasensitive sensing of biomolecules, terahertz time‐domain spectroscopy (THz‐TDS) can be considered with superior performance in label‐free, noncontact, noninvasive, and nondestructive detection. In particular, almost significant conformational information can be captured with THz‐TDS. Meanwhile, terahertz (THz) metamaterial or metasurface biosensing chips based on THz‐TDS were proposed to promote the detection sensitivity within strong local field‐matter enhancement. In this paper, the ultrasensitive THz biosensing metamaterial and metasurface for DNA/RNA detecting based on spoof surface plasmon polaritons (SSPPs) is probed. The simulated results show that the maximum frequency sensitivity of the proposed metamaterial and metasurface for DNA/RNA biosensing can respectively approach to 2.52 THz/refractive index unit (RIU) and 2.23 THz/RIU. In addition, the film thickness sensitivities of metamaterial and metasurface biosensors are respectively higher than 71.1 GHz/μm and 79.2 GHz/μm when the thickness of biomaterial is thinner than 4 μm. All these ascendant performances achieved in the proposed metamaterial and metasurface biosensors can be realized and exploited for ultrasensitive biomolecules detection, health monitoring, medical film sensing, and safety inspection in THz regime. [ABSTRACT FROM AUTHOR]

Royal jelly (RJ) is secretion from the hypopharyngeal glands of worker bees, which serves as food for the queen bee and enabling larvae growth. Having biological properties already proven, RJ has considerable commercial appeal and is used in many sectors (pharmacy, food industries, and cosmetic products) nowadays. However, due to its chemical complexity on one hand and the easy adulteration and sensitivity of the biological molecules present, a limited information of the Raman spectrum of RJ is available, although it has been methodically investigated by midinfrared spectroscopy. The present paper aims to systematize the previous petite Raman spectroscopy knowledge and to holistically grasp band assignments in the whole region in Raman spectrum by fabrication of Ag nanoparticles (AgNPs) with surface adsorbed RJ. In order to obtain representative Raman spectrum in which the bands of the major components in the RJ (proteins and sugars) could be forced to appear here, AgNP‐RJ particles are fabricated. The method enabled to enhance the weak Raman signal, decreased the fluorescence, and improved signal‐to‐noise ratio. The obtained AgNPs with RJ were synthesized by careful selection of three stabilizing water‐soluble agents (citrate, poly (ethylene glycol), and polyvinylpyrrolidone) and produced SERS effect that increased the Raman bands signal and allowed, for the first time, to interpret the whole Raman spectrum of RJ. [ABSTRACT FROM AUTHOR]

In this paper, we report the regioselective synthesis of 3,5‐disubstituted isoxazoles by 1,3‐dipolar cycloaddition between alkynyl dipolarophiles and nitrile oxide dipoles generated in‐situ from O‐silylated hydroxamic acids in the presence of trifluoromethanesulfonic anhydride and NEt3. Thanks to the mild, metal‐free and oxidant‐free conditions that this strategy offers, the reaction was successfully applied to a wide variety of alkynyl dipolarophiles, demonstrating the tolerance of this approach to diverse functional groups. In particular, we have shown that the method was compatible with biological molecules such as peptides and peptide nucleic acids (PNA). This protocol constitutes another example of metal‐free 1,3‐dipolar cycloaddition leading to the regioselective formation of isoxazoles. [ABSTRACT FROM AUTHOR]

Single‐site multifunctionalization of glycans is of importance in biological studies considering its crucial role in mediating biological events and human diseases. In this paper, a novel approach for multifunctional labelling of glycans has been developed featuring the use of fluorescence resonance energy transfer‐based (FRET‐based) probes for fluorescent labelling of glycans through a gold(III)‐mediated three‐component coupling reaction. Oxidation of glycans into aldehydes followed by the A3‐coupling reaction with FRET‐based probes resulted in the single‐site formation of fluorescent propargylamine products. The conversion of labelled glycans can be revealed by ratiometric analysis of the FRET signals. This labelling approach results in multifunctionalization of glycans with high selectivity and conversion between 66 and 69 %. [ABSTRACT FROM AUTHOR]

