Miracle-dz/UniFAR-FTUs huggingface dataset:
Photo‐Click Living Strategy for Controlled, Reversible Exchange of Biochemical Ligands

A novel addition-fragmentation-chain transfer capable allyl sulfide functionalized PEG hydrogel is reported to allow controlled, reversible exchange of biochemical ligands. The exchange of biochemical ligands is achieved without permanent consumption of reactive functionalities. Demonstrated is the ability to exchange biochemical ligands multiple times using cytocompatible 720 nm two-photon light.
Light‐Directed Electrophoretic Deposition: A New Additive Manufacturing Technique for Arbitrarily Patterned 3D Composites

Dr. A. J. Pascall, Dr. F. Qian, Dr. M. A. Worsley, Dr. J. D. Kuntz Lawrence Livermore National Laboratory Livermore , CA 94550 , USA E-mail: pascall1@llnl.gov G. Wang, Prof. Y. Li Department of Chemistry and Biochemistry University of California Santa Cruz , CA 95064 , USA
Mitochondrial DNA D-loop sequence variation in maternal lineages of Iranian native horses.

To understand the origin and genetic diversity of Iranian native horses, mitochondrial DNA (mtDNA) D-loop sequences were generated for 95 horses from five breeds sampled in eight geographical locations in Iran. Sequence analysis of a 247-bp segment revealed a total of 27 haplotypes with 38 polymorphic sites. Twelve of 19 mtDNA haplogroups were identified in the samples. The most common haplotypes were found within haplogroup X2. Within-population haplotype and nucleotide diversities of the five breeds ranged from 0.838 ± 0.056 to 0.974 ± 0.022 and 0.011 ± 0.002 to 0.021 ± 0.001 respectively, indicating a relatively high genetic diversity in Iranian horses. The identification of several ancient sequences common between the breeds suggests that the lineage of the majority of Iranian horse breeds is old and obviously originated from a vast number of mares. We found in all native Iranian horse breeds lineages of the haplogroups D and K, which is concordant with the previous findings of Asian origins of these haplogroups. The presence of haplotypes E and K in our study also is consistent with a geographical west-east direction of increasing frequency of these haplotypes and a genetic fusion in Iranian horse breeds.
Cysteine scanning and modification reveal major differences between BK channels and Kv channels in the inner pore region

BK channels are regulated by two distinct physiological signals, transmembrane potential and intracellular Ca2+, each acting through independent modular sensor domains. However, despite a presumably central role in the coupling of sensor activation to channel gating, the pore-lining S6 transmembrane segment has not been systematically studied. Here, cysteine substitution and modification studies of the BK S6 point to substantial differences between BK and Kv channels in the structure and function of the S6-lined inner pore. Gating shifts caused by introduction of cysteines define a pattern and direction of free energy changes in BK S6 distinct from Shaker. Modification of BK S6 residues identifies pore-facing residues that occur at different linear positions along aligned BK and Kv S6 segments. Periodicity analysis suggests that one factor contributing to these differences may be a disruption of the BK S6 α-helix from the unique diglycine motif at the position of the Kv hinge glycine. State-dependent MTS accessibility reveals that, even in closed states, modification can occur. Furthermore, the inner pore of BK channels is much larger than that of K+ channels with solved crystal structures. The results suggest caution in the use of Kv channel structures as templates for BK homology models, at least in the pore-gate domain.
The catalytic domain of all eukaryotic cut-and-paste transposase superfamilies

Cut-and-paste DNA transposable elements are major components of eukaryotic genomes and are grouped into superfamilies (e.g., hAT, P) based on sequence similarity of the element-encoded transposase. The transposases from several superfamilies possess a protein domain containing an acidic amino acid triad (DDE or DDD) that catalyzes the “cut and paste” transposition reaction. However, it was unclear whether this domain was shared by the transposases from all superfamilies. Through multiple-alignment of transposase sequences from a diverse collection of previously identified and recently annotated elements from a wide range of organisms, we identified the putative DDE/D triad for all superfamilies. Furthermore, we identified additional highly conserved amino acid residues or motifs within the DDE/D domain that together form a “signature string” that is specific to each superfamily. These conserved residues or motifs were exploited as phylogenetic characters to infer evolutionary relationships among all superfamilies. The phylogenetic analysis revealed three major groups that were not previously discerned and led us to revise the classification of several currently recognized superfamilies. Taking the data together, this study suggests that all eukaryotic cut-and-paste transposable element superfamilies have a common evolutionary origin and establishes a phylogenetic framework for all future cut-and-paste transposase comparisons.
Highly Stretchable Resistive Pressure Sensors Using a Conductive Elastomeric Composite on a Micropyramid Array

