Fabrication of Multifunctional Electronic Textiles Using Oxidative Restructuring of Copper into a Cu-Based Metal-Organic Framework.

This paper describes a novel synthetic approach for the conversion of zero-valent copper metal into a conductive two-dimensional layered metal-organic framework (MOF) based on 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP) to form Cu3(HHTP)2. This process enables patterning of Cu3(HHTP)2 onto a variety of flexible and porous woven (cotton, silk, nylon, nylon/cotton blend, and polyester) and non-woven (weighing paper and filter paper) substrates with microscale spatial resolution. The method produces conductive textiles with sheet resistances of 0.1-10.1 MΩ/cm2, depending on the substrate, and uniform conformal coatings of MOFs on textile swatches with strong interfacial contact capable of withstanding chemical and physical stresses, such as detergent washes and abrasion. These conductive textiles enable simultaneous detection and detoxification of nitric oxide and hydrogen sulfide, achieving part per million limits of detection in dry and humid conditions. The Cu3(HHTP)2 MOF also demonstrated filtration capabilities of H2S, with uptake capacity up to 4.6 mol/kgMOF. X-ray photoelectron spectroscopy and diffuse reflectance infrared spectroscopy show that the detection of NO and H2S with Cu3(HHTP)2 is accompanied by the transformation of these species to less toxic forms, such as nitrite and/or nitrate and copper sulfide and Sx species, respectively. These results pave the way for using conductive MOFs to construct extremely robust electronic textiles with multifunctional performance characteristics.

Au/TiO2-Catalyzed Benzyl Alcohol Oxidation on Morphologically Precise Anatase Nanoparticles.

Au nanoparticles (NP) on TiO2 have been shown to be effective catalysts for selective oxidation reactions by using molecular oxygen. In this work, we have studied the influence of support morphology on the catalytic activity of Au/TiO2 catalysts. Two TiO2 anatase supports, a nanoplatelet-shaped material with predominantly the {001} facet exposed and a truncated bipyramidal-shaped nanoparticle with predominantly the {101} facet exposed, were prepared by using a nonaqueous solvothermal method and characterized by using DRIFTS, XPS, and TEM. Au nanoparticles were deposited on the supports by using the deposition-precipitation method, and particle sizes were determined by using STEM. Au nanoparticles were smaller on the support with the majority of the {101} facet exposed. The resulting materials were used to catalyze the aerobic oxidation of benzyl alcohol and trifluoromethylbenzyl alcohol. Support morphology impacts the catalytic activity of Au/TiO2; reaction rates for reactions catalyzed by the predominantly {101} material were higher. Much of the increased reactivity can be explained by the presence of smaller Au particles on the predominantly {101} material, providing more Au/TiO2 interface area, which is where catalysis occurs. The remaining modest differences between the two catalysts are likely due to geometric effects as Hammett slopes show no evidence for electronic differences between the Au particles on the different materials.

Histone Acetyltransferase p300 Induces De Novo Super-Enhancers to Drive Cellular Senescence.

Accumulation of senescent cells during aging contributes to chronic inflammation and age-related diseases. While senescence is associated with profound alterations of the epigenome, a systematic view of epigenetic factors in regulating senescence is lacking. Here, we curated a library of short hairpin RNAs for targeted silencing of all known epigenetic proteins and performed a high-throughput screen to identify key candidates whose downregulation can delay replicative senescence of primary human cells. This screen identified multiple new players including the histone acetyltransferase p300 that was found to be a primary driver of the senescent phenotype. p300, but not the paralogous CBP, induces a dynamic hyper-acetylated chromatin state and promotes the formation of active enhancer elements in the non-coding genome, leading to a senescence-specific gene expression program. Our work illustrates a causal role of histone acetyltransferases and acetylation in senescence and suggests p300 as a potential therapeutic target for senescence and age-related diseases.

Ubinuclein-1 confers histone H3.3-specific-binding by the HIRA histone chaperone complex.

Histone chaperones bind specific histones to mediate their storage, eviction or deposition from/or into chromatin. The HIRA histone chaperone complex, composed of HIRA, ubinuclein-1 (UBN1) and CABIN1, cooperates with the histone chaperone ASF1a to mediate H3.3-specific binding and chromatin deposition. Here we demonstrate that the conserved UBN1 Hpc2-related domain (HRD) is a novel H3.3-specific-binding domain. Biochemical and biophysical studies show the UBN1-HRD preferentially binds H3.3/H4 over H3.1/H4. X-ray crystallographic and mutational studies reveal that conserved residues within the UBN1-HRD and H3.3 G90 as key determinants of UBN1-H3.3-binding specificity. Comparison of the structure with the unrelated H3.3-specific chaperone DAXX reveals nearly identical points of contact between the chaperone and histone in the proximity of H3.3 G90, although the mechanism for H3.3 G90 recognition appears to be distinct. This study points to UBN1 as the determinant of H3.3-specific binding and deposition by the HIRA complex.

miR-211 is a prosurvival microRNA that regulates chop expression in a PERK-dependent manner.

MicroRNAs typically function at the level of posttranscriptional gene silencing within the cytoplasm; however, increasing evidence suggests that they may also function in nuclear, Argonaut-containing complexes, to directly repress target gene transcription. We have investigated the role of microRNAs in mediating endoplasmic reticulum (ER) stress responses. ER stress triggers the activation of three signaling molecules: Ire-1α/ß, PERK, and ATF6, whose function is to facilitate adaption to the ensuing stress. We demonstrate that PERK induces miR-211, which in turn attenuates stress-dependent expression of the proapoptotic transcription factor chop/gadd153. MiR-211 directly targets the proximal chop/gadd153 promoter, where it increases histone methylation and represses chop expression. Maximal chop accumulation ultimately correlates with miR-211 downregulation. Our data suggest a model in which PERK-dependent miR-211 induction prevents premature chop accumulation and thereby provides a window of opportunity for the cell to re-establish homeostasis prior to apoptotic commitment.

Heterobifunctional PEGs: efficient synthetic strategies and useful conjugation methodologies.

The desire to develop nanoparticle and liposomal formulations as drug carriers capitalizing on active transport mechanisms requires constant development of novel heterobifunctional polyethyleneglycol (PEG) constructs. Such constructs should be capable of sequentially reacting with extracellular binding ligands and structural components of nanoparticles and/or liposomes. This paper describes two syntheses of heterobifunctional PEGs useful for tethering small molecule ligands to synthetic lysine-bearing polymers.

PTP1B inhibitors: synthesis and evaluation of difluoro-methylenephosphonate bioisosteres on a sulfonamide scaffold.

We have synthesized and evaluated a series of triaryl sulfonamide-based PTP1B inhibitors in which a difluoro-methylenephosphonate group of a potent lead has been replaced by potential bioisosteric replacements. Several mono- or di-charged compounds (8a, 8b, and 15a) were shown exhibit inhibitory activity in the low micromolar range, demonstrating the feasibility of using this approach in identifying non-phosphonate pTyr mimetics in a small molecular scaffold. These results also provide a useful indication of the relative effectiveness of these pTyr mimetics.

Discovery and structure-activity relationships of novel sulfonamides as potent PTP1B inhibitors.

A series of novel sulfonamides containing a single difluoromethylene-phosphonate group were discovered to be potent inhibitors of protein tyrosine phosphatase 1B. Structure-activity relationships around the scaffold were investigated, leading to the identification of compounds with IC50 or Ki values in the low nanomolar range. These sulfonamide-based inhibitors exhibit 100 and 30 times higher inhibitory activity than the corresponding tertiary amines and carboxamides, respectively.