Miracle-dz/UniFAR-FTUs huggingface dataset:
New insights into a classic aptamer: binding sites, cooperativity and more sensitive adenosine detection

Abstract The DNA aptamer for adenosine (also for AMP and ATP) is a highly conserved sequence that has recurred in a few selections. It it a widely used model aptamer for biosensor development, and its nuclear magnetic resonance structure shows that each aptamer binds two AMP molecules. In this work, each binding site was individually removed by rational sequence design, while the remaining site still retained a similar binding affinity and specificity as confirmed by isothermal titration calorimetry. The thermodynamic parameters of binding are presented, and its biochemical implications are discussed. The number of binding sites can also be increased, and up to four sites are introduced in a single DNA sequence. Finally, the different sequences are made into fluorescent biosensors based on the structure-switching signaling aptamer design. The one-site aptamer has 3.8-fold higher sensitivity at lower adenosine concentration with a limit of detection of 9.1 μM adenosine, but weaker fluorescence signal at higher adenosine concentrations, consistent with a moderate cooperativity in the original aptamer. This work has offered insights into a classic aptamer for the relationship between the number of binding sites and sensitivity, and a shorter aptamer for improved biosensor design.
CpG and methylation-dependent DNA binding and dynamics of the methylcytosine binding domain 2 protein at the single-molecule level

Abstract The methylcytosine-binding domain 2 (MBD2) protein recruits the nucleosome remodeling and deacetylase complex (NuRD) to methylated DNA to modify chromatin and regulate transcription. Importantly, MBD2 functions within CpG islands that contain 100s to 1000s of potential binding sites. Since NuRD physically rearranges nucleosomes, the dynamic mobility of this complex is directly related to function. In these studies, we use NMR and single-molecule atomic force microscopy and fluorescence imaging to study DNA binding dynamics of MBD2. Single-molecule fluorescence tracking on DNA tightropes containing regions with CpG-rich and CpG-free regions reveals that MBD2 carries out unbiased 1D diffusion on CpG-rich DNA but subdiffusion on CpG-free DNA. In contrast, the protein stably and statically binds to methylated CpG (mCpG) regions. The intrinsically disordered region (IDR) on MBD2 both reduces exchange between mCpG sites along the DNA as well as the dissociation from DNA, acting like an anchor that restricts the dynamic mobility of the MBD domain. Unexpectedly, MBD2 binding to methylated CpGs induces DNA bending that is augmented by the IDR region of the protein. These results suggest that MBD2 targets NuRD to unmethylated or methylated CpG islands where its distinct dynamic binding modes help maintain open or closed chromatin, respectively.
Dynamic O-GlcNAc cycling at promoters of Caenorhabditis elegans genes regulating longevity, stress, and immunity

Nutrient-driven O-GlcNAcylation of key components of the transcription machinery may epigenetically modulate gene expression in metazoans. The global effects of GlcNAcylation on transcription can be addressed directly in C. elegans because knockouts of the O-GlcNAc cycling enzymes are viable and fertile. Using anti-O-GlcNAc ChIP-on-chip whole-genome tiling arrays on wild-type and mutant strains, we detected over 800 promoters where O-GlcNAc cycling occurs, including microRNA loci and multigene operons. Intriguingly, O-GlcNAc-marked promoters are biased toward genes associated with PIP3 signaling, hexosamine biosynthesis, and lipid/carbohydrate metabolism. These marked genes are linked to insulin-like signaling, metabolism, aging, stress, and pathogen-response pathways in C. elegans. Whole-genome transcriptional profiling of the O-GlcNAc cycling mutants confirmed dramatic deregulation of genes in these key pathways. As predicted, the O-GlcNAc cycling mutants show altered lifespan and UV stress susceptibility phenotypes. We propose that O-GlcNAc cycling at promoters participates in a molecular program impacting nutrient-responsive pathways in C. elegans, including stress, pathogen response, and adult lifespan. The observed impact of O-GlcNAc cycling on both signaling and transcription in C. elegans has important implications for human diseases of aging, including diabetes and neurodegeneration.
Soft Conductive Elastomer Materials for Stretchable Electronics and Voltage Controlled Artificial Muscles

