Limited Number Of Molecules Research Articles

Antioxidant activity and identification by HPLC-DAD-MS of 3-deoxyanthocyanins in the husks of Sorghum caudatum (L.) Moench grains from Burkina Faso

As indicated by the World Health Organisation (WHO), the resurgence of chronic diseases is projected to account for 70 % of deaths and 56 % of illnesses globally by 2030. In response, authorities are allocating resources towards prevention through the use of substances with natural or synthetic antioxidant properties. However, the safety of synthetic antioxidants is constrained by the limited number of molecules they can be derived from and the necessity for intricate and costly testing to substantiate their safety. In light of this, the scientific community has set itself the objective of identifying new potential sources of natural antioxidants with the more effective capacity in prevetion of these chronic diseases. Anthocyanins, particularly 3-deoxyanthocyanins are cited as one antioxidant molecules with preventive efficacy. The objective of this study is to contribute to the discovery of new sources of 3-deoxyanthocyanins. In order to achieve this objective, a concentrated extract of 3-deoxyanthocyanins was first prepared by maceration of the husks of Sorghum caudatum grains in acidified ethanol, followed by precipitation in acidified distilled water.The Folin-Ciocalteu and differential pH methods were then employed to determine the total phenolic compound content and the total 3-deoxyanthocyanin content of the extract, respectively. The antioxidant potential of the extract was evaluated by determining its free radical scavenging activity using the ABTS method, its reducing power of ferric ions using the FRAP method, and the percentage of hydrogen peroxide (H2O2) scavenging. Using physico-chemical and physical methods (PC, HPLC, UV–vis and MS), the 3-deoxyanthocyanins present in the extract from the husks of Sorghum caudatum grains were identified. The results of these analyses demonstrated that the total phenolic compound content was 237.73 ± 2.12 mg GAE/g extract, while the 3-deoxyanthocyanin content was 99.33 ± 4.16 mg EApi/g extract and 110.05 ± 4.33 mg ELt/g extract. The extract demonstrated notable antioxidant activity, with an CI50 of 62.59 µg/mL as determined by the ABTS method, a content of 77.35 ± 0.17 mg TE /g extract as quantified by the FRAP method, and an H2O2 scavenging percentage of approximately 72.29 %. The extract was found to contain five distinct compounds, namely luteolinidin, 7-O-methylluteolinidin, 5-O-methylluteolinidin, apigeninidin and 7-O-methylapigeninidin. The grain husks of Sorghum caudatum represent a novel source of 3-deoxyanthocyanins. Consequently, they offer a promising avenue for the extraction of natural antioxidants, natural colouring agents and nutraceuticals for the food industry, thereby enhancing the economic value of agricultural waste and augmenting the profitability of Sorghum cultivation.

Probing low-frequency terahertz calculation: A comparison between periodic boundary conditions and cluster models

Terahertz spectroscopy performs as a powerful tool for revealing valuable information on molecular interactions. In recent years, low-frequency terahertz simulation through periodic boundary conditions has proved to be a great success with regard to long-range force and complete noncovalent interaction rather than cluster models or unit cell models. However, quantum chemistry simulation with a limited number of molecules also enables many in-depth and comprehensive analytical methods, therefore, encouraging proving the outcome validity of the cluster models based on quantum chemistry calculation. In this article, we compared the computational results of both periodic boundary conditions and cluster models through solid-state density functional theory, revealing the necessity of a periodic structure in calculating low-frequency terahertz bands, which is instrumental for the selection of computational models for terahertz spectra.

Inducing Singlet Fission in Perylene Thin Films by Molecular Contortion.

Singlet fission occurs only in a limited number of molecules, and expanding the molecular toolbox is necessary for progress. Here, we apply the molecular contortion strategy to tune singlet and triplet energies and observe changes in the excited-state dynamics that are consistent with singlet fission playing a role in thin films of contorted perylene. Perylene is a prototypical molecular chromophore, which does not undergo singlet fission in its planar form from its S1 state. The tuning of the energetics that control singlet fission through molecular contortion can be applied to a large repertoire of established molecular chromophores.

