Donor Contribution Research Articles

How Cr doping influences on the properties of ZnO nanoparticles obtained by aqueous synthesis: Exploring at low Cr concentrations

A detailed physico-chemical study of Cr3+-doped ZnO nanoparticles (NPs) obtained via aqueous synthesis was carried out. The NPs acquire greenish tonality as the Cr concentration increased. High efficiency of Cr incorporation into the ZnO lattice was found up to approximately 1 at% Cr. The ZnO:Cr NPs show wurtzite hexagonal phase with a lattice compressed for low Cr concentration and tensed for higher concentrations. Structural, chemical and optical analyses indicate that for low Cr concentration Cr occupies the Zn vacancy sites, owing to the reduction in acceptor compensation by passivating the Zn vacancies and the contribution of the unpaired electron of Cr3+, which induces an increase of electron concentration, changes in the conductivity, transport of carriers, optical properties and ferromagnetic properties, among others. At higher Cr concentrations, the passivation of Zn vacancies by Cr atoms reduces the acceptor contribution, and substantial substitution of Zn atoms by Cr atoms in the ZnO lattice strengthens the retention of O atoms in the Cr-O bonds. This results in a reduction in O vacancy concentration, donor contribution, strain, electron concentration, and luminescence intensity.

Experimental Models of Mouse and Human Hematopoietic Stem Cell Transplantation.

Experimental hematopoietic stem cell transplantation (HSCT) is an invaluable tool in determining the function and characteristics of hematopoietic stem cells (HSC) from experimental mouse and human donor groups. These groups could include, but are not limited to, genetically altered populations (gene knockout/knockin models), ex vivo manipulated cell populations, or in vivo modulated cell populations. The basic fundamentals of this process involve taking cells from a mouse/human donor source and putting them into another mouse (recipient) after preconditioning of the recipient with either total body irradiation (TBI) for mouse donor cells or into sublethally irradiated immune-deficient mice for human donor cells. Then, at pre-determined time pointspost-transplant, sampling a small amount of peripheral blood (PB) and at the termination of the evalaution, bone marrow (BM) to determine donor contribution and function by phenotypic analysis. Exploiting the congenic mouse strains of C57BL/6 (CD45.1- CD45.2+), BoyJ (CD45.1+ CD45.2-), and their F1-crossed hybrid C57BL/6×BoyJ (CD45.1+ CD45.2+), we are able to quantify donor, competitor, and recipient mouse cell contributions to the engraftment state. Human donor cell engraftment (e.g., from the cord blood [CB], mobilized PB, or BM) is assessed by human cell phenotyping in sublethally irradiated immune-deficient mouse recipients (e.g., NOD scid gamma mice that are deficient in B cells, T cells, and natural killer cells and have defective dendritic cells and macrophages). Engraftment of cells from primary mouse recipients into secondary mice allows for an estimation of the self-renewal capacity of the original donor HSC. This chapter outlines concepts, methods, and techniques for mouse and human cell models of HSCT and for assessment of donor cells collected and processed in hypoxia versus ambient air.

Frizzled-6 promotes hematopoietic stem/progenitor cell mobilization and survival during LPS-induced emergency myelopoiesis

SummaryEmergency hematopoiesis involves the activation of bone marrow hematopoietic stem/progenitor cells (HSPCs) in response to systemic inflammation by a combination of cell-autonomous and stroma-dependent signals and leads to their release from bone marrow and migration to periphery. We have previously shown that FZD6 plays a pivotal role in regulating HSPC expansion and long-term maintenance. Now we sought to better understand the underlying mechanisms. Using lipopolysaccharide (LPS)-induced emergency granulopoiesis as a model, we show that failed expansion was intrinsic to FZD6-deficient HSPCs but also required a FZD6-deficient environment. FZD6-deficient HSPCs became more strongly activated, but their mobilization to peripheral blood was impaired and they were more susceptible to inflammatory cell death, leading to enhanced release of pro-inflammatory cytokines in the marrow. These studies indicate that FZD6 has a protective effect in the bone marrow to prevent an overactive inflammatory response and further suggest that mobilization improves HSPC survival during bone marrow inflammation.

