Age-related changes in murine myometrial transcript profile are mediated by exposure to the female sex hormones.

In humans, the risk of operative first delivery increases linearly with maternal age. We previously hypothesized that prolonged, cyclical, prepregnancy exposure to estrogen and progesterone contributes to uterine aging. Here, we test this hypothesis. Myometrium was obtained from four groups of virgin mice: (i) 10- to 12-week- and 28- to 30-week-old mice; (ii) 10- to 12-week- and 38- to 40-week-old mice; (iii) 38-week-old mice that had an ovariectomy or sham operation early in life; (iv) 38-week-old mice that had been treated with progesterone or vehicle containing implants from 8 to 36 weeks. Transcript profiling was carried out using Affymetrix Gene ST 1.1 arrays, and data were normalized. We identified 60 differentially regulated transcripts associated with advancing age (group 1). We validated these changes in group 2 (P for overlap = 5.8 × 10(-46) ). Early ovariectomy prevented the age-related changes in myometrial transcript profile. Similarly, progesterone-mediated long-term ovarian suppression prevented the age-related changes in myometrial transcript profile. Interferon regulatory factor 7 (Irf7) mRNA was regulated by age and hormonal exposure, and was identified as a predicted regulator of the other differentially expressed transcripts by both promoter sequence and canonical pathway activation analysis (P = 8.47 × 10(-5) and P < 10(-10) , respectively). Immunohistochemistry demonstrated IRF7 in both mouse and human myometrium. We conclude the following: (i) Myometrial aging in mice is associated with reproducible changes in transcript profile; (ii) these changes can be prevented by interventions which inhibit cyclical changes in the female sex hormones; and (iii) IRF7 may be an important regulator of myometrial function and aging.This work was supported by the NIHR Cambridge Comprehensive Biomedical Research Centre, Addenbrooke's Charitable Trust and the Evelyn Trust.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1111/acel.1240

Site-specific incorporation of phosphotyrosine using an expanded genetic code.

Access to phosphoproteins with stoichiometric and site-specific phosphorylation status is key to understanding the role of protein phosphorylation. Here we report an efficient method to generate pure, active phosphotyrosine-containing proteins by genetically encoding a stable phosphotyrosine analog that is convertible to native phosphotyrosine. We demonstrate its general compatibility with proteins of various sizes, phosphotyrosine sites and functions, and reveal a possible role of tyrosine phosphorylation in negative regulation of ubiquitination

Synergistic effects of dual-electrocatalyst FeOOH/NiOOH thin films as effective surface photogenerated hole extractors on a novel hierarchical heterojunction photoanode structure for solar-driven photoelectrochemical water splitting

Herein, we report the rational design of a novel hierarchical V2O5/BiVO4 heterojunction photoanode structure with rGO interlayer that functionalises as photogenerated electron collector, and dual electrocatalyst thin films of FeOOH and NiOOH as photogenerated hole extractors for solar-driven PEC water splitting. Results showed that the novel hierarchical FTO/V2O5/rGO/BiVO4/FeOOH/NiOOH photoanode exhibited an unprecedented and stable photocurrent density of 3.06 mA/cm2 at 1.5 V vs Ag/AgCl, and an apparent cathodic onset potential shift down to 0.2 V under AM 1.5 G simulated solar light illumination. The significant enhancement in PEC performance is ascribed to band potentials matching between V2O5 and BiVO4 in forming a Type II staggered heterojunction alignment, and further coupling with rGO interlayer and dual-electrocatalyst thin films as photogenerated electron collector and photogenerated hole extractors, respectively. Three different configurations of the novel hierarchical FTO/V2O5/rGO/BiVO4 photoanodes without electrocatalyst, with mono- and dual-electrocatalyst thin films were systematically examined. It was proven though EIS and IMPS measurements that the dual-electrocatalyst configuration photoanode exhibited the shortest transit time (τ) of 31.8 ms for the diffusion of photogenerated electrons to the counter electrode, and the lowest charge transfer resistance across the interface of electrode/electrolyte as estimated using the Randles-Ershel model. We believe that the proof-of-principle work described here not only provides an in-depth understanding on the roles of electrocatalyst thin films but also provides a design guide over the incorporation of electrocatalyst materials for further improving the photogenerated charge carrier dynamics in photoanodes used in solar-driven PEC water splitting

A Type II n-n staggered orthorhombic V2O5/monoclinic clinobisvanite BiVO4 heterojunction photoanode for photoelectrochemical water oxidation: Fabrication, characterisation and experimental validation

Conventional photoanode using a singular semiconductor material is not technically viable for photoelectrochemical (PEC) water oxidation owing to the properties relating to its wide band gap, sluggish charge mobility, as well as poor separation and rapid recombination of photogenerated charge carriers. The main aim of this study was to fabricate an n-n heterojunction photoanode of V2O5/BiVO4 via a facile electrodeposition synthesis method in order to overcome the technical bottlenecks encountered in conventional singular photoanode structures. Additionally, the synergistic effect of band potentials matching and conductivity difference between BiVO4 and V2O5 were studied using LSV, IMPS, EIS, HR-TEM, XRD, XPS, Raman and ultraviolet-visible spectroscopies. This was followed by the performance evaluation of the light-induced water splitting using a standard three-electrode assembly PEC cell under 1.5 AM solar simulator. Results showed that the V2O5/BiVO4 heterojunction photoanode achieved a significantly improved photocurrent density of 1.53 mA/cm2 at 1.5 V vs Ag/AgCl, which was a 6.9-fold and a 7.3-fold improvement over the individual pristine BiVO4 (0.22 mA/cm2) and V2O5 (0.21 mA/cm2), respectively. The improvement was attributed to the lower charge resistances at the FTO/semiconductor, semiconductor/FTO and semiconductor/electrolyte interfaces as well as the fast transit time () of 6.4 ms for photo-injected electrons in the V2O5/BiVO4 heterojunction photoanode. Finally, the experimental results were used to reconstruct a theoretical band diagram in validating the heterojunction alignment between V2O5 and BiVO4 as well as in elucidating the photogenerated charge carriers transfer mechanism in the V2O5/BiVO4 heterojunction photoanode