A stretchable resistive pressure sensor is achieved by coating a compressible substrate with a highly stretchable electrode. The substrate contains an array of microscale pyramidal features, and the electrode comprises a polymer composite. When the pressure-induced geometrical change experienced by the electrode is maximized at 40% elongation, a sensitivity of 10.3 kPa(-1) is achieved.
Bromide as marker for drug adherence in hypertensive patients.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Insufficient drug adherence is an important reason for inadequate blood pressure control. Currently, methods that measure drug adherence objectively are lacking. Objective methods are needed to help improve blood pressure control and outcome in hypertensive patients. WHAT THIS STUDY ADDS Potassium bromide added to antihypertensive drugs can be used to monitor drug adherence in individual patients. However, although this method is objective, it is rather time-, cost- and work-consuming. AIMS Adherence to antihypertensive medication is essential for adequate long-term control of blood pressure (BP). This study investigated different methods of measuring adherence in hypertensive patients. METHODS Patients were included if BP was insufficiently controlled on monotherapy. After a placebo period patients were treated with trandolapril 2 mg/verapamil SR 180 mg (TV). BP was determined using a mercury sphygmomanometer and ambulatory BP monitoring. Adherence was measured by capsule counting, electronic registration of pill-box openings and by measuring serum bromide concentrations. Potassium bromide was added to each TV capsule. RESULTS Thirty patients participated in the study. Treatment with TV significantly lowered office BP and ambulatory BP. Results for electronic monitoring and adherence based on bromide measurements were comparable. Adherence was slightly higher when assessed by capsule counting. CONCLUSIONS Measuring serum bromide concentrations may be suitable for assessment of adherence to drug therapy giving comparable results to electronic monitoring. Using capsule counting, electronic monitoring and measurement of bromide concentrations, nonadherent patients were identified.
Prevalence of Neoplasia, Caries and Gingivitis in Pediatric Cancer Patients in the City of Belém, PA, Brazil

Objetivo: Avaliar clinicamente a prevalencia de carie e gengivite em 62 criancas de 3 a 12 anos de idade, de ambos os generos sendo que 32 eram portadoras de neoplasias e 30 eram saudaveis, fazendo parte do grupo controle. Metodos: Os pacientes foram avaliados utilizando-se os indices CPO-d, ceo-d, Indice de Placa (IP) e Indice gengival (IG), sendo avaliados em dois momentos, antes e seis meses apos o inicio do estudo. Na analise estatistica, para verificar a interdependencia entre as variaveis, utilizaram-se os testes Exato de Fisher e Wilcoxon (p<0,05). Resultados: Verificou-se que a neoplasia mais frequente foi a leucemia e a terapia mais utilizada foi a quimioterapia. Com relacao a carie dental, pode-se observar ao examinarmos os pacientes inicialmente e apos um periodo de seis meses, que os indices de carie (CPO-D e ceo-d) aumentaram em ambos os grupos, no entanto, sendo estatisticamente significante entre os dois momentos do exame, no grupo de pacientes oncologicos. Ja com relacao aos indices de placa e gengival (IP e IG), nao houve diferencas estatisticamente significante entre os grupos analisados e, tambem, entre os dois momentos de avaliacao. Conclusao: Desse modo, ressalta-se a importância do odontopediatra na equipe de atendimento destes pacientes, para detectar, orientar e prevenir as principais manifestacoes bucais decorrentes da doenca e do tratamento.
Contribution of a mutational bias in hepatitis C virus replication to the genetic barrier in the development of drug resistance