The hexose monophosphate (HMP) shunt acts as an essential component of cellular metabolism in maintaining carbon homeostasis. The HMP shunt comprises two phases viz. oxidative and nonoxidative, which provide different intermediates for the synthesis of biomolecules like nucleotides, DNA, RNA, amino acids, and so forth; reducing molecules for anabolism and detoxifying the reactive oxygen species during oxidative stress. The HMP shunt is significantly important in the liver, adipose tissue, erythrocytes, adrenal glands, lactating mammary glands and testes. We have researched the articles related to the HMP pathway, its metabolites and disorders related to its metabolic abnormalities. The literature for this paper was taken typically from a personal database, the Cochrane database of systemic reviews, PubMed publications, biochemistry textbooks, and electronic journals uptil date on the hexose monophosphate shunt. The HMP shunt is a tightly controlled metabolic pathway, which is also interconnected with other metabolic pathways in the body like glycolysis, gluconeogenesis, and glucuronic acid depending upon the metabolic needs of the body and depending upon the biochemical demand. The HMP shunt plays a significant role in NADPH2 formation and in pentose sugars that are biosynthetic precursors of nucleic acids and amino acids. Cells can be protected from highly reactive oxygen species by NADPH 2. Deficiency in the hexose monophosphate pathway is linked to numerous disorders. Furthermore, it was also reported that this metabolic pathway could act as a therapeutic target to treat different types of cancers, so treatments at the molecular level could be planned by limiting the synthesis of biomolecules required for proliferating cells provided by the HMP shunt, hence, more experiments still could be carried out to find additional discoveries. [ABSTRACT FROM AUTHOR]

Acquisition of X‐ray crystallographic data is always accompanied by structural degradation owing to the absorption of energy. The application of high‐fluency X‐ray sources to large biomolecules has increased the importance of finding ways to curtail the onset of X‐ray‐induced damage. A significant effort has been under way with the aim of identifying strategies for protecting protein structure. A comprehensive model is presented that has the potential to explain, both qualitatively and quantitatively, the structural changes induced in crystalline protein at ∼100 K. The first step is to consider the qualitative question: what are the radiation‐induced intermediates and expected end products? The aim of this paper is to assist in optimizing these strategies through a fundamental understanding of radiation physics and chemistry, with additional insight provided by theoretical calculations performed on the many schemes presented. [ABSTRACT FROM AUTHOR]

The European X‐ray Free‐Electron Laser (FEL) became the first operational high‐repetition‐rate hard X‐ray FEL with first lasing in May 2017. Biological structure determination has already benefitted from the unique properties and capabilities of X‐ray FELs, predominantly through the development and application of serial crystallography. The possibility of now performing such experiments at data rates more than an order of magnitude greater than previous X‐ray FELs enables not only a higher rate of discovery but also new classes of experiments previously not feasible at lower data rates. One example is time‐resolved experiments requiring a higher number of time steps for interpretation, or structure determination from samples with low hit rates in conventional X‐ray FEL serial crystallography. Following first lasing at the European XFEL, initial commissioning and operation occurred at two scientific instruments, one of which is the Single Particles, Clusters and Biomolecules and Serial Femtosecond Crystallography (SPB/SFX) instrument. This instrument provides a photon energy range, focal spot sizes and diagnostic tools necessary for structure determination of biological specimens. The instrumentation explicitly addresses serial crystallography and the developing single particle imaging method as well as other forward‐scattering and diffraction techniques. This paper describes the major science cases of SPB/SFX and its initial instrumentation – in particular its optical systems, available sample delivery methods, 2D detectors, supporting optical laser systems and key diagnostic components. The present capabilities of the instrument will be reviewed and a brief outlook of its future capabilities is also described. [ABSTRACT FROM AUTHOR]

The Adaptive Gain Integrating Pixel Detector (AGIPD) is an X‐ray imager, custom designed for the European X‐ray Free‐Electron Laser (XFEL). It is a fast, low‐noise integrating detector, with an adaptive gain amplifier per pixel. This has an equivalent noise of less than 1 keV when detecting single photons and, when switched into another gain state, a dynamic range of more than 104 photons of 12 keV. In burst mode the system is able to store 352 images while running at up to 6.5 MHz, which is compatible with the 4.5 MHz frame rate at the European XFEL. The AGIPD system was installed and commissioned in August 2017, and successfully used for the first experiments at the Single Particles, Clusters and Biomolecules (SPB) experimental station at the European XFEL since September 2017. This paper describes the principal components and performance parameters of the system. A description of the 1 million pixel AGIPD system in use at the SPB beamline of the European XFEL is given. [ABSTRACT FROM AUTHOR]

Abstract: Diarylethene derivatives, the biological activity of which can be reversibly changed by irradiation with light of different wavelengths, have shown promise as scientific tools and as candidates for photocontrollable drugs. However, examples demonstrating efficient photocontrol of their biological activity are still relatively rare. This concept article discusses the possible reasons for this situation and presents a critical analysis of existing data and hypotheses in this field, in order to extract the design principles enabling the construction of efficient photocontrollable diarylethene‐based molecules. Papers addressing biologically relevant interactions between diarylethenes and biomolecules are analyzed; however, in most published cases, the efficiency of photocontrol in living systems remains to be demonstrated. We hope that this article will encourage further discussion of design principles, primarily among pharmacologists, synthetic and medicinal chemists. [ABSTRACT FROM AUTHOR]

