Simulated structure and imaging of NTCDI on Si(1 1 1)-7 × 7 : a combined STM, NC-AFM and DFT study

The adsorption of naphthalene tetracarboxylic diimide (NTCDI) on Si(1 1 1)-7 × 7 is investigated through a combination of scanning tunnelling microscopy (STM), noncontact atomic force microscopy (NC-AFM) and density functional theory (DFT) calculations. We show that NTCDI adopts multiple planar adsorption geometries on the Si(1 1 1)-7 × 7 surface which can be imaged with intramolecular bond resolution using NC-AFM. DFT calculations reveal adsorption is dominated by covalent bond formation between the molecular oxygen atoms and the surface silicon adatoms. The chemisorption of the molecule is found to induce subtle distortions to the molecular structure, which are observed in NC-AFM images

MicroRNA regulation of the paired-box transcription factor Pax3 confers robustness to developmental timing of myogenesis

Commitment of progenitors in the dermomyotome to myoblast fate is the first step in establishing the body musculature. Pax3 is a crucial transcription factor, important for skeletal muscle development and expressed in myogenic progenitors in the dermomyotome of developing somites and in migratory muscle progenitors that populate the limb buds. Down-regulation of Pax3 is essential to ignite the myogenic program, including up-regulation of myogenic regulators, Myf-5 and MyoD. MicroRNAs (miRNAs) confer robustness to developmental timing by posttranscriptional repression of genetic programs that are related to previous developmental stages or to alternative cell fates. Here we demonstrate that the muscle-specific miRNAs miR-1 and miR-206 directly target Pax3. Antagomir-mediated inhibition of miR-1/miR-206 led to delayed myogenic differentiation in developing somites, as shown by transient loss of myogenin expression. This correlated with increased Pax3 and was phenocopied using Pax3-specific target protectors. Loss of myogenin after antagomir injection was rescued by Pax3 knockdown using a splice morpholino, suggesting that miR-1/miR-206 control somite myogenesis primarily through interactions with Pax3. Our studies reveal an important role for miR-1/miR-206 in providing precision to the timing of somite myogenesis. We propose that posttranscriptional control of Pax3 downstream of miR-1/miR-206 is required to stabilize myoblast commitment and subsequent differentiation. Given that mutually exclusive expression of miRNAs and their targets is a prevailing theme in development, our findings suggest that miRNA may provide a general mechanism for the unequivocal commitment underlying stem cell differentiation

Four selenoprotein P genes exist in salmonids : Analysis of their origin and expression following Se supplementation and bacterial infection

Acknowledgements: This research was funded by Alltech. We thank Dr. Jun Zou (Shanghai Ocean University) for the provision of the recombinant proteins and PAMPS used in this study. Data Availability: All cloned sequences as reported in this study were submitted to the GenBank database at https://www.ncbi.nlm.nih.gov/genbank/ (accession number(s) MH085053-MH085057). Funding: M.A.N.P. received funding of his PhD studies by Alltech (https://www.alltech.com/) under the grant code rg13398-10. The research yielded this manuscript. The authors can confirm the funder provided support in the form of a studentship for author M.A.N.P. and salaries for JS but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Sprouty2 mediated tuning of signalling is essential for somite myogenesis

Background: Negative regulators of signal transduction cascades play critical roles in controlling different aspects of normal embryonic development. Sprouty2 (Spry2) negatively regulates receptor tyrosine kinases (RTK) and FGF signalling and is important in differentiation, cell migration and proliferation. In vertebrate embryos, Spry2 is expressed in paraxial mesoderm and in forming somites. Expression is maintained in the myotome until late stages of somite differentiation. However, its role and mode of action during somite myogenesis is still unclear. Results: Here, we analysed chick Spry2 expression and showed that it overlaps with that of myogenic regulatory factors MyoD and Mgn. Targeted mis-expression of Spry2 led to inhibition of myogenesis, whilst its C-terminal domain led to an increased number of myogenic cells by stimulating cell proliferation. Conclusions: Spry2 is expressed in somite myotomes and its expression overlaps with myogenic regulatory factors. Overexpression and dominant-negative interference showed that Spry2 plays a crucial role in regulating chick myogenesis by fine tuning of FGF signaling through a negative feedback loop. We also propose that mir-23, mir-27 and mir-128 could be part of the negative feedback loop mechanism. Our analysis is the first to shed some light on in vivo Spry2 function during chick somite myogenesis

Flagships and tumbleweed: A history of the politics of gender justice work in Oxfam GB 1986–2015

This article contributes to scholarship on the political nature of feminists’ work in international development NGOs. The case study of Oxfam GB (OGB) is contemporary history, based on compiling a brief history of gender justice work between 1986 and 2014 and 18 months of part-time participant-observation fieldwork during 2014–15. I describe funding pressures and imperatives, contestations of meaning and power struggles within OGB and argue that gender justice becomes entangled in both internal and the external politics of international development. This is part of a wider research programme about how ideas on gender equality norms travel between and around development organizations, so I finally draw conclusions about how norms are contested and embodied. The shapeshifting political nature of feminist work challenges prevailing theories about how norms and ideas travel and take hold within organizations

Histological renal osteodystrophy, and 25 hydroxycholecalciferol and aluminum levels in patients on continuous ambulatory peritoneal dialysis