The development of resistance to direct-acting antivirals (DAAs) targeting the hepatitis C virus (HCV) can compromise therapy. However, mechanisms that determine prevalence and frequency of resistance-conferring mutations remain elusive. Here, we studied the fidelity of the HCV RNA-dependent RNA polymerase NS5B in an attempt to link the efficiency of mismatch formation with genotypic changes observed in vivo. Enzyme kinetic measurements revealed unexpectedly high error rates (approximately 10-3 per site) for G∶U/U∶G mismatches. The strong preference for G∶U/U∶G mismatches over all other mistakes correlates with a mutational bias in favor of transitions over transversions. Deep sequencing of HCV RNA samples isolated from 20 treatment-naïve patients revealed an approximately 75-fold difference in frequencies of the two classes of mutations. A stochastic model based on these results suggests that the bias toward transitions can also affect the selection of resistance-conferring mutations. Collectively, the data provide strong evidence to suggest that the nature of the nucleotide change can contribute to the genetic barrier in the development of resistance to DAAs.
Gastro-intestinal haemorrhage risks of selective serotonin receptor antagonist therapy: a new look.

AIMS (i) To determine the effects of selective serotonin reuptake inhibitors (SSRI) and other classes of antidepressants on upper gastro-intestinal (GI) haemorrhage and (ii) to assess the drug-drug interaction effects of antidepressants and warfarin or clopidogrel on the risk of GI haemorrhage. METHODS This was a population-based case control study in the General Practice Research Database (GPRD). Cases with a first episode of upper GI haemorrhage between 2000 and 2005 were matched with up to 10 controls. Exposure to the study drugs was defined by a prescription issued in the 90 days before the index date. Rate ratios were estimated using conditional logistic regression. RESULTS Four thousand and twenty-eight cases of GI haemorrhage and 40 171 controls were identified. The excess risk of GI haemorrhage with SSRI use was small (Rate Ratio [RR]: 1.3; 95% confidence interval [CI]: 1.1, 1.6) and null with exposure to tricyclic antidepressants (TCAs) (RR 1.0; 95% CI: 0.8, 1.3). The risk of GI haemorrhage was highest with venlafaxine use (RR: 1.9; 95% CI: 1.3, 2.6). There was no drug-drug interaction between warfarin anticoagulation and antidepressant use. CONCLUSIONS This study supports a small increased risk of upper GI haemorrhage with the use of SSRI antidepressants compared with the older TCA drugs, but to a lesser extent than previously reported due to confounding by alcohol use. The small elevation in risk of GI haemorrhage with SSRI and venlafaxine should be weighed against the therapeutic benefit of their use.
Caring for Patients with Diabetes in Safety Net Hospitals and Health Systems

Safety net hospital systems provide health care to a high volume of underserved patients, including uninsured and low-income patients, racial/ethnic minorities, and those with chronic conditions. To assess the effects of programs designed to improve care for the undeserved, the National Public Health and Hospital Institute interviewed administrators about available programs and services and collected information on patient demographics, health care utilization, and clinical outcomes related to diabetes management. Services range from availability of special diabetes clinics to American Diabetes Association–certified classes. Compared with other health care providers, safety net hospital systems provide comparably high quality of care to patients with diabetes, despite serving higher volumes of underserved patients. However, even with programs and services designed to improve access to care for the underserved, disparities in quality of care and patient outcomes persist as a result of demographic risk factors, most notably, lack of insurance.
TGIF1 homeodomain interacts with Smad MH1 domain and represses TGF-β signaling

Abstract TGIF1 is a multifunctional protein that represses TGF-β-activated transcription by interacting with Smad2-Smad4 complexes. We found that the complex structure of TGIF1–HD bound to the TGACA motif revealed a combined binding mode that involves the HD core and the major groove, on the one hand, and the amino-terminal (N-term) arm and the minor groove of the DNA, on the other. We also show that TGIF1–HD interacts with the MH1 domain of Smad proteins, thereby indicating that TGIF1–HD is also a protein-binding domain. Moreover, the formation of the HD-MH1 complex partially hinders the DNA-binding site of the complex, preventing the efficient interaction of TGIF1–HD with DNA. We propose that the binding of the TGIF1 C-term to the Smad2-MH2 domain brings both the HD and MH1 domain into close proximity. This local proximity facilitates the interaction of these DNA-binding domains, thus strengthening the formation of the protein complex versus DNA binding. Once the protein complex has been formed, the TGIF1-Smad system would be released from promoters/enhancers, thereby illustrating one of the mechanisms used by TGIF1 to exert its function as an active repressor of Smad-induced TGF-β signaling.
Glycogen synthase kinase 3β transfers cytoprotective signaling through connexin 43 onto mitochondrial ATP-sensitive K+ channels