Abstract: Sepiolite is a nanofibrous natural silicate that can be used as a nanocarrier for DNA transfer thanks to its strong interaction with DNA molecules and its ability to be naturally internalized into mammalian cells through both non‐endocytic and endocytic pathways. Sepiolite, due to its ability to bind various biomolecules, could be a good candidate for use as a nanocarrier for the simultaneous vectorization of diverse biological molecules. In this paper, we review our recent work, issued from a starting collaboration with Prof. Ruiz‐Hitzky, that includes diverse aspects on the characterization and main features of sepiolite/DNA nanohybrids, and we present an outlook for the further development of sepiolite for DNA transfer. [ABSTRACT FROM AUTHOR]

Abstract: Gold plasmonic nanostructures with high sensitivity and spectral reproducibility are key components of molecular sensors based on surface‐enhanced Raman scattering (SERS). In this paper, we report a “bottom‐up” fabrication of gold “film over nanosphere” (FON) substrates for SERS sensing on the basis of very small (107 nm in diameter) polystyrene spheres coated with 20 nm of gold. To obtain close‐packed spheres in a large scale area, the self‐assembly at the water–air interface was found to be very efficient. Sensitivity and reproducibility of the AuFON substrates were tested using various molecular probes: 5,10,15,20‐tetrakis(1‐methyl‐4‐pyridyl)porphyrin, p‐aminothiophenol, and benzocaine. Relative standard deviation of SERS signal was found to be less than 20% confirming good spectral reproducibility especially using a 100× objective. Then, we demonstrated sensitive SERS detection of other biologically important molecules adsorbed on our AuFON substrates: thiolated‐polyA, protoporphyrin IX, and two alkaloids (nicotine and strychnine). Estimated limits of detection were 8.2 × 10−7 and 4.5 × 10−7 M (in order of 100 ng.ml−1) incubation concentration for strychnine and nicotine, respectively. Therefore, we conclude that the 20‐nm gold film deposited on polystyrene spheres of 107 nm in diameter provided both good spectral reproducibility and sensitivity. Their implementation into the SERS‐active system will enable to bring about new quantitative and analytical SERS applications. [ABSTRACT FROM AUTHOR]

Vibrational circular dichroism (VCD) has become a standard method for determination of absolute stereochemistry, particularly now that reliable commercial instrumentation has become available. These instruments use a now well-documented Fourier transform infrared-based approach to measure VCD that has virtually displaced initial dispersive infrared-based designs. Nonetheless, many papers have appeared reporting dispersive VCD data, especially for biopolymers. Instrumentation designed with these original methods, particularly after more recent updates optimizing performance in selected spectral regions, has been shown still to have advantages for specific applications. This article presents a mini-review of dispersive VCD instrument designs and includes sample spectra obtained for various biopolymer (particularly peptide) samples. Complementary reviews of Fourier transform-VCD designs are broadly available. [ABSTRACT FROM AUTHOR]

Abstract: Modification of nucleic acids with osmium tetroxide reagents (Os,L, such as OsO4,2,2′‐bipyridine, Os,bpy) has been applied in redox DNA labeling, in probing DNA structure as well as in studies of DNA interactions with other molecules. In natural DNA, primarily thymine residues form adducts with the Os,bpy in a structure selective manner. In this paper we introduce a new two‐step technique of DNA modification with the electroactive Os,bpy, consisting in enzymatic construction of DNA bearing butyl acrylate (BA) moieties attached to uracil at C5 or to 7‐deaza adenine at C7, followed by chemical modification of a reactive C=C double bond in the acrylate residue. We demonstrate a facile modification of the BA conjugates in both single‐ and double‐stranded (ds) DNA under conditions when modification within the nucleobase rings in ds DNA is hindered. Various DNA−Os,bpy adducts can easily be analyzed electrochemically and distinguished by different redox potentials. The two‐step procedure appears to be applicable in osmium redox labelling of ds DNA. [ABSTRACT FROM AUTHOR]

The article presents graphical abstracts of papers published within the issue, including one on copper corroles, another on metal-biomolecule frameworks and a paper on magnetic complexes.

