Non-Classical HLA Determinants of the Clinical Response after Autologous Stem Cell Transplantation for Systemic Sclerosis

Systemic Sclerosis (SSc) is a chronic autoimmune disease with high morbidity and mortality. Autologous Hematopoietic Stem Cell Transplantation (AHSCT) is the best therapeutic option for rapidly progressive SSc, allowing increased survival with regression of skin and lung fibrosis. The immune determinants of the clinical response after AHSCT have yet to be well characterized. In particular, the pivotal role of the Human Leukocyte Antigen (HLA) system is not well understood, including the role of non-classical immuno-modulatory HLA-E and HLA-G molecules in developing tolerance and the role of Natural Killer cells (NK) in the immunomodulation processes. We retrospectively tested whether the genetic and/or circulating expression of the non-classical HLA-E and HLA-G loci, as well as the imputed classical HLA determinants of HLA-E expression, influence the observed clinical response to AHSCT at 12- and 24-month follow-up. In a phenotypically well-defined sample of 46 SSc patients classified as clinical responders or non-responders, we performed HLA genotyping using next-generation sequencing and circulating levels of HLA-G and quantified HLA-E soluble isoforms by ELISA. The -21HLA-B leader peptide dimorphism and the differential expression level of HLA-A and HLA-C alleles were imputed. We observed a strong trend towards better clinical response in HLA-E*01:03 or HLA-G 14bp Del allele carriers, which are known to be associated with high expression of the corresponding molecules. At 12-month post-AHSCT follow-up, higher circulating levels of soluble HLA-E were associated with higher values of modified Rodnan Skin Score (mRSS) (p = 0.0275), a proxy of disease severity. In the non-responder group, the majority of patients carried a double dose of the HLA-B Threonine leader peptide, suggesting a non-efficient inhibitory effect of the HLA-E molecules. We did not find any correlation between the soluble HLA-G levels and the observed clinical response after AHSCT. High imputed expression levels of HLA-C alleles, reflecting more efficient NK cell inhibition, correlated with low values of the mRSS 3 months after AHSCT (p = 0.0087). This first pilot analysis of HLA-E and HLA-G immuno-modulatory molecules suggests that efficient inhibition of NK cells contributes to clinical response after AHSCT for SSc. Further studies are warranted in larger patient cohorts to confirm our results.     

Control of Switching Modes and Conductance Quantization in Oxygen Engineered HfOx based Memristive Devices

Hafnium oxide (HfO_x)‐based memristive devices have tremendous potential as nonvolatile resistive random access memory (RRAM) and in neuromorphic electronics. Despite its seemingly simple two‐terminal structure, a myriad of RRAM devices reported in the rapidly growing literature exhibit rather complex resistive switching behaviors. Using Pt/HfO_x/TiN‐based metal–insulator–metal structures as model systems, it is shown that a well‐controlled oxygen stoichiometry governs the filament formation and the occurrence of multiple switching modes. The oxygen vacancy concentration is found to be the key factor in manipulating the balance between electric field and Joule heating during formation, rupture (reset), and reformation (set) of the conductive filaments in the dielectric. In addition, the engineering of oxygen vacancies stabilizes atomic size filament constrictions exhibiting integer and half‐integer conductance quantization at room temperature during set and reset. Identifying the materials conditions of different switching modes and conductance quantization contributes to a unified switching model correlating structural and functional properties of RRAM materials. The possibility to engineer the oxygen stoichiometry in HfO_x will allow creating quantum point contacts with multiple conductance quanta as a first step toward multilevel memristive quantum devices.     

Is correspondence reflected in the author position? A bibliometric study of the relation between corresponding author and byline position

Bibliometric indicators are increasingly used to fund and evaluate scientific research. Since the number of authors in a paper and the number of has increased it is difficult to determine the individual contribution of authors. Suggested approaches include the study of author position or the corresponding author. Our findings show that the corresponding author is most likely to appear first and then last in the byline. The results are dependent on number of authors in a paper and national differences exist. This underscores the need to take into account both the number of authors on a paper and their position in the byline to be accurate when measuring author contribution.     