Despite compelling evidence supporting key roles for glycogen synthase kinase 3β (GSK3β), mitochondrial adenosine triphosphate-sensitive K+ (mitoKATP) channels, and mitochondrial connexin 43 (Cx43) in cytoprotection, it is not clear how these signaling modules are linked mechanistically. By patch-clamping the inner membrane of murine cardiac mitochondria, we found that inhibition of GSK3β activated mitoKATP. PKC activation and protein phosphatase 2a inhibition increased the open probability of mitoKATP channels through GSK3β, and this GSK3β signal was mediated via mitochondrial Cx43. Moreover, (i) PKC-induced phosphorylation of mitochondrial Cx43 was reduced in GSK3β-S9A mice; (ii) Cx43 and GSK3β proteins associated in mitochondria; and (iii) SB216763-mediated reduction of infarct size was abolished in Cx43 KO mice in vivo, consistent with the notion that GSK3β inhibition results in mitoKATP opening via mitochondrial Cx43. We therefore directly targeted mitochondrial Cx43 by the Cx43 C-terminal binding peptide RRNYRRNY for cardioprotection, circumventing further upstream pathways. RRNYRRNY activated mitoKATP channels via Cx43. We directly recorded mitochondrial Cx43 channels that were activated by RRNYRRNY and blocked by the Cx43 mimetic peptide 43GAP27. RRNYRRNY rendered isolated cardiomyocytes in vitro and the heart in vivo resistant to ischemia/reperfusion injury, indicating that mitochondrial Cx43- and/or mitoKATP-mediated reduction of infarct size was not undermined by RRNYRRNY-related opening of sarcolemmal Cx43 channels. Our results demonstrate that GSK3β transfers cytoprotective signaling through mitochondrial Cx43 onto mitoKATP channels and that Cx43 functions as a channel in mitochondria, being an attractive target for drug treatment against cardiomyocyte injury.
High‐Performance Quantum‐Dot Solids via Elemental Sulfur Synthesis

An elemental-sulfur-based synthesis is reported, which, combined with processing to improve the size dispersion and passivation, results in a low-cost high-quality platform for small-bandgap PbS-CQD-based devices. Size-selective precipitation and cadmium chloride passivation are used to improve the power conversion efficiency of 1 eV bandgap CQD photovoltaic devices dramatically, which leads to record power conversion efficiency for a 1 eV PbS CQD solar cell of 5.4%.
Deactivation of the Arabidopsis BRASSINOSTEROID INSENSITIVE 1 (BRI1) receptor kinase by autophosphorylation within the glycine-rich loop

The activity of the dual-specificity receptor kinase, brassinosteroid insensitive 1 (BRI1), reflects the balance between phosphorylation-dependent activation and several potential mechanisms for deactivation of the receptor. In the present report, we elucidate a unique mechanism for deactivation that involves autophosphorylation of serine-891 in the ATP-binding domain. Serine-891 was identified previously as a potential site of autophosphorylation by mass spectrometry, and sequence-specific antibodies and mutagenesis studies now unambiguously establish phosphorylation of this residue. In vivo, phosphorylation of serine-891 increased slowly with time following application of brassinolide (BL) to Arabidopsis seedlings, whereas phosphorylation of threonine residues increased rapidly and then remained constant. Transgenic plants expressing the BRI1(S891A)–Flag-directed mutant have increased hypocotyl and petiole lengths, relative to wild-type BRI1–Flag (both in the bri1-5 background), and accumulate higher levels of the unphosphorylated form of the BES1 transcription factor in response to exogenous BL. In contrast, plants expressing the phosphomimetic S891D-directed mutant are severely dwarfed and do not accumulate unphosphorylated BES1 in response to BL. Collectively, these results suggest that autophosphorylation of serine-891 is one of the deactivation mechanisms that inhibit BRI1 activity and BR signaling in vivo. Many arginine-aspartate (RD)-type leucine-rich repeat receptor-like kinases have a phosphorylatable residue within the ATP-binding domain, suggesting that this mechanism may play a broad role in receptor kinase deactivation.
Heat shock protein 90 (HSP90) contributes to cytosolic translocation of extracellular antigen for cross-presentation by dendritic cells