Donor Contribution to Non-Formal Education in Ghana: The Case of World Bank Support to Upper West Region

Donor Contribution to Non-Formal Education in Ghana: The Case of World Bank Support to Upper West Region

Bronchoalveolar Lavage Fluid (BALF) as a Compartment for Donor-Derived Cell-Free DNA (dd-cfDNA) Assessment in Lung Recipients

<h3>Purpose</h3> Circulating dd-cfDNA has been proposed as a biomarker to discriminate acute lung rejection. It is unknown whether BALF may represent a more sensitive compartment for dd-cfDNA analysis in lung recipients. Additionally, the relative contribution of the recipient or donor to the BALF cfDNA content remains uncertain. We sought to understand the feasibility of distinguishing dd-cfDNA in the BALF and determine the greatest contributor of BALF cfDNA. <h3>Methods</h3> The cohort was drawn from the Clinical Trials in Organ Transplantation-20 study and comprised 126 first adult lung recipients with paired BALF and plasma samples (n=320 each). Total cfDNA was isolated from ∼1mL of sample using automated nucleic acid purification. The % cfDNA contributed by the donor vs. recipient was distinguished in plasma and BALF samples using a next generation sequencing (NGS) assay that measures single nucleotide polymorphisms (SNPs) followed by bioinformatics algorithms. Because these algorithms were developed on plasma, for each BALF sample the SNP typing from the paired plasma sample was used to verify the accuracy of the donor vs. recipient cfDNA contribution in the BALF. <h3>Results</h3> Applying standard QC filters, 168 BALF samples "passed" and generated a dd-cfDNA result while 96 "failed" and did not generate a dd-cfDNA result. 45 samples yielded insufficient total cfDNA to support NGS while 11 generated a potentially invalid dd-cfDNA result. To understand reasons underlying inability to estimate BALF dd-cfDNA, we compared the volume of BALF used for total cfDNA isolation and the total cfDNA yield from the BALF in passed vs. failed samples. The BALF volume was similar between these groups, however the total cfDNA yield was notably less among samples that failed (median total cfDNA 0.38ng/uL in failed vs. 1.42ng/uL in passed samples). Considering only passed BALF samples, the median (25^th, 75^th percentile) fraction of cfDNA contributed by the donor was 6.95% (2.40%, 14.00%), with the remainder contributed by the recipient. <h3>Conclusion</h3> Our data point to challenges in consistently generating dd-cfDNA data from the BALF and suggest the dilute nature of BALF may be a contributing factor. Additionally, these results indicate that the recipient, rather than the donor, is the largest contributor to the BALF cfDNA content potentially reflecting intragraft recipient immune cells.

Postpubertal spermatogonial stem cell transplantation restores functional sperm production in rhesus monkeys irradiated before and after puberty.

Cancer treatment of prepubertal patients impacts future fertility due to the abolition of spermatogonial stem cells (SSCs). In macaques, spermatogenesis could be regenerated by intratesticular transplantation of SSCs, but no studies have involved cytotoxic treatment before puberty and transplantation after puberty, which would be the most likely clinical scenario. To evaluate donor-derived functional sperm production after SSC transplantation to adult monkeys that had received testicular irradiation during the prepubertal period. We obtained prepubertal testis tissue by unilaterally castrating six prepubertal monkeys and 2weeks later irradiated the remaining testes with 6.9Gy. However, because spermatogenic recovery was observed, we irradiated them again 14months later with 7Gy. Three of the monkeys were treated with GnRH-antagonist (GnRH-ant) for 8weeks. The cryopreserved testis cells from the castrated testes were then allogeneically transplanted into the intact testes of all monkeys. Tissues were harvested 10months later for analyses. In three of the six monkeys, 61%, 38%, and 11% of the epididymal sperm DNA were of the donor genotype. The ability to recover donor-derived sperm production was not enhanced by the GnRH-ant pretreatment. However, the extent of filling seminiferous tubules during the transplantation procedure was correlated with the eventual production of donor spermatozoa. The donor epididymal spermatozoa from the recipient with 61% donor contribution were capable of fertilizing rhesus eggs and forming embryos. Although the transplantation was done into the rete testis, two GnRH-ant-treated monkeys, which did not produce donor-derived epididymal spermatozoa, displayed irregular tubular cords in the interstitium containing testicular spermatozoa derived from the transplanted donor cells. The results further support that sperm production can be restored in non-human primates from tissues cryopreserved prior to prepubertal and post-pubertal gonadotoxic treatment by transplantation of these testicular cells after puberty into seminiferous tubules.