SUMMARY Recently, the structure, function, stability, and dynamics of subcellular structures, organelles, and multiprotein complexes have emerged as a leading interest in structural biology. Geometric modeling not only provides visualizations of shapes for large biomolecular complexes but also fills the gap between structural information and theoretical modeling, and enables the understanding of function, stability, and dynamics. This paper introduces a suite of computational tools for volumetric data processing, information extraction, surface mesh rendering, geometric measurement, and curvature estimation of biomolecular complexes. Particular emphasis is given to the modeling of cryo-electron microscopy data. Lagrangian-triangle meshes are employed for the surface presentation. On the basis of this representation, algorithms are developed for surface area and surface-enclosed volume calculation, and curvature estimation. Methods for volumetric meshing have also been presented. Because the technological development in computer science and mathematics has led to multiple choices at each stage of the geometric modeling, we discuss the rationales in the design and selection of various algorithms. Analytical models are designed to test the computational accuracy and convergence of proposed algorithms. Finally, we select a set of six cryo-electron microscopy data representing typical subcellular complexes to demonstrate the efficacy of the proposed algorithms in handling biomolecular surfaces and explore their capability of geometric characterization of binding targets. This paper offers a comprehensive protocol for the geometric modeling of subcellular structures, organelles, and multiprotein complexes. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Metal-organic frameworks (MOFs) as chemical sensors have developed rapidly in recent years. There have been many papers concerning this field and interest is still growing. The reason is that the specific merits of MOFs can be utilized to enhance sensitivity and selectivity by various energy/charge transfers occurring among different ligands, ligand, and metal centers, such as from ligands to metal centers or metal centers to ligands, as well as from MOF skeletons to guest species. This review intends to provide an update on recent progress in various applications of different MOF-based sensors on the basis of their luminescent and electrochemical responses towards small molecules, gas molecules, ions (cations and anions), pH, humidity, temperature, and biomolecules. MOF-based sensors function by utilizing different mechanisms, including luminescent responses of 'turn-on' and 'turn-off', as well as electrochemical responses. [ABSTRACT FROM AUTHOR]

The article present abstracts of various papers that were presented during the Scandinavian Physiological Society meeting titled "Transport and Membrane Trafficking in Cells" that was held form May 7-9, 2004 at Goteborg University, Lundsbrunn Spa. One of the papers discussed is "Trafficking of Ion Transport Proteins: New Partners and Potential Therapies," by M.J. Caplan, A. Duffield, E. Kamsteeg, J. Gloeckner-Pagel and M.E. Egan. The physiologic function of an ion transport protein is determined, in part, by its subcellular localization and by the cellular mechanisms that modulate its activity. The authors are interested in the molecular signals and interactions that control the sorting and regulation of ion transport proteins in polarized cells. Another paper discussed is "Receptor Dynamics at Synapses: A View From Single Molecule Imaging," by A. Triller.

In this paper we report the synthesis of new azabicycloalkane scaffolds, which could be exploited to obtain cRGD-based bioconjugates that may find promising application for targeted drug delivery, theranostic, and general cancer-cell labeling. By exploiting a Hosomi-Sakurai intramolecular allylation reaction we efficiently converted a silylated aldehyde precursor into 7,5-fused lactam scaffolds endowed with an exocyclic double bond. The presence of the vinyl function should make it possible to conjugate bioactive compounds to selectively carry them to tumor sites. The optimized synthetic sequence allows the gram-scale preparation of the target scaffolds in a few steps and good 39% overall yield from readily accessible materials. The high reactivity of the exocyclic olefin moiety was ascertained by performing a Heck coupling reaction with 1-bromo-4-nitrobenzene, which gave the corresponding functionalized derivatives in good (80-91%) yields. [ABSTRACT FROM AUTHOR]

The first aim of this paper is to review recent progress in identifying genes in plants homologous to cell division cycle (cdc) genes of fission yeast. In the latter, cdc genes are well-characterised. Arguably, most is known about cdc2 which encodes a 34 kDa protein kinase (p34cdc2) that functions at the G2-M and G1-S transition points of the cell cycle. At G2-M, the p34cdc2 protein kinase is regulated by a number of gene products that function in independent regulatory pathways. The cdc2 kinase is switched on by a phosphatase encoded by cdc25, and switched off by a protein kinase encoded by wee1. p34 Must also bind with a cyclin protein to form maturation promoting factor before exhibiting protein kinase activity. In plants, homologues to p34cdc2 have been identified in pea, wheat, Arabidopsis, alfalfa, maize and Chlamydomonas. They all exhibit the PSTAIRE motif, an absolutely conserved amino acid sequence in all functional homologues sequenced so far. As in animals, some plant species contain more than one cdc2 protein kinase gene, but in contrast to animals where one functions at G2-M and the other (CDK2 in humans and Eg1 in Xenopus) at G1-S, it is still unclear whether there are functional differences between the plant p34cdc2 protein kinases. Again, whereas in animals cyclins are well characterised on the basis of sequence analysis, into class A, class B (G2-M) and CLN (G1 cyclins), cyclins isolated from several plant species cannot be so clearly characterised. The differences between plant and animal homologues to p34cdc2 and cyclins raises the possibility that some of the regulatory controls of the plant genes may be different from those of their animal counterparts. The second aim of the paper is to review how planes of cell division and cell size are regulated at the molecular level. We focus on reports showing that p34cdc2 binds to the preprophase band (ppb) in late G2 of the cell cycle. The binding of p34cdc2 to ppbs may be important in regulating changes in directional growth but, more importantly, there is a requirement to understand what controls the positioning of ppbs. Thus, we highlight work resolving proteins such as the microtubule associated proteins (MAPs) and those mitogen activated protein kinases (MAP kinases), which act on, or bind to, mitotic microtubules. Plant homologues to MAP kinases have been identified in alfalfa. Finally, some consideration is given to cell size at division and how alterations in cell size can alter plant development. Transgenic tobacco plants expressing the fission yeast gene, cdc25, exhibited various perturbations of development and a reduced cell size at division. Hence, cdc25 affected the cell cycle (and as a consequence, cell size at division) and cdc25 expression was correlated with various alterations to development including precocious flowering and altered floral morphogenesis. Our view is that the cell cycle is a growth cycle in which a cell achieves an optimal size for division and that this size control has an important bearing on differentiation and development. Understanding how cell size is controlled, and how plant cdc genes are regulated, will be essential keys to ‘the cell cycle locks’, which when ‘opened’, will provide further clues about how the cell cycle is linked to plant development. [ABSTRACT FROM AUTHOR]

