True Progenitor Research Articles

Cranial volume and palate length of cats, Felis spp., under domestication, hybridization and in wild populations.

Reduced brain size, compared with wild individuals, is argued to be a key characteristic of domesticated mammal species, and often cited as a key component of a putative ‘domestication syndrome’. However, brain size comparisons are often based on old, inaccessible literature and in some cases drew comparisons between domestic animals and wild species that are no longer thought to represent the true progenitor species of the domestic species in question. Here we replicate studies on cranial volumes in domestic cats that were published in the 1960s and 1970s, comparing wildcats, domestic cats and their hybrids. Our data indicate that domestic cats indeed, have smaller cranial volumes (implying smaller brains) relative to both European wildcats (Felis silvestris) and the wild ancestors of domestic cats, the African wildcats (Felis lybica), verifying older results. We further found that hybrids of domestic cats and European wildcats have cranial volumes that cluster between those of the two parent species. Apart from replicating these studies, we also present new data on palate length in Felis cat skulls, showing that domestic cat palates are shorter than those of European wildcats but longer than those of African wildcats. Our data are relevant to current discussions of the causes and consequences of the ‘domestication syndrome’ in domesticated mammals.

The Renunciation of Robert E. Park: Myths about his Sociological Work

Three pernicious myths that have been perpetuated about Robert E. Park merit our present attention. These myths are important because they now foreclose almost any chance of him ever becoming recognized as the true progenitor of the interactionist school of thought or of latter-day sociologist from building on his work. The first myth, which lays the foundation for the other two, is that he was a social Darwinist. The second and third myths, which directly follow from the first one, are that Park concocted a racist and conservative sociology. An inquiry into his sociological works published over more than a quarter of a century, however, reveals that these myths are based more on fiction than fact. Although these myths are widely maintained among present-day sociologists, they appear to be driven more by prevailing ideology than supported by hard evidence (i.e. the full written record of what Park actually argued in his sociological publications). This confusion underscores the danger of advocacy research, an approach currently in vogue in the field of sociology.

Researchers Continue to Debate Adult Neurogenesis

Researchers Continue to Debate Adult Neurogenesis

Identification of Newly Committed Pancreatic Cells in the Adult Mouse Pancreas

Multipotent epithelial cells with high Aldehyde dehydrogenase activity have been previously reported to exist in the adult pancreas. However, whether they represent true progenitor cells remains controversial. In this study, we isolated and characterized cells with ALDH activity in the adult mouse or human pancreas during physiological conditions or injury. We found that cells with ALDH activity are abundant in the mouse pancreas during early postnatal growth, pregnancy, and in mouse models of pancreatitis and type 1 diabetes (T1D). Importantly, a similar population of cells is found abundantly in healthy children, or in patients with pancreatitis or T1D. We further demonstrate that cells with ALDH activity can commit to either endocrine or acinar lineages, and can be divided into four sub-populations based on CD90 and Ecadherin expression. Finally, our in vitro and in vivo studies show that the progeny of ALDH1+/CD90−/Ecad− cells residing in the adult mouse pancreas have the ability to initiate Pancreatic and duodenal homeobox (Pdx1) expression for the first time. In summary, we provide evidence for the existence of a sortable population of multipotent non-epithelial cells in the adult pancreas that can commit to the pancreatic lineage following proliferation and mesenchymal to epithelial transition (MET).

DISCOVERY OF VARIABILITY OF THE PROGENITOR OF SN 2011dh IN M 51 USING THE LARGE BINOCULAR TELESCOPE

We show that the candidate progenitor of the core-collapse SN 2011dh in M51 (8 Mpc away) was fading by 0.039 +- 0.006 mag/year during the three years prior to the supernova, and that this level of variability is moderately unusual for other similar stars in M 51. While there are uncertainties about whether the true progenitor was a blue companion to this candidate, the result illustrates that there are no technical challenges to obtaining fairly high precision light curves of supernova progenitors using ground based observations of nearby (<10 Mpc) galaxies with wide field cameras on 8m-class telescopes. While other sources of variability may dominate, it is even possible to reach into the range of evolution rates required by the quasi-static evolution of the stellar envelope. For M 81, where we have many more epochs and a slightly longer time baseline, our formal 3 sigma sensitivity to slow changes is presently 3 millimag/year for a M_V ~= -8 mag star. In short, there is no observational barrier to determining whether the variability properties of stars in their last phases of evolution (post Carbon ignition) are different from earlier phases.