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Tuning of reduced graphene oxide thin film as an efficient electron conductive interlayer in a proven heterojunction photoanode for solar-driven photoelectrochemical water splitting

Although bismuth vanadate (BiVO4) has shown excellent photoelectrochemical (PEC) properties and is a good candidate of photoanode materials, the solar-driven PEC water splitting performance is still remained below its full potential due to the fast recombination and sluggish charge mobility of photogenerated charge carriers. Previously, we have communicated a proven Type II staggered vanadium pentoxide (V2O5)/BiVO4 heterojunction photoanode that could improve the photocurrent density. This study aimed to examine the effect of introducing an rGO thin film as an efficient electron conductive interlayer in a proven V2O5/BiVO4 heterojunction photoanode, and subsequently tuning the rGO film thickness in achieving the optimum PEC performance. The resultant ternary photoanode structure of V2O5/rGO/BiVO4 was characterised by using field emission-scanning electron microscopy (FE-SEM), high resolution-transmission electron microscopy (HR-TEM), UV–vis spectroscopy, X-ray diffractometer (XRD), Raman spectroscopy and photoluminescence (PL) measurements. Results showed that the interlayer rGO thin film arising from the sequential drop cast and electrochemical reduction of 320 μL ultrasonicated GO solution resulted in the optimal photocurrent density of 2.1 mA/cm2 at 1.5 V vs. Ag/AgCl. Furthermore, the chemical physics surrounding the photogenerated charge carrier transfer for heterojunction V2O5/BiVO4 was validated for the structure with and without the rGO interlayer. In particular, the electrochemical impedance spectroscopy (EIS) was used to measure multiple resistances at the FTO/semiconductor, semiconductor/semiconductor and semiconductor/electrolyte interfaces. Additionally, the charge transfer (Kt) and recombination (Kr) rate constants for the heterojunction V2O5/BiVO4 with the rGO interlayer were quantified using intensity modulated photocurrent spectroscopy (IMPS). Finally, the PEC H2 evolution rate from the ternary V2O5/rGO/BiVO4 photoanode was measured to be 32.7 μ mol/hr, which was about 3-fold higher than the bare V2O5/BiVO4 heterojunction photoanode

Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue

It’s not the size, it’s the relationship: from ‘small states’ to asymmetry

Debate about the definition of “small state” has produced more fragmentation than consensus, even as the literature has demonstrated its subjects’ roles in joining international organizations propagating norms, executing creative diplomacy, influencing allies, avoiding and joining conflicts, and building peace. However, work on small states has struggled to identify commonalities in these states’ international relations, to cumulate knowledge, or to impact broader IR theory. This paper advocates a changed conceptual and definitional framework. Analysis of “small states” should pivot to examine the dynamics of the asymmetrical relationships in which these states are engaged. Instead of seeking an overall metric for size as the relevant variable—falling victim in a different way Dahl’s “lump-of-power fallacy,” we can recognize the multifaceted, variegated nature of power, whether in war or peacetime

Energy generation from palm oil mill effluent: A life cycle assessment of two biogas technologies

© 2019 This study conducted a life cycle assessment of palm oil mill effluent (POME) based energy generation using the CML 2001 method and Gabi 8 software, focusing on two POME treatment technologies: the covered lagoon bio-digester (CLB) and the continuous stirred tank reactor (CSTR). The analysis determined the respective environmental impacts of the technologies, both of which are currently in use in Malaysia. The global warming potential (GWP) and acidification potential (AP) for CSTR were −4.48 kg CO2 eq/kWh and −2.21 kg SO2 eq/kWh respectively, while for CLB the values were −4.09 kg CO2 eq/kWh and −0.15 kg SO2 eq/kWh. Both technologies produced a negative result, which equates to a net environmental benefit. However, both systems had a negative impact in terms of eutrophication potential (EP). The CSTR nevertheless achieved a better EP result of 0.048 kg PO43− eq/kWh than the CLB with 0.054 kg PO43− eq/kWh. A sensitivity analysis was carried out in order to find a way to overcome the impacts of EP. The findings provide useful data to guide decision-makers in the sustainable management of POME, in Malaysia and globally where similar technologies are in use

Structural basis of dimerization and nucleic acid binding of human DBHS proteins NONO and PSPC1.

The Drosophila behaviour/human splicing (DBHS) proteins are a family of RNA/DNA binding cofactors liable for a range of cellular processes. DBHS proteins include the non-POU domain-containing octamer-binding protein (NONO) and paraspeckle protein component 1 (PSPC1), proteins capable of forming combinatorial dimers. Here, we describe the crystal structures of the human NONO and PSPC1 homodimers, representing uncharacterized DBHS dimerization states. The structures reveal a set of conserved contacts and structural plasticity within the dimerization interface that provide a rationale for dimer selectivity between DBHS paralogues. In addition, solution X-ray scattering and accompanying biochemical experiments describe a mechanism of cooperative RNA recognition by the NONO homodimer. Nucleic acid binding is reliant on RRM1, and appears to be affected by the orientation of RRM1, influenced by a newly identified 'β-clasp' structure. Our structures shed light on the molecular determinants for DBHS homo- and heterodimerization and provide a basis for understanding how DBHS proteins cooperatively recognize a broad spectrum of RNA targets