1. Sequence analysis of the NADPH domain (residues 158 - 293) and of the interface domain (365 - 478) was based on 12 CNBr fragments, which were isolated using ion-exchange chromatography and paper methods. Fragments with more than 15 residues were digested further with trypsin and chymotrypsin. The isolated peptides were sequenced by automated solid-phase Edman degradation. All sequenced peptides were ordered and overlapped by computerized comparisons with a complete sequence guessed from the electron density map of the protein. In the case of short CNBr fragments, this alignment was confirmed by the sequence analysis of protein fragments resulting from incomplete CNBr cleavage. 2. In the NADPH domain, residue 197, which is involved in an induced-fit mechanism, was identified as a tyrosine. The structure of the NADPH domain is probably homologous with the NAD domain of lipoamide dehydrogenase and with the FAD domain of several proteins, but not with NADPH domains of known chainfold in other proteins. 3. The paper completes the sequence analysis of glutathione reductase so that the enzyme is now known in atomic detail. The numbering scheme of the chemically determined sequence will be used henceforth in crystallographic studies also. As inferred from the sequence data each of the two identical chains contains 478 amino acid residues, the composition being Cys10, Asp21, Asn17, Thr31, Ser31, Glu29, Gln11, Pro24, Gly43, Ala42, Val44, Met15, Ile29, Leu34, Tyr13, Phe14, Lys34. His16, Arg17, and Trp3. From these data an mr of 2 × 51 600 was calculated for the FAD-free apoenzyme and an Mr of 2 × 52400 for the holoenzyme. [ABSTRACT FROM AUTHOR]

This paper is a further study of ion binding to protein surfaces and builds on the studies of the binding of [Crk(CN)6]3- and [Fe(edta)(H2O)]- previously reported [Williams et al. (1982) FEBS Lett. 15, 293-299; Eley et al. (1982) Eur. J. Biochem. 124, 295-303]. In the present paper the binding of polyaminocarboxylate complexes of gadolinium have been studied. Eight ion-binding sites have been identified on the surface of cytochrome c. These exhibit different binding specificities which, in some cases, are not fully understood. However it is clear that simple outer-sphere interactions are not the sole determining factor for the association of metal ion complexes with proteins. The NMR paramagnetic difference spectrum method has been shown to be good at locating binding sites and revealing qualitative differences in their relative affinities for a range of complex types. However the use of relaxation probes is not a good method for the quantitative determination of binding constants; for this, isostructural shift probes must be sought. [ABSTRACT FROM AUTHOR]

The poor recovery of large biomolecules is a well-known issue in reversed-phase liquid chromatography. Several papers have reported this problem, but the reasons behind this behavior are not yet fully understood. In the present study, state-of-the-art reversed-phase wide-pore stationary phases were used to evaluate the adsorption of therapeutic monoclonal antibodies. These biomolecules possess molar mass of approximately 150 000 g/mol and isoelectric points between 6.6 and 9.3. Two types of stationary phases were tested, the Phenomenex Aeris Widepore (silica based), with 3.6 μm superficially porous particles, and the Waters Acquity BEH300 (ethylene-bridged hybrid), with 1.7 μm fully porous particles. A systematic investigation was carried out using 11 immunoglobulin G1, G2, and G4 antibodies, namely, panitumumab, natalizumab, cetuximab, bevacizumab, trastuzumab, rituximab, palivizumab, belimumab, adalimumab, denosumab, and ofatumumab. All are approved by the Food and Drug Administration and the European Medicines Agency in various therapeutic indications and are considered as reference antibodies. Several test proteins, such as human serum albumin, transferrin, apoferritin, ovalbumin, and others, possessing a molar mass between 42 000 and 443 000 g/mol were also evaluated to draw reliable conclusions. The purpose of this study was to find a correlation between the adsorption of monoclonal antibodies and their physicochemical properties. Therefore, the impact of isoelectric point, molar mass, protein glycosylation, and hydrophobicity was investigated. The adsorption of intact antibodies on the stationary phase was significantly higher than that of proteins of similar size, isoelectric point, or hydrophobicity. The present study also demonstrates the unique behavior of monoclonal antibodies, contributing some unwanted and unpredictable strong secondary interactions. [ABSTRACT FROM AUTHOR]