Block copolymer elastomer conductors (BEC) are mixtures of block copolymers grafted with conducting polymers, which are found to support very large strains, while retaining a high level of conductivity. These novel materials may find use in stretchable electronics. The use of BEC is demonstrated in a capacitive strain sensor and in an artificial muscle of the dielectric elastomer actuator type, supporting more than 100% actuation strain and capacity strain sensitivity up to 300%.
Bacterial translation elongation factor EF-Tu interacts and colocalizes with actin-like MreB protein

We show that translation initiation factor EF-Tu plays a second important role in cell shape maintenance in the bacterium Bacillus subtilis. EF-Tu localizes in a helical pattern underneath the cell membrane and colocalizes with MreB, an actin-like cytoskeletal element setting up rod cell shape. The localization of MreB and of EF-Tu is interdependent, but in contrast to the dynamic MreB filaments, EF-Tu structures are more static and may serve as tracks for MreB filaments. In agreement with this idea, EF-Tu and MreB interact in vivo and in vitro. Lowering of the EF-Tu levels had a minor effect on translation but a strong effect on cell shape and on the localization of MreB, and blocking of the function of EF-Tu in translation did not interfere with the localization of MreB, showing that, directly or indirectly, EF-Tu affects the cytoskeletal MreB structure and thus serves two important functions in a bacterium.
Efficacy of ST-246 versus lethal poxvirus challenge in immunodeficient mice

The threat of smallpox as a bioweapon and the emerging threat of human monkeypox, among other poxviral diseases, highlight the need for effective poxvirus countermeasures. ST-246, which targets the F13L protein in vaccinia virus and its homologs in other orthopoxvirus species, provides full protection from lethal poxviral disease in numerous animal models and seems to be safe in humans. All previous evaluations of ST-246 efficacy have been in immunocompetent animals. However, the risk of severe poxviral disease is greater in immunodeficient hosts. Here we report on the efficacy of ST-246 in preventing or treating lethal poxviral disease in immunodeficient mice. After lethal challenge with the Western Reserve strain of vaccinia, Nude, SCID, and JH knockout mice additionally depleted of CD4+ and CD8+ T cells were not fully protected by ST-246, although survival was significantly extended. However, CD4+ T cell deficient, CD8+ T cell deficient, JH knockout, and JH knockout mice also deficient for CD4+ or CD8+ T cells survived lethal challenge when treated with ST-246 starting on the day of challenge. Delaying treatment until 72 h after infection reduced ST-246 efficacy in some models but provided full protection from lethal challenge in most. These findings suggest that ST-246 may be effective in controlling smallpox or other pathogenic orthopoxviruses in some immunodeficient human populations for whom the vaccine is contraindicated.
Electrolyte‐Gated Transistors for Organic and Printed Electronics

Here we summarize recent progress in the development of electrolyte‐gated transistors (EGTs) for organic and printed electronics. EGTs employ a high capacitance electrolyte as the gate insulator; the high capacitance increases drive current, lowers operating voltages, and enables new transistor architectures. Although the use of electrolytes in electronics is an old concept going back to the early days of the silicon transistor, new printable, fast‐response polymer electrolytes are expanding the potential applications of EGTs in flexible, printed digital circuits, rollable displays, and conformal bioelectronic sensors. This report introduces the structure and operation mechanisms of EGTs and reviews key developments in electrolyte materials for use in printed electronics. The bulk of the article is devoted to electrical characterization of EGTs and emerging applications.
Commentary: coeliac disease, mortality and malignancy

Tio and colleagues are to be commended for their ambitious meta-analysis on coeliac disease, death, malignancy and lymphoid malignancy. As shown by most earlier original studies, the overall excess mortality was low in coeliac disease; and patients with coeliac disease do not seem to be at increased risk of ‘any malignancy’. Although a positive association between coeliac disease and lymphoid malignancy is confirmed, it should be remembered that this malignancy is still rare in absolute terms. On three points I had, however, hoped that the authors would take their research even further.
A comprehensive, cell specific microRNA catalogue of human peripheral blood