Use of Next Generation Sequencing and Single Nucleotide Polymorphism (SNP) Fingerprinting to Assess Post Transplant Engraftment Status

Introduction:Hematopoietic stem-cell transplantation has become an essential component of the treatment of many malignant and nonmalignant disorders in children and in adult patients. For hematologic malignancies, post transplant surveillance is often accomplished by a combination of chimerism analysis and various assays for assessment of known disease associated molecular markers. The use of several methods for disease and engraftment monitoring can be laborious and expensive and may lack sufficient sensitivity and specificity to discriminate host from donor. In this study we describe the incorporation of single nucleotide polymorphisms (SNPs) fingerprinting to assess engraftment using next generation sequencing assays that are routinely utilized for concurrent assessment of mutations in hematologic malignancies.Methods:Blood and bone marrow samples from patients undergoing monitoring for myeloid neoplasms were collected. A total of 90 samples from 32 patients were analyzed which included the diagnostic baseline host, unrelated donor and up to 6 post transplant (PT) samples from each patient. The PT samples ranged from 3 months to 2 years at various time points. NGS data from two different clinical assays were used in the study: 1) A PCR amplicon based myeloid panel capturing certain exons of 28 genes based on Raindance technology 2) MSK-IMPACT-Heme, a hybridization-capture based panel interrogating coding exons of 400 genes. While MSK-IMPACT Heme targeted 1029 polymorphic SNP loci by design, 77 highly polymorphic SNP loci were identified in the regions captured by the amplicon-based assay. Genotypes of these SNP loci were used to identify homozygous and heterozygous status in respective assays. Source and percentage of DNA contribution in the PT sample was determined using genotype information. Routine EA was performed using standard short tandem repeat (STR) analysis (Promega GammaSTR and CTTv kits.).Results:Comparison of donor contribution to the PT sample between EA and NGS assays showed very highly concordant results (R2 = 0.99, p < 0.001). Furthermore, NGS assay results were more sensitive compared to the traditional STR approach as we were able to detect low levels of host contribution in the PT sample based on the alternate alleles fractions supporting the host alleles in samples which were assessed as “all donor” by STR analysis. In addition to the clinical cases, two proficiency samples were also evaluated and the engraftment assessment showed high concordance with the known results. Data from the MSK-IMPACT-Heme assay was concordant with both Raindance assay results and STR. We randomly downsampled the 1029 different SNP loci to identify the lower limit of detection of PT status with varying number of SNPs.Conclusion:We show that NGS based assays can be used to detect engraftment status in PT samples and they can be used as a robust monitoring technique. Since they include both somatic mutation assessment in PT samples and EA in a single assay, they are a much cheaper alternative to performing multiple assays for one specimen. DisclosuresArcila:Archer: Honoraria; Raindance Tecnologies: Honoraria; Invivoscribe: Honoraria.

Non-hydrolytic sol–gel synthesis of polypropylene/TiO2 composites by reactive extrusion

An original way to synthesise polypropylene/titanium dioxide (PP/TiO2) composites combining non-hydrolytic sol–gel chemistry and reactive extrusion was reported. The non-hydrolytic sol–gel reaction between titanium alkoxide as a titanium dioxide precursor and an acid anhydride as an oxygen donor at 240 °C was first evaluated and optimised in an alkane liquid medium. TiO2 was present essentially in crystalline anatase form when synthesised in squalane with a domain size around 10 nm. Based on these encouraging results, the synthesis was adapted to reactive extrusion that means at high temperature in molten viscous polypropylene and for short reaction times (few minutes maximum). The proof of concept was evidenced through the formation of amorphous TiO2-based inorganic domains of size around 1 µm within the polymer matrix from the reaction between titanium isopropoxide and acetic anhydride. A condensation degree of 79% was obtained. To optimise the polymer/filler interface, titanium dioxide precursors and oxygen donors with different alkyl chain lengths were evaluated. Hexanoic anhydride as substituent of acetic anhydride and titanium tetrakis 2-ethylhexyloxide as substituent of titanium isopropoxide were used. The oxygen donor contribution appeared to be dominant for the particle dispersion state. The polypropylene (PP)/TiO2 composite synthesised from the reaction between titanium isopropoxide and hexanoic anhydride showed the narrowest TiO2 particle diameter distribution with a mean particle size around 700 nm.