Identification of Candidate MicroRNA-mRNA Subnetwork for Predicting the Osteosarcoma Progression by Bioinformatics Analysis.

Osteosarcoma (OS) is the pretty common primary cancer of the bone among the malignancies in adolescents. A single molecular component or a limited number of molecules is insufficient as a predictive biomarker of OS progression. Hence, it is necessary to find novel network biomarkers to improve the prediction and therapeutic effect for OS. Here, we identified 230 DE-miRNAs and 821 DE-mRNAs through two miRNA expression-profiling datasets and three mRNA expression-profiling datasets. We found that hsa-miR-494 is closely linked with the survival of OS patients. In addition, we analyzed GO and KEGG enrichment for targets of hsa-miR-494-5p and hsa-miR-494-3p through R programming. And five mRNAs were predicted as common targets of hsa-miR-494-5p and hsa-miR-494-3p. We further revealed that upregulated TRPS1 was strongly correlated with poor outcomes in OS patients through the survival analysis based on the TARGET database. The qRT-PCR study verified that the expression of hsa-miR-494-5p and hsa-miR-494-3p was declined considerably, while TRPS1 was notably raised in OS cells when compared to the osteoblasts. Thus, we generated a new regulatory subnetwork of key miRNAs and target mRNAs using Cytoscape software. These results indicate that the novel miRNA-mRNA subnetwork composed of hsa-miR-494-5p, hsa-miR-494-3p, and TRPS1 might be a characteristic molecule for assessing the prognostic value of OS patients.

Expert Systems for Predicting the Bioavailability of Sun Filters in Cosmetic Products, Software vs. Expert Formulator: The Benzophenone-3 Case.

There are only a limited number of molecules in a cosmetic formulation, which can passively cross the stratum corneum and be absorbed into the skin layers. However, some actives should never cross the skin in large concentrations due to their potential for side effects, for example, sunscreens. Artificial intelligence is gaining an increasing role as a predictive tool, and in this regard, we selected the Formulating for Efficacy® Software to forecast the changes in bioavailability of selected topical cosmetic compounds. Using the Franz diffusion cell methodology, various oils were selected as those with low release capability, and these were compared to those suggested by the software in Benzophenone-3-containing formulations. The software was able to predict the lipophilic phases, which, if utilized in the emulsion, were stable and sometimes even more pleasant in appearance and consistency than the reference emulsions prepared by the formulator. To date, however, Formulating for Efficacy® Software still has limitations as far as predicting the hydrophilic phase, as well as not being able to choose the emulsifier or the preservative system.

Current Advances in CETSA.

Knowing that the drug candidate binds to its intended target is a vital part of drug discovery. Thus, several labeled and label-free methods have been developed to study target engagement. In recent years, the cellular thermal shift assay (CETSA) with its variations has been widely adapted to drug discovery workflows. Western blot–based CETSA is used primarily to validate the target binding of a molecule to its target protein whereas CETSA based on bead chemistry detection methods (CETSA HT) has been used to screen molecular libraries to find novel molecules binding to a pre-determined target. Mass spectrometry–based CETSA also known as thermal proteome profiling (TPP) has emerged as a powerful tool for target deconvolution and finding novel binding partners for old and novel molecules. With this technology, it is possible to probe thermal shifts among over 7,000 proteins from one sample and to identify the wanted target binding but also binding to unwanted off-targets known to cause adverse effects. In addition, this proteome-wide method can provide information on the biological process initiated by the ligand binding. The continued development of mass spectrometry labeling reagents, such as isobaric tandem mass tag technology (TMT) continues to increase the throughput of CETSA MS, allowing its use for structure–activity relationship (SAR) studies with a limited number of molecules. In this review, we discussed the differences between different label-free methods to study target engagement, but our focus was on CETSA and recent advances in the CETSA method.