Ischemia/Reperfusion Injury, Its Mechanisms, and Prevention

Since the beginning of transplantation era, ischemia/reperfusion injury (IRI) has remained one of the most serious pitfalls of the procedure. Although thousands of scientific studies and analyses have been published, and mechanisms of the injury recognized and described, the most serious step forward to avoid the IRI was Geoffrey Collins' and Folkert Belzer's invention of two different intracellular-type solutions in 1960s, which allowed for safe renal preservation exceeding 24 hours. Since then, no such important improvement took place and prevention of IRI remains a holy grail of transplantation, especially in thoracic and sub-optimal abdominal organs (fatty livers, older donor kidneys). In this issue we present two studies examining various modalities to reduce both cold and warm ischemia. W. Li et al. showed significant improvement in posttransplantation liver function tests, histology, and reduction of apoptosis with administration of sodium nitrite either to preservation solution or directly to the recipient animal. What is more important is that protection was more evident with more pronounced injury, when liver cold ischemia time was extended to 18–24 hours. Although NO is believed to render protection only in specific concentrations, the authors have shown a dose-dependent effect in a 25–250 uM concentration range. In this edition also, M. G. W. van den Heuvel et al. present use of statins in a human model of approximately one hour warm ischemia and reperfusion during breast reconstruction with free cutaneous flap. Although numerous authors postulate usefulness of statins in attenuation of ischemia/reperfusion injury (IRI) [1, 2], employing dozens of pathways and mechanisms in rendering protection, in this study statins did not show any benefit and rather deteriorated the results and increased risk of complications in skin flap warm ischemia and transposition. Some agents can be administered in a gaseous form and A. Siriussawakul et al. give a nice overview of potential applications and proposed mechanisms of action of inhaled nitric oxide, carbon monoxide, and hydrogen sulfide in prevention of IRI and inflammation. Liver is known to tolerate 12 hours of cold ischemia relatively well. However, exceeding preservation beyond this time leads to significant deterioration of both short and long term results of transplantation. This decline is mostly due to biliary pathology, as biliary tree is the most ischemia susceptible tissue of the liver. R. Cursio and J. Gugenheim give a nice overview of biliary complications after liver transplantation. They extensively discuss pathomechanism of ischemic type biliary lesions and the role of cold and warm ischemia as well as intrahepatic cholestasis, bile salts, and immune-dependent events in development of this phenomenon. Posttransplant acute renal failure is mainly caused by ischemia and reperfusion. Although primary damage occurs mainly to tubular cells, microvasculature is also affected, especially with prolonged warm ischemia. This becomes clinically more sound with more and more organs retrieved after cardiac death. Patschan et al. discuss features and mechanism of endothelial cells' injury in renal IRI and potential therapeutic application of endothelial progenitor cells. With the focus of contemporary medicine on regenerative technologies this is definitely a “sexy” topic in IRI, regardless of wether peripheral blood-retrieved endothelial outgrowth cells are true progenitor cells or not. What is more important, several authors mention antifibrogenic properties of such therapy, making it even more attractive in the field of renal transplantation. A key player involved in inflammation, cellular apoptosis and survival in a transplanted organ is a pathway of mitogen activated protein kinases (MAPKs). Despite its essential role in recovery from ischemia, and some new inhibiting agents with potential therapeutic application in the pipeline, this pathway is rather poorly recognized by transplant physicians. We decided to publish a review by G. Vassalli et al., who give a concise description of MAPK pathway in ischemia/reperfusion injury and ischemic preconditioning of the heart. Bases of this knowledge are critical not only to surgeons involved in heart or other organ transplantation, but equally to any other physician treating patients for coronary disease or myocardial infarction. Maciej Kosieradzki Johann Pratschke Jerzy Kupiec-Weglinski Wojciech Rowinski