Timing of spermatogonial stem cell transplantation affects the spermatogenic recovery outcome in mice.

Spermatogonial stem cell transplantation (SSCT) is a strategy that has demonstrated to be feasible to restore spermatogenesis in animal models when it is performed shortly after the gonadotoxic onset to destroy their endogenous germ cells. However, in the case of boys subjected to fertility preservation, future transplantations will be performed with a delay of many years. In order to study how timing of SSCT affects donor-derived spermatogenic recovery in mice, we compared the percentage of spermatogenic tubule cross-sections within testes of 59 C57BL/6NCrl mice distributed in 6 groups: group 1, untreated mice controls (n= 9); group 2, mice that received a single dose of busulfan 40mg/kg (n= 10); group 3, mice that received two additional doses of busulfan 10mg/kg every 5weeks (n= 10); group 4 (SSCT-A), mice subjected to a standard SSCT performed 5weeks after a single injection of busulfan 40mg/kg (n= 10); group 5 (SSCT-B), mice subjected to a delayed SSCT performed 15weeks after a single injection of busulfan 40mg/kg (n= 10); and group 6 (SSCT-C), mice subjected to a delayed SSCT with two additional doses of busulfan 10mg/kg every 5weeks (n= 10). Spermatogenic recovery in standard SSCT-A and SSCT-C groups ranged between 22.29 and 22.65%, compared with a lower recovery rate of 11.54% showed in the SSCT-B group. However, donor contribution resulted higher in standard SSCT-A, representing a 69.71% of cross-sections, compared with the rest of conditions ranging from 34.69 to 35.42%. Overall, we concluded that a delay in the SSCT from the gonadotoxic onset decreases the efficiency of donor-derived spermatogenic recovery in mice.

Sadaqah-Based Crowdfunding:Drivers of Muslim Donor Contribution Behavior

The concept of charitable giving through the crowdfunding platform had received significant attention from previous studies. Researchers have discussed the factors that drive the intention of donors to donate via the crowdfunding platform. However, researchers also found that the willingness to fund projects on crowdfunding platforms has been decreasing. This research aims to examine the potential of crowdfunding platform features to draw potential donors to contribute to the project. This research proposed two variables―utilitarian features (focus on functionality such as payment gateway), hedonic features (focus on enjoyment, such as the platform design). In addition, this study examined the role of trust in the platform as a mediating variable based on Stimulus - Organism – Response model (SOR) by Mehrabian &amp; Russel (1974). This research gathered 148 valid responses through the virtual snowball sampling technique, taking into consideration the early stage of Malaysia’s crowdfunding environment. The finding uncovers that the utilitarian features and trust of the platform were the significant predictors towards intention compared to hedonic features. In addition, trust in the platform managed to mediate the relationship between utilitarian features and intention but contradicts the relationship between hedonic features and intention. Theoretically, this study enriches the literature on human-computer interaction by examining the role of crowdfunding platform in attracting potential contributors. Finally, this research suggests that future studies could improve the research on the demographic and sampling methods of the respondents.

The role you play, the life you have: Donor retention in online charitable crowdfunding platform

