Miracle-dz/UniFAR-FTUs huggingface dataset:
Ubiquitin-binding motif of human DNA polymerase η is required for correct localization

Acharya et al. (1) recently examined the role of different motifs in human DNA polymerase (pol)η. Their data suggested that mutations in the ubiquitin-binding (UBZ) motif of polη had no effect on its localization into replication foci. However, the first 4 authors of this Letter have independently found, in many experiments, that mutations D652A, C638A, and H654A in the UBZ motif all greatly reduced the accumulation of polη in replication foci (refs. ,2 and , …
Refined sgRNA efficacy prediction improves large- and small-scale CRISPR–Cas9 applications

Abstract Genome editing with the CRISPR–Cas9 system has enabled unprecedented efficacy for reverse genetics and gene correction approaches. While off-target effects have been successfully tackled, the effort to eliminate variability in sgRNA efficacies—which affect experimental sensitivity—is in its infancy. To address this issue, studies have analyzed the molecular features of highly active sgRNAs, but independent cross-validation is lacking. Utilizing fluorescent reporter knock-out assays with verification at selected endogenous loci, we experimentally quantified the target efficacies of 430 sgRNAs. Based on this dataset we tested the predictive value of five recently-established prediction algorithms. Our analysis revealed a moderate correlation (r = 0.04 to r = 0.20) between the predicted and measured activity of the sgRNAs, and modest concordance between the different algorithms. We uncovered a strong PAM-distal GC-content-dependent activity, which enabled the exclusion of inactive sgRNAs. By deriving nine additional predictive features we generated a linear model-based discrete system for the efficient selection (r = 0.4) of effective sgRNAs (CRISPRater). We proved our algorithms’ efficacy on small and large external datasets, and provide a versatile combined on- and off-target sgRNA scanning platform. Altogether, our study highlights current issues and efforts in sgRNA efficacy prediction, and provides an easily-applicable discrete system for selecting efficient sgRNAs.
The Different Designs of Molecule Logic Gates

From the bottom, it is demonstrated how all the known intramolecular single‐molecule logic gate architectures – semi‐classical circuits, quantum Hamiltonian circuits, and qubit circuits – are different versions of the quantum control of intramolecular processes. They only differ in the way the classical input data are encoded on the quantum molecular system and how the quantum‐to‐classical conversion proceeds to read the output.
The Role of Acid Sensing Ion Channels in Spinal Cord Injury

Abstract : Secondary neuronal damage occurs during the sub-acute phase of spinal cord injury (SCI) and is a major mechanism of permanent neurological dysfunction. The development of new hypotheses focusing on secondary damage is of paramount importance for devising new therapeutics to prevent the morbidity and mortality associated with spinal cord injury in humans. Recently, acidosis-evoked activation of the acid sensing ion channel 1a (ASIC1a) was determined to substantially contribute to secondary neuronal damage following cerebral ischemia. The purpose of this proposal is to determine how ASIC1a contributes to neuron death associated with SCI and whether administration of the ASIC1a inhibitor PcTx1 will significantly reduce neurological deficits following SCI. We will assess both immunohistochemical changes in the lesions as well as behavioral outcomes following injury. In the past year, we have determined that administration of the ASIC1a-inhibiting peptide PcTx1 1 hour after SCI results in an increased number of oligodendrocytes precursors in the injured spinal cord. The presence of the cells could afford better recovery from spinal cord contusion injury and indicates that further studies into the therapeutic potential of ASIC1 inhibitors to limit permanent damage following SCI are warranted. The completion of these aims will provide a foundation to promote further study on the role of acidosis in SCI and elucidate the therapeutic value of ASIC1a inhibition for SCI.
Vpu enhances HIV-1 virus release in the absence of Bst-2 cell surface down-modulation and intracellular depletion