Invited review: Disentangling residual feed intake—Insights and approaches to make it more fit for purpose in the modern context

Residual feed intake (RFI) is an increasingly used trait to analyze feed efficiency in livestock, and in some sectors such as dairy cattle, it is one of the most frequently used traits. Although the principle for calculating RFI is always the same (i.e., using the residual of a regression of intake on performance predictors), a wide range of models are found in the literature, with different predictors, different ways of considering intake, and more recently, different statistical approaches. Consequently, the results are not easily comparable from one study to another as they reflect different biological variabilities, and the relationship between the residual (i.e., RFI) and the underlying true efficiency also differs. In this review, the components of the RFI equation are explored with respect to the underlying biological processes. The aim of this decomposition is to provide a better understanding of which of the processes in this complex trait contribute significantly to the individual variability in efficiency. The intricacies associated with the residual term, as well as the energy sinks and the intake term, are broken down and discussed. Based on this exploration as well as on some recent literature, new forms of the RFI equation are proposed to better separate the efficiency terms from errors and inaccuracies. The review also considers the time period of measurement of RFI. This is a key consideration for the accuracy of the RFI estimation itself, and also for understanding the relationships between short-term efficiency, animal resilience, and long-term efficiency. As livestock production moves toward sustainable efficiency, these considerations are increasingly important to bring to bear in RFI estimations.     

How climate-smart is conservation agriculture (CA)? – its potential to deliver on adaptation,mitigation and productivity on smallholder farms in southern Africa

Climate resilient cropping systems are required to adapt to the increasing threats of climate change projected for Southern Africa and to better manage current climate variability. Conservation agriculture (CA) has been proposed among technologies that are climate-smart. For a cropping system to be labelled “climate-smart” it has to deliver three benefits: a) adapt to the effects of climate and be of increased resilience; b) mitigate climate effects by sequestering carbon (C) and reducing greenhouse gas emissions (GHG); and c) sustainably increase productivity and income. Research on smallholder farms from Southern Africa was analysed to assess if CA can deliver on the three principles of climate-smart agriculture. Results from Southern Africa showed that CA systems have a positive effect on adaptation and productivity, but its mitigation potential lags far behind expectations. CA systems maintain higher infiltration rates and conserve soil moisture, which helps to overcome seasonal dry-spells. Increased productivity and profitability were recorded although a lag period of 2–5 cropping seasons is common until yield benefits become significant. Immediate economic benefits such as reduced labour requirements in some systems will make CA more attractive in the short term to farmers who cannot afford to wait for several seasons until yield benefits accrue. The available data summarizing the effects of CA on soil organic C (SOC) and reductions in greenhouse gases, are often contradictory and depend a great deal on the agro-ecological environment and the available biomass for surface residue retention. There is an urgent need for more research to better quantify the mitigation effects, as the current data are scanty. Possible co-interventions such as improved intercropping/relay cropping systems, agroforestry and other tree-based systems may improve delivery of mitigation benefits and need further exploration.     

Demographic, clinical, and neurocognitive correlates of everyday functional impairment in severe mental illness.

Although cognitive deficits often accompany severe mental illness, their implications for everyday functioning remain poorly understood. In this study, an occupational therapist (OT) rated the everyday functioning of 105 adult psychiatric patients. Using demographic, clinical, and cognitive variables, the authors tested alternative models to account for the observed variability in OT ratings. Although age, education, and the presence of schizophrenia each contributed to a model that accounted for 27% of the variation in functional independence, adding terms for auditory divided attention and verbal learning increased the proportion of explained variance to 45% and decreased the beta weights for age and education—but not schizophrenia—to nonsignificant levels. These findings demonstrate the relevance of cognitive performance to everyday functioning in severe mental illness. They are discussed with respect to hypothesized determinants of psychiatric disability. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Tailoring the morphology and properties of poly(lactic acid)/poly(ethylene)‐co‐(vinyl acetate)/starch blends via reactive compatibilization