Crowdfunding was first used by individuals and entrepreneurs to collect small-sized investments from crowds to support for-profit ventures, but now it is being touted as a valuable alternative to raise money for non-profit causes. Similar to various online settings, a key challenge for online charitable crowdfunding platform is the problem of donor retention. In this research, we disentangle donor retention behavior and build up a structural model to jointly examine donors' donation and latent attrition. By incorporating donation relationship and action related covariates into the model, we illustrate the drivers of donor retention and quantitatively examine their influence on individual donor's contribution and attrition activity. After calibrating the model with longitudinal donation transaction data from a leading charitable crowdfunding platform which enables teachers to request materials and resources for their classrooms, we find that (1) Teacher-donors (people who can be both donation makers and fundraisers) usually exhibit higher donation rate and lower attrition rate than normal donors on the platform; (2) Compared with site-donors (donors directly acquired through website visit), donors acquired through teacher referral usually have lower contribution and attrition rates; (3) The provided “charity gift card” and “donation matching offer” prosocial marketing programs on the platform seem to be a double-edged sword to donor retention. They have positive impact on donors' contribution rate, at the same time, they significantly increase donors' attrition rate; (4) Donors' initial contribution amount to the platform, successful donation result and “Thank-You” feedback from fundraisers can significantly decrease their attrition rate. Our results provide insights on new donor acquisition and donor relationship management in online charitable crowdfunding market.

Stakeholder Involvement and Performance of Donor Funded Projects in Rwanda: A Case Study of Empowering Youth Through an Inclusive Cooperative Movement in Rwanda' Project (eyicm) in Bugesera District

This study aimed at examining the role of stakeholder’s involvement on performance of donor funded project in Rwanda. The role of stakeholder participation in project performance cannot be overlooked. A review of case studies has demonstrated a relationship between the two. The study undertook to demonstrate how stakeholder participation influences the performance of donor funded projects. The study considered stakeholders’ participation in three phases of the project cycle; initiation, planning and implementation. In assessing project performance, the study was limited to two (2) key project performance indicators; timely completion and cost implication. The study was guided by three objectives: identify the influence of stakeholder participation in project initiation on project performance, understand the influence of stakeholder participation in project planning on project performance and determine the influence of stakeholder participation in project implementation on project performance. The researcher studied EYICM Project in Bugesera District, which was co-funded by European Commission and Plan International. The respondents projected representatives from donors, representatives from the implementing agency, and the project beneficiaries. Data were collected using questionnaire from project beneficiaries and interview guide from donor and implementing agency representatives. The total sample size of 75 was used in the study. Descriptive design was used to analyze data; specifically, the researcher used SPSS and mainly measures of central tendency used to describe data. The researcher correlated the dependent and independent variables in order to test the relationship between the variables. The study expressed a significant relationship between stakeholders’ engagement in project initiation and project performance where r=0.064, p&lt;0.01. in addition, the researcher found significant correlation between project acceptability by the community and performance of the project where r=-0.646, p&lt;0.01. The outcome of the study will show the extent to which stakeholders involvement at all levels of project management cycle influences the performance of donor funded projects. As a result of investigation conducted through questionnaire and interview guide, the researcher discovered that most respondents confirmed stakeholders’ participation in project initiation with 49% strongly agree and 21% agree being involved in needs assessment; 36% strongly agree and 21% agree being involved in proposing solutions; 30% strongly agree and 36% agree being involved in setting project objectives. At the level of planning, 36% strongly agreed, 14% agreed that their engagement contributed to project acceptability by the community; 40% strongly agree, 30% agreed that it created the ownership of the project by the community and lastly, at implementation level, 40% strongly agreed, 28% agreed that it created the sense of ownership of project by the community while 38% strongly agreed, 32% agreed that it contributed to community empowerment. On the basis of the study findings, the researcher made the following conclusions; The role of stakeholders’ involvement on performance of donor funded project influenced performance of EYICM project in Bugesera District. Therefore, on the influence of project management factors on the EYICM project in Bugesera District, the study concluded that the adequate institutional management skills, donor contribution, positive government policies and institutional management practices aids the performance of the EYICM Project in Bugesera District in Rwanda.