In this review paper, we present several examples of reactive molecular dynamics simulations, which contribute to a better understanding of the underlying mechanisms in plasma medicine on the atomic scale. This includes the interaction of important reactive oxygen plasma species with the outer cell wall of both gram-positive and gram-negative bacteria, and with lipids present in human skin. Moreover, as most biomolecules are surrounded by a liquid biofilm, the behavior of these plasma species in a liquid (water) layer is presented as well. Finally, a perspective for future atomic scale modeling studies is given, in the field of plasma medicine in general, and for cancer treatment in particular. [ABSTRACT FROM AUTHOR]

N-Acetylneuraminic acid (sialic acid, Neu5Ac) has recently gained interest as a potential marker for a variety of pathophysiological processes, although no Raman study has been reported for this important biomolecule. In this paper, the vibrational properties of Neu5Ac were studied by means of Raman, surface-enhanced Raman scattering (SERS), and density functional theory calculations. By adsorption of Neu5Ac on silver nanoparticle surface, strongly enhanced Raman intensities are obtained, allowing easy measurement of small amounts of aqueous Neu5Ac (10 µl of a 10−7 m solution) utilizing low laser power and short exposure time. The mechanism of adsorption of Neu5Ac on the silver surface is discussed on the basis of the experimental and theoretical results. This study demonstrates that SERS can provide an effective tool for development of a label-free, rapid, and sensitive optical platform for identification of Neu5Ac. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Among the variety of transducer concepts proposed for label-free detection of biomolecules, the semiconductor field-effect device (FED) is one of the most attractive platforms. As medical techniques continue to progress towards diagnostic and therapies based on biomarkers, the ability of FEDs for a label-free, fast and real-time detection of multiple pathogenic and physiologically relevant molecules with high specificity and sensitivity offers very promising prospects for their application in point-of-care and personalized medicine for an early diagnosis and treatment of diseases. The presented paper reviews recent advances and current trends in research and development of different FEDs for label-free, direct electrical detection of charged biomolecules by their intrinsic molecular charge. The authors are mainly focusing on the detection of the DNA hybridization event, antibody-antigen affinity reaction as well as clinically relevant biomolecules such as cardiac and cancer biomarkers. [ABSTRACT FROM AUTHOR]

The phenylbenzothiazole compounds show antitumor properties and are highly selective. In this paper, the 99Tc chemical shifts based on the (99mTc)(CO)3(NNO) complex conjugated to the antitumor agent 2-(4′-aminophenyl)benzothiazole are reported. Thermal and solvent effects were studied computationally by quantum-chemical methods, using the density functional theory (DFT) (DFT level BPW91/aug-cc-pVTZ for the Tc and BPW91/IGLO-II for the other atoms) to compute the NMR parameters for the complex. We have calculated the 99Tc NMR chemical shifts of the complex in gas phase and solution using different solvation models (polarizable continuum model and explicit solvation). To evaluate the thermal effect, molecular dynamics simulations were carried, using the atom-centered density matrix propagation method at the DFT level (BP86/LanL2dz). The results highlight that the 99Tc NMR spectroscopy can be a promising technique for structural investigation of biomolecules, at the molecular level, in different environments. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The Escherichia coli division protein FtsQ, which plays a central role in the septosome assembly, interacts with several protein partners of the division machinery. Its interaction with FtsB and FtsL allows the formation of the trimeric complex connecting the early cytoplasmic cell division proteins with the late, essentially periplasmic, ones. Little is known about the interactions that FtsQ contracts with other divisome components, besides the fact that all are localized in its periplasmic domain. In this domain, two independent subdomains, both involved in FtsQ, FtsI and FtsN interactions, were also identified. The study of FtsQ interaction-defective mutants constituted a basis to investigate the biological significance of its interactions. However, in the case of interactions where two independent sites are involved, mutation(s) in one domain can be suppressed by the presence of the still-functional second interaction region. To ascertain the biological role of these interactions, it is therefore necessary to select double mutants, where both sites are impaired. This paper describes the behaviour of FtsQ double mutants that have lost the ability to interact with FtsN, which is the last component in the hierarchy of divisome assembly, and is necessary to guarantee its stability and function. [ABSTRACT FROM AUTHOR]