Poly(lactic acid)/poly(ethylene‐co‐vinyl acetate)/starch (PLA/EVA/starch) ternary blends were prepared by multi‐step melt processing (reactive extrusion) in the presence of maleic anhydride (MA), benzoyl peroxide and glycerol. The effects of MA and glycerol concentration on the morphology and properties of the PLA/EVA/starch blends were studied using scanning electron microscopy, transmission electron microscopy, atomic force microscopy, the Molau experiment, dynamic mechanical thermal analysis and differential scanning calorimetry etc. The plasticization and compatibilization provided a synergistic effect to these blends accompanied by a significant reduction in starch particle size and an increase in interfacial adhesion. Starch was finely dispersed in the ternary blends with a dimension of 0.5 ? 2 µm. Furthermore, EVA‐coated starch or a starch‐in‐EVA type of morphology was observed for the reactively compatibilized PLA/EVA/starch blends. The EVA with starch gradually changed into a co‐continuous phase with increasing MA concentration. Consequently, the toughness of the blends was improved. Since property stability of starch is an issue, the tensile properties of these blends were measured after different storage times and the blends showed good property stability. Copyright © 2012 Society of Chemical Industry     

Insights into Carbopol gel formulations: Microscopy analysis of the microstructure and the influence of polyol additives

Carbopol is a family of high molecular weight cross‐linked poyacrylic acids widely used as thickening agents in several industrial applications. In this work, the structure of Carbopol 974P NF was investigated at pH 7.4 by means of capillary viscometry, dynamic rheology, fluorescence microscopy, and electron microscopy in the dilute and semi‐dilute (hydrogel) state. Especially, high‐pressure freezing technique has proved to be a technique of choice to visualize the Carbopol hydrogel microstructure through cryo‐scanning electron microscopy analysis without artifacts related to the formation of ice crystals. It has been shown that the Carbopol hydrogel has a hierarchical structure made of large spherical entities of a few micrometers in size packed together and composed of much smaller agglomerated microgel particles. In addition, fluorescence and electron microscopies have pointed out that the presence of polyol additives in the gel formulation favors the formation of more dense or jammed structure, probably through hydrogen bonding. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42761.     

Changes in protein synthesis during thermal adaptation of Propionibacterium freudenreichii subsp. shermanii

Dairy propionibacteria are present in Graviera Kritis, a traditional Gruyère-type cheese made without added propionic starter. Ten isolated strains were identified by a combination of SDS-PAGE, species-specific PCR and according to their ability to ferment lactose. They were all found to belong to the Propionibacterium freudenreichii subsp. shermanii species. Because of the stressing Gruyère technology, which includes cooking at 52 to 53 degrees C their thermotolerance was investigated at 55 degrees C. Thermotolerant and thermosensitive strains were clearly discriminated. Interestingly, the reference strain CIP 103027 belongs to the sensitive subset. One sensitive strain, ACA-DC 1305 and one tolerant, ACA-DC 1451, were selected for further study and compared to CIP 103027. For the sensitive strains ACA-DC 1305 and CIP 103027, heat pre-treatment at 42 degrees C conferred thermoprotection of cells at the lethal temperature of 55 degrees C, while there was less effect on the tolerant ACA-DC 1451. No cross-protection of salt-adapted cells against heat stress was observed for none of the strains. Differential proteomic analysis revealed distinct but overlapping cell responses to heat stress between sensitive and tolerant strains. Thermal adaptation upregulated typical HSPs involved in protein repair or turnover in the sensitive one. In the tolerant one, a distinct subset of proteins was overexpressed, whatever the temperature used, in addition to HSPs. This included enzymes involved in propionic fermentation, amino acid metabolism, oxidative stress remediation and nucleotide phosphorylation. These results bring new insights into thermoprotection in propionibacteria and the occurrence of divergent phenotypes within a same subspecies.