HIV-1 Vpu enhances the release of virions from infected cells. Recent work identified Bst-2/CD317/tetherin as a host factor whose inhibitory activity on viral release is counteracted by Vpu. A current working model proposes that Bst-2 inhibits virus release by tethering viral particles to the cell surface. Here, we analyzed endogenous Bst-2 with respect to its effect on virus release from HeLa cells, T cells, and macrophages. We noted significant cell type-dependent variation in Bst-2 expression. Vpu caused a reduction in Bst-2 expression in transfected HeLa cells and long-term infected macrophages. However, Vpu expression did not result in cell surface down-modulation of Bst-2 or a reduction in intracellular Bst-2 expression in CEMx174 or H9 cells, yet virus replication in these cells was Vpu-responsive. Surprisingly, Bst-2 was undetectable in cell-free virions that were recovered from the surface of HeLa cells by physical shearing, suggesting that a tethering model may not explain all of the functional properties of Bst-2. Taken together we conclude that enhancement of virus release by Vpu does not, at least in CEMx174 and H9 cells, require cell surface down-modulation or intracellular depletion of Bst-2, nor does it entail exclusion of Bst-2 from viral particles.
Facile Synthesis of Free‐Standing Pd‐Based Nanomembranes with Enhanced Catalytic Performance for Methanol/Ethanol Oxidation

Macroscopic free-standing Pd and Pd/Pt bimetallic monolayer nanomembranes (Pd- and Pd/Pt-FNMs) derived from the spontaneous self-assembly of the as-produced Pd NPs and Pd/Pt bimetallic NPs at the water-air interface within 15 min are fabricated, respectively. The one-step method allows the growth of high-quality Pd-based FNMs with well-defined monolayer morphology, which exhibit significantly higher electrocatalytic activity for methanol/ethanol oxidation than commercial catalysts.
Progress in Piezotronics and Piezo‐Phototronics

The fundamental principle of piezotronics and piezo‐phototronics were introduced by Wang in 2007 and 2010, respectively. Due to the polarization of ions in a crystal that has non‐central symmetry in materials such as the wurtzite structured ZnO, GaN and InN, a piezoelectric potential (piezopotential) is created in the crystal by applying a stress. Owing to the simultaneous possession of piezoelectricity and semiconductor properties, the piezopotential created in the crystal has a strong effect on the carrier transport at the interface/junction. Piezotronics is about the devices fabricated using the piezopotential as a “gate” voltage to tune/control charge carrier transport at a contact or junction. The piezo‐phototronic effect is to use the piezopotential to control the carrier generation, transport, separation and/or recombination for improving the performance of optoelectronic devices, such as photon detector, solar cell and LED. This manuscript reviews the updated progress in the two new fields. A perspective is given about their potential applications in sensors, human‐silicon technology interfacing, MEMS, nanorobotics and energy sciences.
Mu transpososome activity-profiling yields hyperactive MuA variants for highly efficient genetic and genome engineering

Abstract The phage Mu DNA transposition system provides a versatile species non-specific tool for molecular biology, genetic engineering and genome modification applications. Mu transposition is catalyzed by MuA transposase, with DNA cleavage and integration reactions ultimately attaching the transposon DNA to target DNA. To improve the activity of the Mu DNA transposition machinery, we mutagenized MuA protein and screened for hyperactivity-causing substitutions using an in vivo assay. The individual activity-enhancing substitutions were mapped onto the MuA–DNA complex structure, containing a tetramer of MuA transposase, two Mu end segments and a target DNA. This analysis, combined with the varying effect of the mutations in different assays, implied that the mutations exert their effects in several ways, including optimizing protein–protein and protein–DNA contacts. Based on these insights, we engineered highly hyperactive versions of MuA, by combining several synergistically acting substitutions located in different subdomains of the protein. Purified hyperactive MuA variants are now ready for use as second-generation tools in a variety of Mu-based DNA transposition applications. These variants will also widen the scope of Mu-based gene transfer technologies toward medical applications such as human gene therapy. Moreover, the work provides a platform for further design of custom transposases.
Identification of serine/threonine kinase and nucleotide-binding site-leucine-rich repeat (NBS-LRR) genes in the fire blight resistance quantitative trait locus of apple cultivar 'Evereste'.