In antigen (Ag) cross-presentation, dendritic cells (DCs) take up extracellular Ag and translocate them from the endosome to the cytosol for proteasomal degradation. The processed peptides can enter the conventional MHC I pathway. The molecules responsible for the translocation of Ag across the endosomal membrane into the cytosol are unknown. Here we demonstrate that heat shock protein 90 (HSP90) is critical for this step. Cross-presentation and -priming were decreased in both HSP90α-null DCs and mice. CD8α+ DC apoptosis mediated by translocation of exogenous cytochrome c to the cytosol was also eliminated in HSP90α-null mice. Ag translocation into the cytosol was diminished in HSP90α-null DCs and in DCs treated with an HSP90 inhibitor. Internalized Ag was associated with HSP90 and translocated to the cytosol, a process abrogated by the HSP90 inhibitor. Ag within purified phagosomes was released in an HSP90-dependent manner. These results demonstrate the important role of HSP90 in cross-presentation by pulling endosomal Ag out into the cytosol.
Reduced Graphene Oxides: Light‐Weight and High‐Efficiency Electromagnetic Interference Shielding at Elevated Temperatures

Chemical graphitized r-GOs, as the thinnest and lightest material in the carbon family, exhibit high-efficiency electromagnetic interference (EMI) shielding at elevated temperature, attributed to the cooperation of dipole polarization and hopping conductivity. The r-GO composites show different temperature-dependent imaginary permittivities and EMI shielding performances with changing mass ratio.
3D Mapping of Crystallographic Phase Distribution using Energy‐Selective Neutron Tomography

Nondestructive 3D mapping of crystallographic phases is introduced providing distribution of phase fractions within the bulk (centimeter range) of samples with micrometer-scale resolution. The novel neutron tomography based technique overcomes critical limitations of existing techniques and offers a wide range of potential applications. It is demonstrated for steel samples exhibiting phase transformation after being subjected to tensile and torsional deformation.
OCT4 establishes and maintains nucleosome-depleted regions that provide additional layers of epigenetic regulation of its target genes

Recent epigenome-wide mapping studies describe nucleosome-depleted regions (NDRs) at transcription start sites and enhancers. However, these static maps do not address causality or the roles of NDRs in gene control, and their relationship to transcription factors and DNA methylation is not well understood. Using a high-resolution single-molecule mapping approach to simultaneously investigate endogenous DNA methylation and nucleosome occupancies on individual DNA molecules, we show that the unmethylated OCT4 distal enhancer has an NDR, whereas NANOG has a clear NDR at its proximal promoter. These NDRs are maintained by binding of OCT4 and are required for OCT4 and NANOG expression. Differentiation causes a rapid loss of both NDRs accompanied by nucleosome occupancy, which precedes de novo DNA methylation. NDRs can be restored by forced expression of OCT4 in somatic cells but only when there is no cytosine methylation. These data show the central role of the NDRs, established by OCT4, in ensuring the autoregulatory loop of pluripotency and, furthermore, that de novo methylation follows the loss of NDRs and stabilizes the suppressed state.
Theoretical Comparison, Equivalent Transformation, and Conjunction Operations of Electromagnetic Induction Generator and Triboelectric Nanogenerator for Harvesting Mechanical Energy

Triboelectric nanogenerator (TENG) is a newly invented technology that is effective using conventional organic materials with functionalized surfaces for converting mechanical energy into electricity, which is light weight, cost‐effective and easy scalable. Here, we present the first systematic analysis and comparison of EMIG and TENG from their working mechanisms, governing equations and output characteristics, aiming at establishing complementary applications of the two technologies for harvesting various mechanical energies. The equivalent transformation and conjunction operations of the two power sources for the external circuit are also explored, which provide appropriate evidences that the TENG can be considered as a current source with a large internal resistance, while the EMIG is equivalent to a voltage source with a small internal resistance. The theoretical comparison and experimental validations presented in this paper establish the basis of using the TENG as a new energy technology that could be parallel or possibly equivalently important as the EMIG for general power application at large‐scale. It opens a field of organic nanogenerator for chemists and materials scientists who can be first time using conventional organic materials for converting mechanical energy into electricity at a high efficiency.