Myeloid Angiogenic Cells Act as Alternative M2 Macrophages and Modulate Angiogenesis through Interleukin-8

Endothelial progenitor cells (EPCs) promote angiogenesis, and clinical trials have shown such cell therapy to be feasible for treating ischemic disease. However, clinical outcomes have been contradictory owing to the diverse range of EPC types used. We recently characterized two EPC subtypes, and identified outgrowth endothelial cells as the only EPC type with true progenitor and endothelial characteristics. By contrast, myeloid angiogenic cells (MACs) were shown to be monocytic cells without endothelial characteristics despite being widely described as "EPCs." In the current study we demonstrated that although MACs do not become endothelial cells or directly incorporate into a microvascular network, they can significantly induce endothelial tube formation in vitro and vascular repair in vivo. MAC-derived interleukin-8 (IL-8) was identified as a key paracrine factor, and blockade of IL-8 but not vascular endothelial growth factor (VEGF) prevented MAC-induced angiogenesis. Extracellular IL-8 transactivates VEGFR2 and induces phosphorylation of extracellular signal-regulated kinases. Further transcriptomic and immunophenotypic analysis indicates that MACs represent alternative activated M2 macrophages. Our findings demonstrate an unequivocal role for MACs in angiogenesis, which is linked to paracrine release of cytokines such as IL-8. We also show, for the first time, the true identity of these cells as alternative M2 macrophages with proangiogenic, antiinflammatory and pro-tissue-repair properties.

Elizabeth Bowen: new critical perspectives

Bowen has in more recent times been recognised as being as radically important to our understanding of twentieth-century literature as Samuel Beckett and she is now considered among the most highly significant writers of the twentieth century. This collection of essays is intended to broaden the critical framework of Bowen scholarship and to extend Bowen criticism by more clearly mapping her work's position in relation to contemporary critical concerns and its location in relation to twentieth-century literature generally. Combining close textual analysis with theoretically informed readings, in this groundbreaking collection, this group of leading international scholars explores how Bowen's disruptive and deeply unconventional narratives encourage us to read her as one of the most innovative writers of modern fiction, a true progenitor of modernism.The original and freshly illuminating essays chosen for Elizabeth Bowen: New Critical Perspectives cite and expound the dynamics of Bowen's fiction's originality and value. While some essays explore her fictional narratives' Beckettian affinities, her narratives' relation to the Gothic, and the multiple ways her work challenges the norms and boundaries of realism, others examine their representation of Sapphic relations, the unexpected ways her work estranges the conventionally conceived dialogic relation of reader and narrative, and the complex relation of the aesthetic and the ethical in her narratives.Others explore her fiction's unexpected connections to a range of specific historical issues of major consequence during the early and mid-twentieth century including the interrelated questions of sexuality, gender, race, ethnicity, nation and war. These readings of Bowen's work will have widespread appeal and will be of special interest to scholars and students of twentieth-century English and Anglo-Irish literature, post-colonial literature, writers of the thirties and forties, twentieth-century women's fiction, reading theory, literary realism and literary modernism as well as to the educated general reader.