Multi-Omics Characterization of Tumor Microenvironment Heterogeneity and Immunotherapy Resistance Through Cell States-Based Subtyping in Bladder Cancer.

Due to the strong heterogeneity of bladder cancer (BC), there is often substantial variation in the prognosis and efficiency of immunotherapy among BC patients. For the precision treatment and assessment of prognosis, the subtyping of BC plays a critical role. Despite various subtyping methods proposed previously, most of them are based on a limited number of molecules, and none of them is developed on the basis of cell states. In this study, we construct a single-cell atlas by integrating single cell RNA-seq, RNA microarray, and bulk RNA-seq data to identify the absolute proportion of 22 different cell states in BC, including immune and nonimmune cell states derived from tumor tissues. To explore the heterogeneity of BC, BC was identified into four different subtypes in multiple cohorts using an improved consensus clustering algorithm based on cell states. Among the four subtypes, C1 had median prognosis and best overall response rate (ORR), which characterized an immunosuppressive tumor microenvironment. C2 was enriched in epithelial-mesenchymal transition/invasion, angiogenesis, immunosuppression, and immune exhaustion. Surely, C2 performed the worst in prognosis and ORR. C3 with worse ORR than C2 was enriched in angiogenesis and almost nonimmune exhaustion. Displaying an immune effective environment, C4 performed the best in prognosis and ORR. We found that patients with just an immunosuppressive environment are suitable for immunotherapy, but patients with an immunosuppressive environment accompanied by immune exhaustion or angiogenesis may resist immunotherapy. Furthermore, we conducted exploration into the heterogeneity of the transcriptome, mutational profiles, and somatic copy-number alterations in four subtypes, which could explain the significant differences related to cell states in prognosis and ORR. We also found that PD-1 in immune and tumor cells could both influence ORR in BC. The level of TGFβ in a cell state can be opposite to the overall level in the tissues, and the level in a specific cell state could predict ORR more accurately. Thus, our work furthers the understanding of heterogeneity and immunotherapy resistance in BC, which is expected to assist clinical practice and serve as a supplement to the current subtyping method from a novel perspective of cell states.

Making sense of neural development by comparing wiring strategies for seeing and hearing.

The ability to perceive and interact with the world depends on a diverse array of neural circuits specialized for carrying out specific computations. Each circuit is assembled using a relatively limited number of molecules and common developmental steps, from cell fate specification to activity-dependent synaptic refinement. Given this shared toolkit, how do individual circuits acquire their characteristic properties? We explore this question by comparing development of the circuitry for seeing and hearing, highlighting a few examples where differences in each system's sensory demands necessitate different developmental strategies.

Serological landscape of cytokines in cutaneous melanoma.

To date, serological markers to monitor melanoma progression and response to therapy are lacking. In this context cytokines appear to be promising biomarkers of the disease. To compare cytokine and chemokine levels in melanoma patients and in healthy controls and to assess possible variations according to melanoma stage. Serum chemokine and cytokine levels were determined by ELISA in 34 patients diagnosed histologically of malignant melanoma. Seven healthy volunteers were used as controls. We found a subset of cytokines (CCL3, CCL4, IFN-γ and IL-10) to be significantly higher in melanoma patients than in control group, thus confirming the importance of the inflammation in cancer. While CCL3 increased with tumor progression, IFN-γ and IL-10 showed higher levels in stage I patients. Moreover, we noticed a direct correlation between CCL3 level and the presence of ulceration in the primary tumor; on the contrary, CCL4, IL-10 and IFN-γ were lowered down in patients with ulcerated melanoma. These results expand and confirm observations made in other studies focusing on a more limited number of molecules. This extended panel of cytokines examines the potential roles of type2 cytokines (such as IL-4) and many chemokines (mainly CCL3) as biomarkers in melanoma progression.