S-Genotyping and Seed Paternity Testing of the Pear Cultivar ‘Celina’

The diploid Celina/QTee® (‘Colorée de Juillet’ × ‘Williams’), one of the most promising pear cultivars developed by the Norwegian breeding program Graminor, was launched in 2010. In Norway, the flowering is medium to late, while the fruits ripen in the beginning of September. The fruits are attractive with an intense red blush (50%) on a green background. Although, ‘Celina’ is cultivated in the most climatically suitable regions for fruit cultivation, present in Norway, unfavorable environmental conditions for pear pollination can have a very negative effect on fruit set and consequent yield. The aim of this study was to determine the S-alleles of ‘Celina’, as well as its frequently used pollinizers, and, through paternity testing of ‘Celina’ seeds, give a recommendation regarding the most important pollinizers of this pear cultivar. In order to accomplish this, ‘Celina’ and its potential pollinizers were all S-genotyped. After harvest, seeds collected from ‘Celina’ fruit in 2017 and 2018 were genotyped using eleven microsatellite markers. Genomic DNA was also extracted from leaf material collected from ‘Celina’, as well as from five pear cultivars used as pollinizers in the three examined orchards, and analyzed using the same marker set. Subsequently a simple sequence repeat (SSR) database was constructed and used for gene assignment analyses with the aim of quantifying pollen donor contribution from individual pollinizers. The obtained results indicate that ‘Anna’, the only examined pollinizer that was fully cross-compatible with ‘Celina’, together with ‘Fritjof’, the genotype which had the highest flowering overlap with ‘Celina’, proved to be the most successful pollinizers across all seasons and orchards. Although both cultivars were ubiquitous in the examined orchards, either as planted trees or as branches introduced during the flowering period, they were the most abundant pollinizers in only one orchard each. It is therefore possible to conclude that pollinizer abundance has a secondary significance in pollinizer success within investigated ‘Celina’ orchards.

What determine the givers behavior? The mindset of Waqf giver in Malaysia

There are several questions that have fascinated behavioral scientists for decades; one of them was: why do we give things like money, effort, guidance, help & kind words or/and time to others? Researchers have looked into why people donate, why they don’t do it as much as they would hope to and how to bridge this gap. But no clear answer to the psychology of giving; the inner motive that drive us to give. Available literature shows that charitable giving arises from a complexity of motives, attitudes, and demographic attributes. Some may give out of altruism, while others give out of egoism. Others find mercy, humility, obligation, tax deductions, and access to elite business and social networks as motives for giving. However, what the real motivations in the highest giving individuals is not very clear, specially what is related to Waqf in Malaysia. Waqfis a financial charitable endowment established by withholding immovable and movable properties to perpetually spend its revenue on fulfilling public needs; it has been the main source for public services that been provided to communities. The purpose of this paper is to explore traits of givers, in order to present factors associated with giving behavior. A qualitative method was used to attain the study objectives. The findings signified that unique thinking and psychology behind helping others played a crucial role in donor contribution to Waqf; this concludes that sincerity determinant quality of givers.

Hepatic Leukemia Factor Is Critical for Hematopoietic Stem Cells and Promotes MLL-AF9 Acute Myeloid Leukemia