Abstract With this study, we provide a comprehensive reference dataset of detailed miRNA expression profiles from seven types of human peripheral blood cells (NK cells, B lymphocytes, cytotoxic T lymphocytes, T helper cells, monocytes, neutrophils and erythrocytes), serum, exosomes and whole blood. The peripheral blood cells from buffy coats were typed and sorted using FACS/MACS. The overall dataset was generated from 450 small RNA libraries using high-throughput sequencing. By employing a comprehensive bioinformatics and statistical analysis, we show that 3′ trimming modifications as well as composition of 3′ added non-templated nucleotides are distributed in a lineage-specific manner—the closer the hematopoietic progenitors are, the higher their similarities in sequence variation of the 3′ end. Furthermore, we define the blood cell-specific miRNA and isomiR expression patterns and identify novel cell type specific miRNA candidates. The study provides the most comprehensive contribution to date towards a complete miRNA catalogue of human peripheral blood, which can be used as a reference for future studies. The dataset has been deposited in GEO and also can be explored interactively following this link: http://134.245. 63.235/ikmb-tools/bloodmiRs.
Early understandings of the link between agents and order

The world around us presents two fundamentally different forms of patterns: those that appear random and those that appear ordered. As adults we appreciate that these two types of patterns tend to arise from very different sorts of causal processes. Typically, we expect that, whereas agents can increase the orderliness of a system, inanimate objects can cause only increased disorder. Thus, one major division in the world of causal entities is between those that are capable of “reversing local entropy” and those that are not. In the present studies we find that sensitivity to the unique link between agents and order emerges quite early in development. Results from three experiments suggest that by 12 mo of age infants associate agents with the creation of order and inanimate objects with the creation of disorder. Such expectations appear to be robust into children's preschool years and are hypothesized to result from a more general understanding that agents causally intervene on the world in fundamentally different ways from inanimate objects.
Protein‐Size Molecularly Imprinted Polymer Nanogels as Synthetic Antibodies, by Localized Polymerization with Multi‐initiators

A new approach is proposed for the synthesis of molecularly imprinted polymers (MIPs) (synthetic antibodies) as soluble nanogels with sizes close to the size of real antibodies. To imprint a molecular memory in particles consisting of only a few polymer chains, an initiator carrying multiple iniferter moieties is used. This allows for the simultaneous initiation of several polymer chains, and yields molecularly imprinted nanogels (17 nm, molecular weight (MW) = 97 kDa) with good affinity and selectivity for the target.
Correlation between liver histology and novel magnetic resonance imaging in adult patients with non‐alcoholic fatty liver disease – MRI accurately quantifies hepatic steatosis in NAFLD

Conventional magnetic resonance imaging (MRI) techniques that measure hepatic steatosis are limited by T1 bias, T2* decay and multi‐frequency signal‐interference effects of protons in fat. Newer MR techniques such as the proton density‐fat fraction (PDFF) that correct for these factors have not been specifically compared to liver biopsy in adult patients with non‐alcoholic fatty liver disease (NAFLD).
An Anchor for Tumor Cell Invasion

About half of patients with the blistering skin disorder recessive dystrophic epidermolysis bullosa caused by mutations in collagen VII are predisposed to developing epidermal cancers, whereas the remainder are not. In their Perspective, [Yuspa and Epstein][1] discuss new findings ([ Ortiz-Urda et al .][2]) that reveal the reason for this paradox. The ability of keratinocytes from these patients to become tumorigenic depends on whether the patients carry a collagen VII mutation that results in production of collagen VII containing the crucial NC1 domain. Keratinocytes from patients who carry a mutation that blocks production of collagen VII do not become tumorigenic. [1]: http://www.sciencemag. org/cgi/content/full/307/5716/1727 [2]: http://www.sciencemag. org/cgi/content/short/307/5716/1773
Self‐Assembled, Nanowire Network Electrodes for Depleted Bulk Heterojunction Solar Cells