Superparamagnetic particles have been attractive for molecular diagnostics and analytical chemistry applications due to their unique magnetic properties and their ability to interact with various biomolecules of interest. This paper presents a critical overview of magnetic nano - and microparticles used as a solid phase for extraction and purification of DNAs. The mechanisms of DNA binding to the surface of functionalised magnetic particles are described. The most widely used materials including silica supports, organic polymers and other materials, mostly containing magnetite or paramagnetic metallic elements are reviewed. The main application areas of magnetic particles for DNA separation are briefly described. [ABSTRACT FROM AUTHOR]

Synthetic biology is first represented in terms of two complementary aspects, the bio-engineering one, based on the genetic manipulation of extant microbial forms in order to obtain forms of life which do not exist in nature; and the chemical synthetic biology, an approach mostly based on chemical manipulation for the laboratory synthesis of biological structures that do not exist in nature. The paper is mostly devoted to shortly review chemical synthetic biology projects currently carried out in our laboratory. In particular, we describe: the minimal cell project, then the “Never Born Proteins” and lastly the Never Born RNAs. We describe and critically analyze the main results, emphasizing the possible relevance of chemical synthetic biology for the progress in basic science and biotechnology. [ABSTRACT FROM AUTHOR]

This paper outlines recent advances in the integration of enzyme-based biocomputing systems operating as Boolean logic gates and their networks with various bioelectronic devices. 'Smart' switchable electrodes for biosensors and biofuel cells with built-in biomolecular logic were designed. Interfacing between the biocomputing systems and switchable electrodes resulted in bioelectronic devices controlled by complex patterns of variable biomolecular signals. Various biomedical applications of the novel logically-controlled bioelectronic devices are feasible. [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THE SUBJECT • Ciclosporin's nephrotoxicity initially targets the proximal tubule and is, at least in part, driven by increased formation of oxygen radicals. • 1H-nuclear magnetic resonance spectroscopy (NMR)- and mass spectrometry (MS)-based biochemical profiling (metabolomics) allows for the sensitive detection of metabolite pattern changes in urine. • In systematic studies in rats we showed that ciclosporin caused urine metabolite pattern changes typical for proximal tubule damage and that these pattern changes seemed to be more sensitive than established clinical kidney function markers such as serum creatinine concentrations. WHAT THIS PAPER ADDS • This study showed that urine metabolite pattern changes as assessed by 1H-NMR and HPLC-MS are sensitive enough to detect the effect of ciclosporin as early as 4 h after a single oral dose. • In our previous rat studies, changes in urine metabolite pattern in response to ciclosporin translated into healthy humans, indicating the involvement of the same toxicodynamic mechanisms. • The results provide proof of concept for further development of this combination molecular marker strategy into diagnostic tools for the detection and monitoring of drug nephrotoxicity. AIMS The immunosuppressant ciclosporin is an efficient prophylaxis against transplant organ rejection but its clinical use is limited by its nephrotoxicity. Our previous systematic studies in the rat indicated urine metabolite pattern changes to be sensitive indicators of the negative effects of ciclosporin on the kidney. To translate these results, we conducted an open label, placebo-controlled, crossover study assessing the time-dependent toxicodynamic effects of a single oral ciclosporin dose (5 mg kg−1) on the kidney in 13 healthy individuals. METHODS In plasma and urine samples, ciclosporin and 15- F2t-isoprostane concentrations were assessed using HPLC-MS and metabolite profiles using 1H-NMR spectroscopy. RESULTS The maximum ciclosporin concentrations were 1489 ± 425 ng ml−1 (blood) and 2629 ± 1308 ng ml−1 (urine). The increase in urinary 15- F2t-isoprostane observed 4 h after administration of ciclosporin indicated an increase in oxidative stress. 15- F2t-isoprostane concentrations were on average 2.9-fold higher after ciclosporin than after placebo (59.8 ± 31.2 vs. 20.9 ± 19.9 pg mg−1 creatinine, P < 0.02). While there were no conclusive changes in plasma 15- F2t-isoprostane concentrations or metabolite patterns, non-targeted metabolome analysis using principal components analysis and partial least square fit analysis revealed significant changes in urine metabolites typically associated with negative effects on proximal tubule cells. The major metabolites that differed between the 4 h urine samples after ciclosporin and placebo were citrate, hippurate, lactate, TMAO, creatinine and phenylalanine. CONCLUSION Changes in urine metabolite patterns as a molecular marker are sufficiently sensitive for the detection of the negative effects of ciclosporin on the kidney after a single oral dose. [ABSTRACT FROM AUTHOR]