The transcription factor Hepatic leukemia factor (HLF), initially identified as part of a leukemic fusion protein (E2A-HLF) causing B-lymphoid leukemia in children, is expressed in a wide range of tissues. In the mouse hematopoietic system, HLF is highly expressed in hematopoietic stem cells while being hardly detectable in more restricted progenitor populations. We have previously shown that in adult mice, HLF is essential for preserving the hematopoietic stem cell (HSC) pool during regeneration by maintaining their quiescence (Komorowska et al, Cell reports, 2017). Notably, despite this highly specific expression profile and a critical role in hematopoietic regeneration, mice with double knock-out of HLF alleles (KO) appeared to age normally (18-24 months survival &gt; 90% for both WT and KO). In this study, we investigated the role of HLF in HSC during aging and leukemogenesis. We first confirmed that HLF is expressed all through ontogeny by performing quantitative PCR on HSC and progenitor populations from mouse fetal liver (E14.5 FL) and bone marrow (BM) of aged mice (18-month-old mice). We found that not only is HLF expressed in hematopoietic cells from embryonic to aged mice, but also that the expression profile was highly conserved. In fact, we found that HLF expression decreased during hematopoietic differentiation independently of ontogenic age (HLF/HPRT relative expression: 6 in HSC (LSK-CD150+CD48-), 3 in HSPC (LSK), and &lt;0,2 in CMP (Lin-kit+sca1-CD34+CD16/32-), GMP (Lin-kit+sca1-CD34+CD16/32+), and MEP (Lin-kit+sca1-CD34-CD16/32-). Additionally, hematopoietic parameters as well as lineage distribution in peripheral blood and bone marrow of aged KO mice were within normal range (at the exception of a 50% reduction in platelet blood count, also reported in adult mice). While we found no significant difference in the frequency of immunophenotypic HSC in total BM (LSK-CD34-Flt3-; WT: 0,0006 %, KO: 0,0004 %), aged KO grafts (200 000 total BM cells in 1:1 ratio with competitor) demonstrated a defective capacity to reconstitute primary recipients (donor contribution, WT: 60%, KO: 45 %). In secondary recipients, the defect was further aggravated (donor contribution; WT: 60 %, KO: 20%). Because neither SLAM nor CD34 markers can be used in KO FL, we quantified the percentage of EPCR+ cells within the LSK compartment as a surrogate marker for HSC and found a 2-fold decrease compared to WT controls. In competitive transplantations, KO E14.5 fetal liver cells demonstrated an impaired regenerative capacity in primary (donor contribution; WT: 88.8% (SEM 6.2), KO 63% SEM (16.2); n&gt;5) and secondary recipients (donor contribution: WT: 67% (SEM 2.7), KO: 8.4% (SEM 3.6), n=4). In addition to its function in healthy hematopoiesis, studies have suggested that HLF is a downstream mediator of the MLL/AF9 (MA9) leukemic fusion protein. To address the contribution of HLF to MA9 leukemogenesis, mice were transplanted with either KO- or WT-BM-derived c-Kit+ cells expressing the MA9 fusion protein. Preliminary results showed that HLF did not affect the latency of the leukemia in primary recipients with mice succumbing to a lethal disease at days 40-41 after transplant independently of the leukemic graft genetic background. However, KO leukemic cells had a significantly delayed leukemia development in secondary recipients (time to death; WT: 32-39 days, KO: 39-68 days). Moreover, semi-quantitative PCR showed that not only was HLF expressed in leukemia cells harvested from primary recipients but also that the expression level displayed a tendency to an increase in leukemia cells from secondary recipients. Altogether, our data suggest that while HLF may be dispensable for leukemic transformation, it promotes the development of MLL-AF9 leukemia in mice. We are currently in the process of confirming the role of HLF in MA9 leukemia development. Taken together, we here show that HLF is essential for HSCs from embryonic to aged mice. We further show that HLF is critical for serial propagation of AML cells, suggesting that HLF is needed to maintain leukemia stem cells. Disclosures No relevant conflicts of interest to declare.

Dissecting recipient from donor contribution in experimental kidney transplantation: focus on endothelial proliferation and inflammation.

ABSTRACTKidney transplantation (Tx) is considered the only definite treatment for end-stage kidney disease (ESKD) patients. The increasing prevalence of ESKD has necessitated the introduction of transplantation with kidneys from suboptimal donors. There is, however, still a lack of fundamental and longitudinal research on suboptimal kidney transplants. Specifically, there is a demand for accurate pre-Tx predictors of donor kidney function and injury to predict post-Tx outcome. In the present study, we combine rat models of chronic kidney disease (CKD) and renal Tx to dissect the effects of healthy and CKD renal grafts on healthy and CKD recipients. We show that renal function at 6 weeks post-Tx is exclusively determined by donor graft quality. Using cell tracking within enhanced green fluorescent protein-positive (eGFP+) recipients, we furthermore show that most inflammatory cells within the donor kidney originate from the donor. Oxidative and vascular extra-renal damage were, in contrast, determined by the recipient. Post- versus pre-Tx evaluation of grafts showed an increase in glomerular and peritubular capillary rarefaction in healthy but not CKD grafts within a CKD environment. Proliferation of glomerular endothelium was similar in all groups, and influx of eGFP+ recipient-derived cells occurred irrespective of graft or recipient status. Glomerular and peritubular capillary rarefaction, severity of inflammation and macrophage subtype data post-Tx were, however, determined by more complicated effects, warranting further study. Our experimental model could help to further distinguish graft from recipient environment effects, leading to new strategies to improve graft survival of suboptimal Tx kidneys.This article has an associated First Person interview with the first author of the paper.