280 ISOLATION, PRESERVATION, AND CHARACTERIZATION OF EQUINE UMBILICAL CORD BLOOD STEM CELLS

The isolation, preservation, and identification of hematopoietic and mesenchymal stem cells from fresh umbilical cord blood (UCB) has been extensively reported in humans. Although both types of stem cells may be of therapeutic interest in horses, data on equine UCB cells are scarce. In the present study, two separation methods to isolate stem and progenitor cells from equine UCB and two cryoprotectant solutions for their subsequent freezing were compared. Characterization of the isolated cells was evaluated flow cytometrically, based on the presence of the cytosolic enzyme aldehyde dehydrogenase (ALDH), which has been shown to be highly expressed in primitive hematopoietic cells in a number of species. Cord blood was collected from 15 foals immediately after birth. While the placenta was still in utero, the umbilical cord was clamped and disinfected. A sterile blood bag collection system containing citrate-phosphate-dextrose-adenine anticoagulant was used to collect the UCB by gravity. The UCB units were stored at 4�C and processed within 36 h. Percoll density gradient separation and rouleaux formation induced by hydroxyethyl starch (HES) were tested in parallel on equal volumes of each UCB unit. The enriched progenitor cell fraction was cryopreserved at 10 � 106 nucleated cells mL–1 using two cryoprotectant solutions based on plasma or RPMI 1640, and both containing 10% DMSO and DNase I (20 IU mL–1). Before and after thawing, cells were labeled using a fluorescent ALDH substrate (Aldefluor�, StemCell Technologies SARL, Grenoble, France) including a negative control. Cell viability was simultaneously evaluated by means of exclusion of propidium iodide. Cryopreservation was performed using a programmable freezer (–1�C/min–1 until –70�C, then –10�C/min–1 until –140�C) prior to storage in liquid nitrogen. Results were analyzed statistically with a nonparametric Mann-Whitney test. The concentration of the isolated UCB cells ranged from 0.3 to 4 � 106 cells mL–1 for Percoll and from 0.4 to 7.3 � 106 cells mL–1 for HES. The average viability before and after freezing was 94% and 93% for Percoll-, and 93% and 94% for HES-separated cells, respectively. No significant differences in concentration or in viability were observed between both isolation procedures and both cryoprotectant solutions. Before freezing, the proportion of Aldefluor�-positive cells after Percoll and HES isolation ranged between 0.5 and 38% and between 1 and 60.5%, respectively. No significant differences were found. In conclusion, the percentage of ALDH-positive cells as determined by flow cytometry was highly variable between foals, but was independent of the isolation procedures used. Whether the isolated cells represent true progenitor cells remains to be confirmed. Ongoing, flow cytometrical experiments showed that the isolated cells are CD29+ and CD44+, which may be indicative for their mesenchymal origin.

805. Efficient Transduction of Human Cord Blood and Adult Peripheral Blood CD34+ Progenitors with HSV-1 Derived Amplicon Vectors

Top of pageAbstract Amplicons are promising helper-dependent HSV-1-derived vectors that allow the transfer and expression of large DNA fragments into dividing and quiescent cells. Their capacity to transduce human hematopoietic progenitors has been poorly evaluated so far. We here describe the use of an improved HSV-1 Amplicon Vector to genetically modify human CD34+ blood progenitor cells. This improved packaging system allows for the production of high titers of amplicon vectors with low levels of fully defective, non pathogenic helper contamination. The EGFP-HSV-1 Amplicon vector was used to infect immuno-selected human CD34+ progenitor cells obtained from umbilical cord or mobilized peripheral blood cell samples. Without pre-stimulation of CD34+ cells, the transduction efficiency ranged from 1 to 10%, as determined by FACS analysis. In culture conditions that stimulate CD34+ blood progenitor cells to divide while maintaining cell pluripotency, and in the presence of fibronectin, more than 40% of CD34+ cells were transduced at a MOI of 50. Mature and immature phenotypically defined subsets of CD34+ cells were transduced. The transduced cells were viable and could be sorted by flow cytometry. GFP+ cells were able to produce colonies in clonogenic cultures and to engraft NOD-SCID mice after sub-lethal irradiation, suggesting that true progenitor cells had been targeted by the vector. It makes from HSV derived vectors a promissing tool for gene transfer in hematopoietic stem cells.

Hematopoietic, vascular and cardiac fates of bone marrow-derived stem cells.