Renal osteodystrophy, which influences the quality of life and contributes to the morbidity of patients with endstage renal failure [1], has been reported to deteriorate in patients treated with continuous ambulatory peritoneal dialysis (CAPD) [2]. However, better control of serum calcium and phosphate in these patients [3] has provided preliminary data that show improvement in histological grading of osteitis fibrosa (OF) in our patients treated with CAPD [41.Another form of bone disease, the osteomalacic dialysis osteodystrophy (OM), which may be associated with dialysis encephalopathy, is thought in some instances to be due to aluminum toxicity [5] from untreated or softened water used in hemodialysis in areas where the aluminum content of water supplies is high [6]. In patients undergoing CAPD any exposure to aluminum is likely to stem from the use of aluminum-containing phosphate binders (ACPB) since the process of preparation of peritoneal dialysis fluid reduces most of the trace metals.In our unit, since the inception of the CAPD program in January 1979, 72 patients have been treated by this method in the first 2 years. In this report we present data on the improvement of histological renal osteodystrophy in CAPD patients and relate this to serum concentrations of calcium, phosphate, 25 hydroxycholecalciferol [25-(0H)CC] and immunoreactive parathormone (PTH). In addition, sequential serum aluminum concentrations are reported. These levels have been related to concentrations of aluminum in the peritoneal dialysis (PD) fluid and to the use of ACPB. One patient with aluminum toxicity prior to starting CAPD was studied to evaluate the chelating effect of disferrioxamine (DFO) on aluminum and its subsequent removal in the PD fluid

SALL4 Expression in Gonocytes and Spermatogonial Clones of Postnatal Mouse Testes

The spermatogenic lineage is established after birth when gonocytes migrate to the basement membrane of seminiferous tubules and give rise to spermatogonial stem cells (SSC). In adults, SSCs reside within the population of undifferentiated spermatogonia (Aundiff) that expands clonally from single cells (Asingle) to form pairs (Apaired) and chains of 4, 8 and 16 Aaligned spermatogonia. Although stem cell activity is thought to reside in the population of Asingle spermatogonia, new research suggests that clone size alone does not define the stem cell pool. The mechanisms that regulate self-renewal and differentiation fate decisions are poorly understood due to limited availability of experimental tools that distinguish the products of those fate decisions. The pluripotency factor SALL4 (sal-like protein 4) is implicated in stem cell maintenance and patterning in many organs during embryonic development, but expression becomes restricted to the gonads after birth. We analyzed the expression of SALL4 in the mouse testis during the first weeks after birth and in adult seminiferous tubules. In newborn mice, the isoform SALL4B is expressed in quiescent gonocytes at postnatal day 0 (PND0) and SALL4A is upregulated at PND7 when gonocytes have colonized the basement membrane and given rise to spermatogonia. During steady-state spermatogenesis in adult testes, SALL4 expression overlapped substantially with PLZF and LIN28 in Asingle, Apaired and Aaligned spermatogonia and therefore appears to be a marker of undifferentiated spermatogonia in mice. In contrast, co-expression of SALL4 with GFRα1 and cKIT identified distinct subpopulations of Aundiff in all clone sizes that might provide clues about SSC regulation. Collectively, these results indicate that 1) SALL4 isoforms are differentially expressed at the initiation of spermatogenesis, 2) SALL4 is expressed in undifferentiated spermatogonia in adult testes and 3) SALL4 co-staining with GFRα1 and cKIT reveals distinct subpopulations of Aundiff spermatogonia that merit further investigation. © 2013 Gassei, Orwig

Inositol 1,3,4,5,6-pentakisphosphate 2-kinase is a distant IPK member with a singular inositide binding site for axial 2-OH recognition

Inositol phosphates (InsPs) are signaling molecules with multiple roles in cells. In particular Graphic (InsP6) is involved in mRNA export and editing or chromatin remodeling among other events. InsP6 accumulates as mixed salts (phytate) in storage tissues of plants and plays a key role in their physiology. Human diets that are exclusively grain-based provide an excess of InsP6 that, through chelation of metal ions, may have a detrimental effect on human health. Ins(1,3,4,5,6)P5 2-kinase (InsP5 2-kinase or Ipk1) catalyses the synthesis of InsP6 from InsP5 and ATP, and is the only enzyme that transfers a phosphate group to the axial 2-OH of the myo-inositide. We present the first structure for an InsP5 2-kinase in complex with both substrates and products. This enzyme presents a singular structural region for inositide binding that encompasses almost half of the protein. The key residues in substrate binding are identified, with Asp368 being responsible for recognition of the axial 2-OH. This study sheds light on the unique molecular mechanism for the synthesis of the precursor of inositol pyrophosphates

Unique determination of “subatomic” contrast by imaging covalent backbonding

The origin of so-called “subatomic” resolution in dynamic force microscopy has remained controversial since its first observation in 2000. A number of detailed experimental and theoretical studies have identified different possible physicochemical mechanisms potentially giving rise to subatomic contrast. In this study, for the first time we are able to assign the origin of a specific instance of subatomic contrast as being due to the back bonding of a surface atom in the tip−sample junction

Non-stationary dynamic analysis of a wind turbine power drivetrain: Offshore considerations

This paper presents a multi-body model for studying the non-stationary dynamic behaviour of a wind turbine power drivetrain. The model includes some offshore considerations, such as the extra degrees of freedom and boundary conditions that installation on an offshore floating platform can add. The studied problem is an offshore implementation, with seafloor depths of the order of a hundred metres, making it necessary to use a floating platform. Special attention is paid to the characteristics of the combined offshore buoy support and detailed model of the power train, in order to assess the impacts of buoy movement on forces on gears and bearings. A multi-body analysis code was used to develop the model, and a conventional wind turbine set-up was implemented as an example. Gearbox dynamic behaviour was simulated for common manoeuvres such as a start-up and an emergency stop, and the results are presented and discussed.The authors like to thanks the company Apia XXI for supporting part of the research presented by the Project DINAER. Moreover, some parts of the developments presented have been made in the framework of Project DPI2006-14348 funded by the Spanish Ministry of Science and Technology