Molecular discovery by optimal sequential search

In the development of a new compound in chemistry and molecular biology, especially a new medicine in pharmaceutical industry, we often need to find candidate(s), a molecule or molecules, with the best desired property (e.g., binding affinity in medicine) from a large set of molecules with the same scaffold but m distinct functional substitutes at each of its n different sites. The total number $$N_{\mathrm{lib}}$$ of molecules in this library is $$m^n$$ . In some cases, $$N_{\mathrm{lib}}$$ can be a very large number (e.g., millions). This is a challenging task because it is costly and often infeasible to synthesize and test all of these molecules. A new algorithm referred to as optimal sequential search is developed to overcome this difficulty. Especially, this algorithm is chemically intuitive which only uses the information of molecule composition, and accessible to practical chemists. The algorithm can be applied to small, medium and large size molecule libraries. With syntheses and property measurements for a limited number of molecules, the top best candidate molecules can be effectively captured from the whole library. Three examples with library size 64, 160,000 and 1,048,576, respectively, are used for illustration. For the first small library, syntheses and property measurements of 17 molecules are sufficient to capture the top 7 best candidate molecules; for the two medium and large libraries, syntheses and property measurements of about one thousand molecules can capture most or a large part of the top 500, especially the top 100 best candidate molecules. However, the algorithm needs to perform multiple (e.g., hundreds of) iterative syntheses and property measurements. The time cost may not be acceptable if the algorithm is performed manually. To make the algorithm practical, automation of the sequential searching process is the following task.

A nonextensive approach for understanding the van der Waals’ equation

In order to improve the teaching of statistical physics in universities, in this article we introduce nonextensive statistics, a new statistical theory about complex systems. We study the two modification coefficients a and b in the van der Waals’ equation in nonextensive statistics and thus understand the possible relation between the van der Waals’ equation and the nonextensivity. We express these coefficients when a real gas is regarded as the nonextensive gas and then relate them to the q-parameter in nonextensive statistics. Furthermore, we derive the q-parameter of a real gas, which contains the intermolecular Lennard-Jones potential, but also strongly depends on the state parameter and molecular number of the gas. From the new statistical physics, we show that the nonextensivity plays a significant role in the coefficients of the van der Waals’ equation if the gas contains a limited number of molecules or the gas is regarded as a few-body system. This article is aimed at senior undergraduate students, graduate students and those who teach statistical physics in universities.

Superhydrophobic hierarchically structured surfaces in biology: evolution, structural principles and biomimetic applications.

A comprehensive survey of the construction principles and occurrences of superhydrophobic surfaces in plants, animals and other organisms is provided and is based on our own scanning electron microscopic examinations of almost 20 000 different species and the existing literature. Properties such as self-cleaning (lotus effect), fluid drag reduction (Salvinia effect) and the introduction of new functions (air layers as sensory systems) are described and biomimetic applications are discussed: self-cleaning is established, drag reduction becomes increasingly important, and novel air-retaining grid technology is introduced. Surprisingly, no evidence for lasting superhydrophobicity in non-biological surfaces exists (except technical materials). Phylogenetic trees indicate that superhydrophobicity evolved as a consequence of the conquest of land about 450 million years ago and may be a key innovation in the evolution of terrestrial life. The approximate 10 million extant species exhibit a stunning diversity of materials and structures, many of which are formed by self-assembly, and are solely based on a limited number of molecules. A short historical survey shows that bionics (today often called biomimetics) dates back more than 100 years. Statistical data illustrate that the interest in biomimetic surfaces is much younger still. Superhydrophobicity caught the attention of scientists only after the extreme superhydrophobicity of lotus leaves was published in 1997. Regrettably, parabionic products play an increasing role in marketing.This article is part of the themed issue 'Bioinspired hierarchically structured surfaces for green science'.

The Unifying Nature of Basic Science Research.