Bone marrow contains many cell types, including stroma, vascular cells, adipocytes, osteoblasts and osteoclasts, as well as mesenchymal stem cells and hematopoietic stem cells. It was previously thought that cells within bone marrow solely functioned to regenerate cells within the marrow, as well as all circulating hematopoietic cells in peripheral blood. Recent reports, however, suggest that marrow-derived cells can also regenerate other cell types, including cardiac muscle, liver cell types, neuronal and non-neuronal cell types of the brain, as well as endothelial cells and osteoblasts. These multiple cell types could have originated from either of the stem cell populations within bone marrow or potentially other precursors. Therefore, it is not entirely clear whether each of these distinct cell lineages has a true progenitor within marrow or whether the marrow contains a multipotent population of cells that has been set aside during embryogenesis for postnatal repair and remodeling of a variety of tissues. It is clear, however, that directing the fate of bone marrow-derived progenitors (ie toward hematopoietic, vascular or cardiac cell fates) can only be accomplished if the phenotype of the stem cells is defined, and their homing and differentiation programs are elucidated. Much work is focused on these issues, wherein lie the key to harnessing the potential of adult stem cells for autologous cell and gene therapy.

Isozyme Diversity in Bambara Groundnut

Bambara groundnut [Vigna subterranea (L.) Verde.] is an important crop in many countries of tropical Africa. Compared with other leguminous crops, little is known about the organization of its genetic diversity. Our goal was to investigate its population structure and the partitioning of genetic diversity between domesticated and wild accessions. Seventy‐nine accessions of domesticated and 21 wild Bambara groundnut populations were evaluated for genetic diversity at 41 isozyme loci, representing 23 enzyme systems. Domesticated accessions were characterized by very low genetic diversity (Ht = 0.052) with only 7 polymorphic loci. Wild populations were characterized by higher genetic diversity (Ht = 0.087), with 14 polymorphic. This suggests a marked bottleneck between wild and domesticated forms. Intrapopulation diversity was comparatively high (Hs = 0.033 for domesticated and Hs = 0.025 for wild populations) despite the near absence of heterozygous individuals, which suggests a predominantly selfing mode of pollination in both wild and domesticated Bambara groundnut High genetic identity between wild and domesticated forms suggests that wild Bambara groundnut is the true progenitor of domesticated Bambara groundnut. Both morphological and isozyme data show a gradient between true wild and domesticated Bambara groundnut through weedy populations. The improved understanding of the organization of genetic diversity of Bambara groundnut provided by our data will allow a better conservation of its genetic resources.

Common Rights of Mankind in Gentili, Grotius and Suárez

Students of the concept of erga omnes trace its antecedents to the early recognition of the right of humanitarian intervention, which they often attribute to Grotius. Professor Hersch Lauterpacht asserted that Grotius’s writings contained “the first authoritative statement of the principle of humanitarian intervention— the principle that exclusiveness of domestic jurisdiction stops when outrage upon humanity begins.” However, some of the other principal works on international law before the Peace of Westphalia (1648) reveal that the concept of community interests, and the modern right of humanitarian intervention it spawned, is pre-Grotian, that it appeared in the writings of Suárez and figured prominently in those of its true progenitor, the earlier Gentili.

A technical bias: Differences in cooling rates prevent ampoules from being a reliable index of stem cell cryopreservation in large volumes

Ampoule tests are commonly used as an index of the cryopreservation efficiency of marrow stem cells in bags. We have studied the recovery of hematopoietic progenitor cells (CFU-GM, BFUe) in 52 ampoules and compared it to the recovery in 83 standard bags. Our data showed significantly deficient CFU-GM and BFUe recoveries (respectively 47 ± 31% and 31 ± 30%) in ampoules when compared to bags (respectively 72 ± 22% and 64 ± 19%; P < 0.001). Moreover, a good progenitor cell recovery (⩾50%) was observed in only 46% of frozen ampoules versus 100% observed in frozen bags ( P < 0.05). We were able to relate this nonoptimal recovery to an excessively rapid freezing rate of −9 °C/ min following the release of fusion heat which occurred in ampoules, while the freezing rate was constantly maintained at −2 °C/min in the corresponding bags. We therefore conclude that the cooling conditions have to be carefully controlled to ensure that the bags and ampoules are both cooled under the same conditions. Otherwise, ampoules would not be a realiable index of the true progenitor cells' cryopreservation efficiency in bags.