Fire blight is the most destructive bacterial disease affecting apple (Malus×domestica) worldwide. So far, no resistance gene against fire blight has been characterized in apple, despite several resistance regions having been identified. A highly efficacious resistance quantitative trait locus (QTL) was localized on linkage group 12 (LG12) of the ornamental cultivar 'Evereste'. A marker previously reported to be closely linked to this resistance was used to perform a chromosome landing. A bacterial artificial chromosome (BAC) clone of 189 kb carrying the fire blight resistance QTL was isolated and sequenced. New microsatellite markers were developed, and the genomic region containing the resistance locus was limited to 78 kb. A cluster of eight genes with homologies to already known resistance gene structures to bacterial diseases was identified and the corresponding gene transcription was verified. From this cluster, two genes were recognized in silico as the two most probable fire blight resistance genes showing homology with the Pto/Prf complex in tomato.
Reversible Tuning Luminescent Color and Emission Intensity: A Dipeptide‐Based Light‐Emitting Material

A smart luminescent material whose emission color and emission intensity can be separately modulated by external force is demonstrated. The rational manipulation of rich noncovalent interactions and fluorophore packing style promotes an in-depth understanding between supramolecular structure and photophysical property and offers an effective strategy to modulate the light-emitting property in a predicative way.
Nitrogen‐Doped Porous Carbon Nanofiber Webs as Anodes for Lithium Ion Batteries with a Superhigh Capacity and Rate Capability

Nitrogen-doped carbon nanofiber webs (CNFWs) with high surface areas are successfully prepared by carbonization-activation of polypyrrole nanofiber webs with KOH. The as-obtained CNFWs exhibit a superhigh reversible capacity of 943 mAh g(-1) at a current density of 2 A g(-1) even after 600 cycles, which is ascribed to the novel porous nanostructure and high-level nitrogen doping.
Etkinlik Teorisine Göre Zenginleştirilmiş Birleştirilmiş Sınıflarda Öğretim Uygulamalarının Adayların Özyeterlik Algılarına Etkisi

This study aimed to determine the effect of practices provided according to the activity theory through course of Teaching in Multigrade Classes on pre-service student teachers’ levels of self-efficacy regarding teaching in multigrade classes comparing with another course practices. The data in this quasi-experimental study were collected through pre-test, group procedures, post-test research design. T-tests were used for the relational measures, and (r) statistic was used for effect sizes. The results of the study showed that the practices included in the two different programs contributed to increasing self-efficacy levels in student teachers to teach in multigrade classes at a significant level, and that the instructional curriculum which incorporates activities based on activity theory was found to have a higher effect on students’ self-efficacy levels compared to the other instructional curriculum.
COUP-TFII acts downstream of Wnt/β-catenin signal to silence PPARγ gene expression and repress adipogenesis

Wnt signaling through β-catenin and TCF maintains preadipocytes in an un-differentiated proliferative state; however, the molecular pathway has not been completely defined. By integrating gene expression microarray, chromatin immunoprecipitation-chip, and cell-based experimental approaches, we show that Wnt/β-catenin signaling activates the expression of COUP-TFII which recruits the SMRT corepressor complex to the first introns located downstream from the first exons of both PPARγ1 and γ2 mRNAs. This maintains the local chromatin in a hypoacetylated state and represses PPARγ gene expression to inhibit adipogenesis. Our experiments define the COUP-TFII/SMRT complex as a previously unappreciated component of the linear pathway that directly links Wnt/β-catenin signaling to repression of PPARγ gene expression and the inhibition of adipogenesis.
Mitochondrial phosphoglycerate mutase 5 uses alternate catalytic activity as a protein serine/threonine phosphatase to activate ASK1

Phosphoglycerate mutase (PGAM) is an enzyme of intermediary metabolism that converts 3-phosphoglycerate to 2-phosphoglycerate in glycolysis. Here, we discovered PGAM5 that is anchored in the mitochondrial membrane lacks PGAM activity and instead associates with the MAP kinase kinase kinase ASK1 and acts as a specific protein Ser/Thr phosphatase that activates ASK1 by dephosphorylation of inhibitory sites. Mutation of an active site His-105 in PGAM5 abolished phosphatase activity with ASK1 and phospho-Thr peptides as substrates. The Drosophila and Caenorhabditis elegans orthologs of PGAM5 also exhibit specific Ser/Thr phosphatase activity and activate the corresponding Drosophila and C. elegans ASK1 kinases. PGAM5 is unrelated to the other known Ser/Thr phosphatases of the PPP, MPP, and FCP families, and our results suggest that this member of the PGAM family has crossed over from small molecules to protein substrates and been adapted to serve as a specialized activator of ASK1.
Zinc Hydroxyapatite Catalyst for Decomposition of 2‐Propanol