Many biological molecules carry a net surface charge and have the potential to be monitored in drinking water by electrodepositing them on an optical sensing element and measuring their spectroscopic fingerprints in the infrared (IR) spectral region. In this detection scheme, glasses with high conductivity and excellent IR transmitting property are essential. Therefore, it is necessary to develop suitable materials that combine these properties. In this paper, a series of high-conductivity IR transmitting glasses in Ge–As–Te and Ge–As–Te–Cu systems are reported. The conductivity, thermal stability, IR transmitting property, as well as chemical durability are studied. Their suitability for bio-optical detection applications is also evaluated. Some glasses in these two systems have relatively high conductivities (near 10−4 (Ω·cm)−1), and exhibit superior thermal stability, excellent IR transmitting property, as well as good chemical durability. The electro-deposition and spectroscopic tests of protein molecules indicate that these glasses are promising materials for bio-optical detection applications. [ABSTRACT FROM AUTHOR]

High-abundant plasma proteins pose a challenge in a large number of proteomics-based technologies. Depletion of these high-abundant proteins has proven to be a fruitful strategy to circumvent masking of lower-abundant proteins that could serve as valuable biomarker candidates. However, current strategies often do not meet the throughput requirements of large-scale proteomic studies. In the present paper, a flexible and parallelized method for the depletion of high-abundant proteins is described, allowing the removal of the two most abundant proteins from 48 blood-derived samples in less than 15 min using Affibody molecules as affinity ligands. A sample-processing platform like this should be suitable for a number of proteomics technologies; its flexibility in buffer composition allows for different types of downstream applications. [ABSTRACT FROM AUTHOR]

This paper describes the influence of nitrate availability on growth and release of dissolved free and combined carbohydrates (DFCHOs and DCCHOs) produced by Spondylosium pygmaeum (Cooke) W. West (Zygnematophyceae). This strain was isolated from a subtropical shallow pond, located at the extreme south of Brazil (Rio Grande, RS). Experiments were carried out in batch culture, comparing two initial nitrate levels (10/100 μM) in the medium. Growth was monitored by direct microscopic cell counts and chl a content. Nitrate consumption was determined by ion chromatography, while the production of extracellular carbohydrates was monitored by the phenol-sulfuric method. The monosaccharide compositions of DFCHOs and DCCHOs were determined in each growth phase by HPLC with pulse amperometric detection (HPLC-PAD). At the end of the experiment, the total composition of extracellular polysaccharide (EPS) molecules >12 kDa was determined by gas chromatography. Nitrate availability had no influence on S. pygmaeum cell density at any phase. On the other hand, chl a content decreased after a few days growth when the availability of nitrate was restricted, but continued to rise when nitrate was plentiful. Also, nitrate depletion was faster at 10 μM nitrate. No influence of the growth phase or nitrate availability on the total carbohydrates (TDCHOs) released per cell was observed. Only DCCHOs were released by S. pygmaeum, and the composition varied between growth phases, especially at lower nitrate availability. EPS molecules >12 kDa were composed mainly of xylose, fucose, and galactose, as for other desmids. However, a high N-acetyl-glucosamine content was found, uniquely among desmid EPSs. [ABSTRACT FROM AUTHOR]

The aim of this paper is to relate morphological properties of single biomacromolecules based on molecular enclosing forms indexed by an appropriate form lattice to the symmetry of the crystal where the molecules are periodically packed. Similar to the way in which the 'molécule intégrante' of Haüy permitted a molecular interpretation of the law of rational indices of crystal growth forms, alternative molecular enclosing forms, indexed by a so‐called packing lattice, allow one to bridge the gap between form and crystal lattices. In this first part, selected tutorial examples illustrate the validity of the approach and the crystallographic compatibility between molecular and crystal structures. In particular, integral molecular lattices are shown to imply the observed axial ratios between crystal lattice parameters, leading sometimes to surprising results, like a cubic crystal lattice with a unit cell having a trigonal molecular filling with hexagonal enclosing form. [ABSTRACT FROM AUTHOR]

This paper summarises how scaffold proteins affects and regulate the JNK signalling pathway. We believe that some of these scaffold proteins, by virtue of their anchoring and catalytic properties contribute to a high degree of specificity of intra cellular signalling pathways that regulate the progression through the cell cycle. [ABSTRACT FROM AUTHOR]

In this paper, crystal growth of calcium carbonate CaCO3 in the presence of biomolecules of lotus root was investigated. Scanning electron microscopy, Fourier transform infrared spectroscopy and Xray powder diffractometry were used to characterize the products. The results indicate that calcite spherical particles were constructed from small rhombohedral subunits. Similar CaCO3crystals were also gained when crystal growth of CaCO3in aqueous solution containing extracts of lotus root was performed, suggesting that the soluble biomolecules of lotus root play a crucial role in directing the formation of hierarchical calcite spherical particles. The possible formation mechanism of the CaCO3crystals by using lotus root is also discussed, which can be interpreted by particleaggregation based nonclassical crystallization laws. The biomolecules of lotus root might induce and control the nucleation and growth of calcium carbonate crystals. © 2009 WILEYVCH Verlag GmbH & Co. KGaA, Weinheim [ABSTRACT FROM AUTHOR]