Herein, a solution-processed, bottom-up-fabricated, nanowire network electrode is developed. This electrode features a ZnO template which is converted into locally connected, infiltratable, TiO2 nanowires. This new electrode is used to build a depleted bulk heterojunction solar cell employing hybrid-passivated colloidal quantum dots. The new electrode allows the application of a thicker, and thus more light-absorbing, colloidal quantum dot active layer, from which charge extraction of an efficiency comparable to that obtained from a thinner, planar device could be obtained.
Downstream class switching leads to IgE antibody production by B lymphocytes lacking IgM switch regions

Ig heavy chain (IgH) class-switch recombination (CSR) replaces the IgH Cμ constant region exons with one of several sets of downstream IgH constant region exons (e.g., Cγ, Cε, or Cα), which affects switching from IgM to another IgH class (e.g., IgG, IgE, or IgA). Activation-induced cytidine deaminase (AID) initiates CSR by promoting DNA double-strand breaks (DSBs) within switch (S) regions flanking the donor Cμ (Sμ) and a downstream acceptor CH (e.g., Sγ, Sε, Sα) that are then joined to complete CSR. DSBs generated in Sμ frequently are joined within Sμ to form internal switch region deletions (ISD). AID-induced ISD and mutations have been considered rare in downstream S regions, suggesting that AID targeting to these S regions requires its prior recruitment to Sμ. We have now assayed for CSR and ISD in B cells lacking Sμ (Sμ−/− B cells). In Sμ−/− B cells activated for CSR to IgG1 and IgE, CSR to IgG1 was greatly reduced; but, surprisingly, CSR to IgE occurred at nearly normal levels. Moreover, normal B cells had substantial Sγ1 ISD and increased mutations in and near Sγ1, and levels of both were greatly increased in Sμ−/− B cells. Finally, Sμ−/− B cells underwent downstream CSR between Sγ1 and Sε on alleles that lacked Sμ CSR to these sequences. Our findings show that AID targets downstream S regions independently of CSR with Sμ and implicate an alternative pathway for IgE class switching that involves generation and joining of DSBs within two different downstream S regions before Sμ joining.
A case of psoriatic arthritis without the appearance of psoriatic skin or nail lesions for 21 years

In some patients with psoriatic arthritis, arthritis may precede psoriatic skin lesions. In fact, psoriatic skin lesions may not develop for more than 10 years after the onset of arthritis. Making diagnostic and therapeutic decisions in such patients is therefore challenging. We describe a case with classic features of psoriatic arthritis without psoriatic skin or nail lesions for 21 years. We suggest that recognition of psoriatic arthritis sine psoriasis is important for selecting appropriate therapy to prevent joint damage.
Chemical composition of essential oil Tagetes minuta from Iran

Tagetes minuta L. belongs to Asteracea family it is an annual species native of South American, although it has become widespread throughout the world. This species is especially well adapted to disturbed habitats. Tagetes minuta oil found a good market in perfumery and flavour industry. Many studies on Tagetes minuta have reported that the composition of exteracted volatile components varied according to the harvesting location, the growth stage and the part of the plant. From these analyses, it can be deduced that Tagetes oils possess a varied composition according to intrinsic and or extrinsic factors, which reflect different physiological demands associated with growth, reproduction and defence. The purpose of this study was to characterize essential oil composition of Tagetes minuta cultivated in climatic condition of Iran. The experiment was carried out at experimental farm of Tarbiat Modaress University during the spering-summer growing season of 2003. The seed were sown during April. Aerial parts of the plant were collected at full bloom stage at October and dried at room temperature. Essential oil of dried-aerial parts of plant was isolated by hydro-distillation for 3 h using Clevenger type apparatus and was analysis by GC and GC/MS Towenty-two compounds were characterized with ? -terpineol (20.8%), (Z)- ? -ocimene (17.6%), dihydrotagetone (13.7%), (Z)-tagetone (8.3%), (E)-ocimenone (13.2%), (Z)-ocimenone (6%), cis-dihydro carrone (5%), l-terpineol (2.7%), limonene (2.6%), (E)-tagetone (1.9%) as major compounds.
Intra‐operative awareness in children and post‐traumatic stress disorder *