Why does research matter? Why do professional scientists choose to spend their careers working on specific topics, and what impact does this have on society and the people (largely taxpayers) who fund the research enterprise? Is the public investment in many diverse areas of fundamental research really worth it? These are questions that I have asked myself throughout my career as I have progressed from student to research fellow to head of an academic laboratory. My experience has convinced me of the value of broad-based, highly diverse basic research. Like most molecular biologists, in my early training I was exposed to a wide variety of experimental systems, from mammalian cell culture to fruit flies to mice. While I found all of these models interesting and well worth studying, it was when I was first exposed to the complex interplay between pathogens and their hosts that I became utterly captivated. In particular, I was fascinated by the intricate methods pathogens use to systematically vary the proteins they expose to their host’s immune system, a process referred to as antigenic variation. Virtually all pathogens that are able to maintain chronic infections have evolved the ability to display only a limited number of molecules that the host is able to recognize and target for the development of an immune response. Then, just when the immune system begins to gain the upper hand and eliminate the infection, the pathogen changes its surface coat and displays an entirely new set of antigens that the host must respond to; thus, the whole process starts again. Many of these pathogens maintain large repertoires of genes that encode these “disguises,” utilizing a complex process of coordinated gene activation and silencing that enables them to slowly reveal each variant one at a time over the course of an infection. As a research subject, this topic has many interesting angles: coevolution of two organisms, complex networks of gene expression, antigen recognition and diversification, to name a few. Once this game of molecular “hide and seek” between host and pathogen was revealed to me, I was hooked, and I have continued to work on this topic throughout my career. Our work to understand the mechanisms underlying antigenic variation in eukaryotic pathogens has led us to many of the same molecular processes that have recently been discovered in the study of eukaryotic model systems. For example, many of the gene regulatory mechanisms, in particular epigenetic processes, that higher eukaryotes utilize to control gene expression during cellular differentiation are used by parasites and pathogenic fungi to control the expression of the genes encoding variant surface antigens. In higher eukaryotes, these epigenetic modifications are often part of the terminal differentiation process and, thus, are typically permanent, while in pathogens the changes are reversible, thereby enabling them to switch genes on and off and adding a clever twist to the story. I am fascinated by the parallels in the molecular mechanisms employed by both host and pathogen to regulate gene expression. Working in this field has brought me back to the early days of my training as a molecular biologist when my studies focused on model eukaryotic systems, and today I am just as likely to read a paper about zebra fish as I am about malaria parasites, the focus of my research. The shared mechanisms of epigenetic gene regulation employed both by higher eukaryotic organisms (including humans) and infectious pathogens reminds us of the unifying nature of fundamental, basic research in the biological sciences. Concepts deciphered through studies of yeast, fruit flies, slime molds, or the simple worm Caenorhabditis elegans can have profound implications for our understanding of human biology or the pathogens that infect us. This synergism between fields of study greatly increases the pace of discovery in all systems and provides a reminder that, as scientists, we are all on the same team. As a researcher works diligently to understand a key aspect underlying how a cell in a fruit fly becomes part of a leg versus an antenna, he or she might be making a key discovery that will influence the development of a novel drug to treat malaria, a disease that kills hundreds of thousands of children annually. The march of science is unpredictable, and it is often difficult to imagine where the next breakthrough will come from. Nonetheless, we can be sure that diverse, fundamental, basic science will continue to improve the lives of people all over the planet, just as it has for centuries. In my mind, this is why research matters. Image 1 Kirk W. Deitsch.