Enhanced thermoelectric performance of SnTe: High efficient cation - anion Co-doping, hierarchical microstructure and electro-acoustic decoupling

In this work, the co-doping in both the anion and cation sites of SnTe has been implemented by addition of BiCl3 and the effect of co-doping on thermoelectric performance of SnTe-based materials has been studied detailedly. Benefitting from the sharp reduction of carrier concentration and the increase of density of states due to the electron donor contribution of Bi and Cl, the electrical transport properties have been improved greatly; moreover, the hierarchical architectures such as the point defects, dislocations, nano-particles and phase/grain boundaries act as multiscale phonon scattering centers and effectively suppress the transport of phonons in wide frequency range, thus reduced the thermal conductivity dramatically. Due to the synergistic regulation of cation-anion co-doping, a maximum ZT of ~1.27 at 873 K has been obtained in the sample of SnTe doping with 4% BiCl3, which enhances by 182% in comparison with the pristine sample.

Resilience of Malic Acid Natural Deep Eutectic Solvent Nanostructure to Solidification and Hydration.

Little is presently known about the unique nanostructure of deep eutectic solvents (DES). The order of the liquid-solid phase transition is contended and whether DES-water mixtures are merely aqueous solutions, or have properties dominated by the eutectic pair, is unclear. Here, we unambiguously show the structure of choline chloride-malic acid (malicine) as a liquid, and also in solid and hydrated forms, using neutron total scattering on D/H isotope-substituted samples, and quasi-elastic neutron scattering (QENS). Data were refined using empirical potential structure refinement. We show evidence for a stoichiometric complex ion cluster in the disordered liquid, with strong choline-chloride bonding and a hydrogen bond donor (HBD) contribution. The 1:1 eutectic stoichiometry makes these ionic domains more well-defined, with less HBD clustering than seen previously for reline. There is minimal structural difference for the solidified material, demonstrating that this DES solidification is a glass transition rather than a first order phase change. QENS data support this by showing a gradual change in solvent dynamics rather than a step change. The DES structure is mostly retained upon hydration, with water acting both as a secondary smaller HBD at closer range to choline than malic acid, and forming transient wormlike aggregates. This new understanding of DES structure will aid understanding of the properties of these novel green solvents on the molecular length scale in chemical processes, as well as giving an insight into the apparent role of natural DESs in plant physiology.

Donor and recipient contribution to phenotypic traits and the expression of biomineralisation genes in the pearl oyster model Pinctada margaritifera

Grafting associates two distinct genotypes, each of which maintains its own genetic identity throughout the life of the grafted organism. Grafting technology is well documented in the plant kingdom, but much less so in animals. The pearl oyster, Pinctada margaritifera, produces valuable pearls as a result of the biomineralisation process of a mantle graft from a donor inserted together with a nucleus into the gonad of a recipient oyster. To explore the respective roles of donor and recipient in pearl formation, a uniform experimental graft was designed using donor and recipient oysters monitored for their growth traits. At the same time, phenotypic parameters corresponding to pearl size and quality traits were recorded. Phenotypic interaction analysis demonstrated: 1) a positive correlation between recipient shell biometric parameters and pearl size, 2) an individual donor effect on cultured pearl quality traits. Furthermore, the expressions of biomineralisation biomarkers encoding proteins in the aragonite or prismatic layer showed: 1) higher gene expression levels of aragonite-related genes in the large donor phenotype in the graft tissue, and 2) correlation of gene expression in the pearl sac tissue with pearl quality traits and recipient biometric parameters. These results emphasize that pearl size is mainly driven by the recipient and that pearl quality traits are mainly driven by the donor.

Contribution Limits and Transparency in a Campaign Finance Experiment

We experimentally compare electoral outcomes when donor contribution limits are varied. The effect of contribution limits is studied under three levels of transparency: one where donors' preferences and donations are unobserved by the candidate and public; one where they are observed by the candidate but not the public; and one where they are observed by all. We find that a combination of stricter contribution limits and full transparency is most successful at limiting donors' influence on policy choice. We also find that stricter contribution limits improve social welfare in some treatments. We further find that the partial and no anonymity settings lead to “centrist bias,” whereby implemented policies, on average, are more centrist than the candidate's preferences in most treatments.