Adults who experience intra‐operative awareness can develop disturbing long‐lasting after‐effects, such as daytime anxiety, sleep disturbances, nightmares, flashbacks and, in the worst case, a post‐traumatic stress disorder (PTSD). It is unknown whether intra‐operative awareness has a similar psychological impact in children. We designed the present study in order to evaluate the incidence of psychological symptoms in children who had either confirmed or possible intra‐operative awareness. Attempts were made to locate 11 children who had been identified in a previous study, approximately 1 year following their experience. A PTSD questionnaire was administered to the children and their parents in order to detect any long‐term or short‐term psychological symptoms (the 1‐month postoperative data were evaluated retrospectively). Factors believed to be associated with PTSD, such as intra‐operative perceptions, the children’s temperament and cognitive strategies, and the parents’ coping strategies, were also analysed. Seven children were successfully located and interviewed and no short or long‐term psychological symptoms were identified. None of them offered negative appraisals of the traumatic event and none had displayed dysfunctional behaviour or cognitive strategies. Thus, none of them had developed a PTSD syndrome. In contrast with what has been reported in adults, these children claimed not to have experienced major pain, terror or helplessness during their surgery. Despite the small sample size, the results of the present study suggest that children suffer less psychological sequelae than adults following intra‐operative awareness. This may be due to the fact that the children reported less frightening intra‐operative sensations as compared with the adults, and had less understanding of the anaesthesia procedure, and this may have influenced their appraisal of their awareness and protected them from the full impact of this potentially traumatic experience.
Millimeter‐Size Single‐Crystal Graphene by Suppressing Evaporative Loss of Cu During Low Pressure Chemical Vapor Deposition

Millimeter-size single-crystal monolayer graphene is synthesized on polycrystalline Cu foil by a method that involves suppressing loss by evaporation of the Cu at high temperature under low pressure. This significantly diminishes the number of graphene domains, and large single crystal domains up to ∼2 mm in size are grown.
Management changes in the National Health Service : nursing and organisational theory in relation to the development of a new unit of health care

This thesis gives an account of research into management changes in the English NHS following the implementation of the Griffiths' Report (1983). The research had three aims: 1. To describe and consider the effects of new management philosophies plans and practices by conducting a case study of one particular unit of health care. 2. To study theories of nursing and health care organisation. 3. To assess the relationship, if any, between experience and theory, suggesting ways to bring theory and practice closer together. The academic perspective is multidisciplinary, drawing on literature from nursing, organisational 'theory and behaviour, health service management, social science, philosophy, history, economics and policy studies. The thesis commences with a discussion of research methodology, arguing the appropriateness of an interpretive stance. An account of the development of the NHS and nursing's place within it is followed by a detailed case study of one unit, which lasted nine months and involved more than a hundred interviews. Particular characteristics of the case study are:- Data analysis utilising grounded theory methodology Inclusion of members of the organisational context A system for participants to validate data pertaining to themselves. The style is naturalistic, qualitative and processual. Presentation of the results recognises the existence of multiple interpretations of organisational reality; a metaphor likens the development of the Unit to the weaving of a tapestry, where the backing is the structure of the unit, and the pattern the perceptions, values and aspirations of its staff, patients and context members. Emerging themes in the thesis are:- the complexity of the NHS professional philosophies and their relationship to management organising as a process growth of a distinctive unit culture. A deliberate choice is made to expose the conflicts and difficulties of naturalistic inquiry, by reflecting on research method throughout the thesis, which is written in the first person.
The Mohawk homeobox gene is a critical regulator of tendon differentiation

Mohawk (Mkx) is a member of the Three Amino acid Loop Extension superclass of atypical homeobox genes that is expressed in developing tendons. To investigate the in vivo functions of Mkx, we generated Mkx−/− mice. These mice had hypoplastic tendons throughout the body. Despite the reduction in tendon mass, the cell number in tail tendon fiber bundles was similar between wild-type and Mkx−/− mice. We also observed small collagen fibril diameters and a down-regulation of type I collagen in Mkx−/− tendons. These data indicate that Mkx plays a critical role in tendon differentiation by regulating type I collagen production in tendon cells.