the of nano-scale hydroxyapatite The general of hexagonal (P6 ) HAp F 4 ) 2 where one-dimensional channels are con-structed from columns of framework (F) metaprisms (Ca F O 6 ) that are corner-connected to PO 4 tetrahedra, with the tunnels (T) having an ideal stoichiometry Ca T (OH) 2 . [ 2 ] In common with other small transition metal cations, the incorporation of zinc into HAp inhibits crystal growth, and promotes tricalcium phosphate (TCP) formation at higher calcination temperatures (usually > 700 ° C). [ 3 Functionality can be manipulated through a metastable amorphous calcium phosphate (ACP) phase that co-exists during the incorporation of Zn 2 + , and promotes surface adsorption and reactivity. The solid solubility limit of Zn 2 + , which will displace Ca 2 + (Ca 2 + → Zn 2 + ) and can potentially par-tition to either the framework or tunnel, remains low to satisfy the bond valence sum restrictions. Because Zn 2
Intimate bacterial–fungal interaction triggers biosynthesis of archetypal polyketides in Aspergillus nidulans

Fungi produce numerous low molecular weight molecules endowed with a multitude of biological activities. However, mining the full-genome sequences of fungi indicates that their potential to produce secondary metabolites is greatly underestimated. Because most of the biosynthesis gene clusters are silent under laboratory conditions, one of the major challenges is to understand the physiological conditions under which these genes are activated. Thus, we cocultivated the important model fungus Aspergillus nidulans with a collection of 58 soil-dwelling actinomycetes. By microarray analyses of both Aspergillus secondary metabolism and full-genome arrays and Northern blot and quantitative RT-PCR analyses, we demonstrate at the molecular level that a distinct fungal-bacterial interaction leads to the specific activation of fungal secondary metabolism genes. Most surprisingly, dialysis experiments and electron microscopy indicated that an intimate physical interaction of the bacterial and fungal mycelia is required to elicit the specific response. Gene knockout experiments provided evidence that one induced gene cluster codes for the long-sought after polyketide synthase (PKS) required for the biosynthesis of the archetypal polyketide orsellinic acid, the typical lichen metabolite lecanoric acid, and the cathepsin K inhibitors F-9775A and F-9775B. A phylogenetic analysis demonstrates that orthologs of this PKS are widespread in nature in all major fungal groups, including mycobionts of lichens. These results provide evidence of specific interaction among microorganisms belonging to different domains and support the hypothesis that not only diffusible signals but intimate physical interactions contribute to the communication among microorganisms and induction of otherwise silent biosynthesis genes.
Large Magnetoresistance in Few Layer Graphene Stacks with Current Perpendicular to Plane Geometry

A large magnetoresistance (MR) effect of few-layers graphene between two non-magnetic metal electrodes with current perpendicular to graphene plane is studied. A non-saturation and anisotropic MR with the value over 60% at 14 T is observed in a two-layer graphene stack at room temperature. The resistance of the device is only tens of ohms, having the advantage of low power consumption for magnetic device applications.
Ordered Nanopillar Structured Electrodes for Depleted Bulk Heterojunction Colloidal Quantum Dot Solar Cells

A bulk heterojunction of ordered titania nanopillars and PbS colloidal quantum dots is developed. By using a pre-patterned template, an ordered titania nanopillar matrix with nearest neighbours 275 nm apart and height of 300 nm is fabricated and subsequently filled in with PbS colloidal quantum dots to form an ordered depleted bulk heterojunction exhibiting power conversion efficiency of 5.6%.
Cyanobacterial daily life with Kai-based circadian and diurnal genome-wide transcriptional control in Synechococcus elongatus

In the unicellular cyanobacterium Synechococcus elongatus PCC 7942, essentially all promoter activities are under the control of the circadian clock under continuous light (LL) conditions. Here, we used high-density oligonucleotide arrays to explore comprehensive profiles of genome-wide Synechococcus gene expression in wild-type, kaiABC-null, and kaiC-overexpressor strains under LL and continuous dark (DD) conditions. In the wild-type strains, >30% of transcripts oscillated significantly in a circadian fashion, peaking at subjective dawn and dusk. Such circadian control was severely attenuated in kaiABC-null strains. Although it has been proposed that KaiC globally represses gene expression, our analysis revealed that dawn-expressed genes were up-regulated by kaiC-overexpression so that the clock was arrested at subjective dawn. Transfer of cells to DD conditions from LL immediately suppressed expression of most of the genes, while the clock kept even time in the absence of transcriptional feedback. Thus, the Synechococcus genome seems to be primarily regulated by light/dark cycles and is dramatically modified by the protein-based circadian oscillator.
Tailoring of Mesenchymal Stem Cells Behavior on Plasma‐Modified Polytetrafluoroethylene