1/F α-Type Noise in Lead Sulfide-Based Photosensitive Elements

Of all the different types of infrared radiation photodetectors, only photoresistors based on lead sulfide PbS possess a variety of different methods and technologies of fabrication. This is because the first photoresistors were fabricated before the development of the theory of photoconductivity in monocrystals and, second, because of the failures which developers of photodetectors based on monocrystalline structures had experienced. The high absorption factor (10 4 cm ‐1 ) [1] suggested the use of thin (1‐2 µm) layers, whereas production of monocrystalline layers by an epitaxial method is possible only at high concentrations of the majority carriers (p ≥ 10 17 cm ‐3 ), which led to a decrease in the life of the carriers. Often, such films are considered to be nonphotosensitive, since the life of the carriers becomes less than their flight time to contact. Polycrystalline films that are suitable for the fabrication of photodetectors are one alternative. Methods of producing these types of films are provisionally divided into chemical methods based on reactions between acetic lead Pb(CH 3 COO) 2 , thiocarbamide (NH 2 ) 2 CS, caustic soda, and other reduction-oxidation agents, and physical methods, in which the primary PbS layer is deposited in a vacuum by means of thermal deposition. In most of the technologies employed, the layer is then annealed in a muffle furnace, oxygen (which is an acceptor impurity) then being introduced into the film. In certain cases, a technique of redeposition of layers in a vacuum with one photodetector layer on top of another is used, as a result of which a layer entraps only the limited number of molecules of oxygen necessary for increasing the life of the vacancies. Successes in the development of photodetectors based on polycrystalline films functioning at a frequency of 400‐1000 Hz have made it possible to solve urgent problems. In the transition from monocrystalline to polycrystalline layers, the mobility of the carriers falls 100-fold (with increasing dark resistance), with 1/F α -type noise becoming dominant over

Identification of potential biomarkers of hepatitis B-induced acute liver failure using hepatic cells derived from human skin precursors

Besides their role in the elucidation of pathogenic processes of medical and pharmacological nature, biomarkers can also be used to document specific toxicological events. Hepatic cells generated from human skin-derived precursors (hSKP-HPC) were previously shown to be a promising in vitro tool for the evaluation of drug-induced hepatotoxicity. In this study, their capacity to identify potential liver-specific biomarkers at the gene expression level was investigated with particular emphasis on acute liver failure (ALF). To this end, a set of potential ALF-specific biomarkers was established using clinically relevant liver samples obtained from patients suffering from hepatitis B-associated ALF. Subsequently, this data was compared to data obtained from primary human hepatocyte cultures and hSKP-HPC, both exposed to the ALF-inducing reference compound acetaminophen. It was found that both in vitro systems revealed a set of molecules that was previously identified in the ALF liver samples. Yet, only a limited number of molecules was common between both in vitro systems and the ALF liver samples. Each of the in vitro systems could be used independently to identify potential toxicity biomarkers related to ALF. It seems therefore more appropriate to combine primary human hepatocyte cultures with complementary in vitro models to efficiently screen out potential hepatotoxic compounds.

Surface Amplification of L-Glutamate Using a Patterned Bienzymatic System for Biosensing Applications

Electronic sensing of neurotransmitter molecules is based on a diffusion-limited process, which requires the immobilization of biological recognition elements as close as possible to the active area of the sensor. Moreover, in many applications, the analyte concentration is very low. In particular, the in situ detection of neurotransmitter release from neurons is challenging due to the limited number of molecules secreted and their fast diffusion and reuptake immediately after release. In this paper, we present a method that allows for the local amplification of L-glutamate directly on the chip surface. Our approach is based on the surface patterning of a bienzymatic system consisting of glutamate oxidase (GLOD) and glutamic-pyruvate transaminase (GPT) that amplifies L-glutamate via a recycling process. The surface chemistry was optimized for maximal enzyme loading. The level of amplification was determined using a colorimetric assay. Coimmobilization of GLOD and GPT yielded at least a doubling of the signal, and increasing the surface concentrations of each enzyme led to amplification levels that approached those obtained in solution. We show that these enzymes can be patterned on substrates using a flip chip bonder for aligned microcontact printing. Furthermore, primary mouse hippocampal neurons were successfully cultured on these patterned surfaces and remained viable for at least five days. The enzymatic pattern was preserved on the substrate surface for the same time period. Lastly, amplification of L-glutamate released from neurons seven days in vitro was detected. Thus, we conclude that this bienzymatic system can ultimately be applied to biosensor surfaces for the in vitro detection of L-glutamate.