By altering the surface properties of polytetrafluoroethylene (PTFE) substrates using a special PIII technique, mesenchymal stem cells (MSCs) proliferation and osteogenesis can be promoted in culture without osteogenic supplements. The structures are created intrinsically in the PTFE for no risk of materials delamination. Large-scale features and locally different functions can also be readily produced on the same substrate by this technique.
Development and Application of Multiple‐Probe Scanning Probe Microscopes

In the research of advanced materials based on nanoscience and nanotechnology, it is often desirable to measure nanoscale local electrical conductivity at a designated position of a given sample. For this purpose, multiple‐probe scanning probe microscopes (MP‐SPMs), in which two, three or four scanning tunneling microscope (STM) or atomic force microscope (AFM) probes are operated independently, have been developed. Each probe in an MP‐SPM is used not only for observing high‐resolution STM or AFM images but also for forming an electrical contact enabling nanoscale local electrical conductivity measurement. The world's first double‐probe STM (DP‐STM) developed by the authors, which was subsequently modified to a triple‐probe STM (TP‐STM), has been used to measure the conductivities of one‐dimensional metal nanowires and carbon nanotubes and also two‐dimensional molecular films. A quadruple‐probe STM (QP‐STM) has also been developed and used to measure the conductivity of two‐dimensional molecular films without the ambiguity of contact resistance between the probe and sample. Moreover, a quadruple‐probe AFM (QP‐AFM) with four conductive tuning‐fork‐type self‐detection force sensing probes has been developed to measure the conductivity of a nanostructure on an insulating substrate. A general‐purpose computer software to control four probes at the same time has also been developed and used in the operation of the QP‐AFM. These developments and applications of MP‐SPMs are reviewed in this paper.
Socio-demographics and Clinical Characteristics of Patients with Conversion Disorder

The study explored the socio-demographic and clinical characteristics of patients diagnosed with conversion disorder, as defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR, American Psychiatric Association, 2000). 47 diagnosed patients visiting Out-patient Clinic of Institute of Clinical Psychology, University of Karachi, Pakistan, during 2005-2006 were interviewed through a semi-structured Interview Form for Psychological Assessment designed by the Institute of Clinical Psychology, University of Karachi. Results indicate that mean age of the sample was 26.44 years; 76.59% being women; 59.57% were unmarried; 63.83% belonged to middle socioeconomic status. Majority of the patients had less than or up till 10 years of schooling (61.70%); 51.06% had middle birth order; and 53.19% were living in nuclear family structure. Also, 46.8% experienced mixed symptoms whereas 23.4% experienced motor symptoms. The most common stressor identified was problem with primary support group (36.2%). Mean score on Global Ass'essment of Functioning was 56.
DNAproDB: an interactive tool for structural analysis of DNA–protein complexes

Abstract Many biological processes are mediated by complex interactions between DNA and proteins. Transcription factors, various polymerases, nucleases and histones recognize and bind DNA with different levels of binding specificity. To understand the physical mechanisms that allow proteins to recognize DNA and achieve their biological functions, it is important to analyze structures of DNA–protein complexes in detail. DNAproDB is a web-based interactive tool designed to help researchers study these complexes. DNAproDB provides an automated structure-processing pipeline that extracts structural features from DNA–protein complexes. The extracted features are organized in structured data files, which are easily parsed with any programming language or viewed in a browser. We processed a large number of DNA–protein complexes retrieved from the Protein Data Bank and created the DNAproDB database to store this data. Users can search the database by combining features of the DNA, protein or DNA–protein interactions at the interface. Additionally, users can upload their own structures for processing privately and securely. DNAproDB provides several interactive and customizable tools for creating visualizations of the DNA–protein interface at different levels of abstraction that can be exported as high quality figures. All functionality is documented and freely accessible at http://dnaprodb.usc. edu.