Cryogenic zone compression for the measurement of dioxins in human serum by isotope dilution at the attogram level using modulated gas chromatography coupled to high resolution magnetic sector mass spectrometry

A liquid nitrogen jet-cooled thermal modulator dedicated to comprehensive two-dimensional gas chromatography has been mounted in a GC oven coupled to a high resolution magnetic sector mass spectrometry instrument. The data acquisition parameters of the slow double-focusing magnetic sector MS instrument have been optimized to accommodate the description of the narrow modulated GC peaks. Acquisition rates were increased to 20 Hz, while maintaining high mass resolution. Selected ion monitoring (SIM) descriptors, typically including several ions for both native and labeled analytes, were thus reduced to one or two to ensure enough MS cycle time. For maximization of the sensitivity enhancement due to cryogenic zone compression (CZC), the entire GC peak of interest was trapped and remobilized in one event. Optimization of the method resulted in the ability to detect low attogram (ag) amounts of 2,3,7,8-tetrachlorodibenzo- p-dioxin (2,3,7,8-TCDD) (313 ag gives a S/N of 400:1), a level that had not yet been attained using classical GC–HRMS. An isotope-dilution calibration curve was constructed using 13C 12-2,3,7,8-TCDD as the internal standard over the range of 500 ag/μL to 35,000 ag/μL ( R 2 = 0.9953). Analyses of a standard natural human reference serum-matrix NIST SRM 1589a containing 223 ag of 1,2,3,7,8-pentachlorodibenzo- p-dioxin (1,2,3,7,8-PeCDD) (70% recovery rate assumed) resulted in a peak with a S/N of 188:1 (4 sigma, m/ z = 355.8546). Measurement of 2,2-bis (4-chlorophenyl-1,1,1-trichloroethane) (DDE) and 2,2′,4,4′,5,5′-hexabromobiphenyl (BB-153) in human dried-blood spot (DBS) samples is also reported to illustrate the usefulness of such a sensitive technique. Finally, some of the challenges related to sample preparation, blank levels, and to the fact of measuring of such a limited number of molecules (less than 600,000 TCDD molecules) are discussed.

SlC30A8 Is a Major Target of Humoral Autoimmunity in Type 1 Diabetes and a Predictive Marker in Prediabetes

Type 1A diabetes (T1D) results from autoimmunity targeted at a limited number of molecules that are expressed in the pancreatic beta cell. Putative novel autoantigen candidates were identified from microarray expression profiling of human and rodent islet cells. The highest ranking candidate was Slc30A8 (zinc transporter 8; ZnT8), which was screened by radioimmunoprecipitation assays against new-onset T1D and prediabetic sera. Such assays detected 63% of subjects with new-onset diabetes, but fewer than 2% of controls, 3% of those with type 2 diabetes, and 10% of patients with other autoimmune disorders. ZnT8 autoantibodies were found, however, in 26% of T1D subjects previously classified as autoantibody-negative on the basis of existing markers (GADA, IA2 A, IAA, and ICA). We conclude that SLC30A8 provides an important additional and independent predictive marker for T1D.

Time Fluctuations and Imaging in the SERS Spectra of Fungal Hypha Grown on Nanostructured Substrates

Surface-enhanced Raman scattering (SERS) spectroscopy is an emerging technique in biomolecular analysis that can have a tremendous impact in the life sciences. We report on the SERS imaging of fungal hyphae grown on nanostructured SERS active substrates engineered using semiconductor technologies. Time fluctuations in the intensity and band position in the SERS spectra measured on the same sample position with 1 s integration time have been observed indicating that the SERS signal arises from a limited number of molecules and that possibly single components are being detected.

The electrochemical behavior of a system with a limited number of molecules

In this paper, based on Einstein relationship between diffusion and random walk, the electrochemical behavior of a system with a limited number of molecules was simulated and explored theoretically. The transition of the current vs time responses from discrete to continuous was clearly obtained as the number of redox molecules increased from 10 to 106. By correlation analysis between the simulation results and the results of analytical expressions, a quantized extent parameter was proposed to investigate the underlying rules of these discrete signals, which looked stochastic. The results revealed that this parameter would be useful to describe such systems.