bluuebunny/crossref_metadata_2025 huggingface dataset:
Ion Mobility Spectrometry of Gas-Phase Ions from Laser Ablation of Solids in Air at Ambient Pressure
Authors: Eiceman G. A. , Young D. , Schmidt H. , Rodriguez J. E. , Baumbach J. I. , Vautz W. , Lake D. A. , Johnston M. V.
Published: October 2007

A mobility spectrometer was used to characterize gas-phase ions produced from laser ablation of solids in air at 100 °C and at ambient pressure with a beam focused to a diameter of <0.2 mm at energy of 6 mJ/pulse and wavelength of 266 nm. Metals, organic polymers, glass, graphite, and boron nitride exhibited characteristic mobility spectra with peaks at drift times between 8.75 and 12.5 ms (reduced mobility values of 2.19 to 1.53 cm2/Vs). Ion intensities increased initially and then decreased with repeated laser shots through drilling of the solid, and persistence of signal was proportional to hardness. A single comparatively narrow peak for negative ions was observed in mobility spectra for all materials and this was mass-identified as O2−. These ions were formed in air from reactions of oxygen with electrons emitted from the ablation step. Positive ions ablated directly from the solid were masked in ion mobility spectrometry/mass spectrometry (IMS/MS) studies by ionization of moisture and impurities. Positive ions from solids were seen only in the IMS analyzer at elevated temperature and low moisture. Under such conditions, materials were classified from mobility spectra alone with principal component analysis.
Prion Protein α-to-β Transition Monitored by Time-Resolved Fourier Transform Infrared Spectroscopy
Authors: Ollesch Julian , Künnemann Eva , Glockshuber Rudi , Gerwert Klaus
Published: October 2007

The conformational change of the recombinant, murine prion protein (PrP) from an α-helical to a β-sheet enriched state was monitored by time-resolved Fourier transform infrared (FT-IR) spectroscopy. The α-to-β transition is induced by reduction of the single disulfide bond in PrP. This transition is believed to generate the scrapie form PrPSc, the supposed infectious agent of transmissible spongiform encephalopathies. We followed the kinetics of this conformational change using a novel method for amide I band analysis of the infrared (IR) spectra. The amide I analysis provides the secondary structure. The amide I decomposition was calibrated with the three dimensional structure of cellular PrP solved by nuclear magnetic resonance (NMR). The novel secondary structure analysis provides a root mean squared deviation (RMSD) of only 3% as compared to the NMR structure. Reduction of α-helical PrP caused the transient accumulation of a partially unfolded intermediate, followed by formation of a state with higher β-sheet than α-helical structure contents. The novel approach allows us to now determine the secondary structure of the β-sheet conformation. This was not determined by either NMR or X-ray. The experiments were performed in a double-sealed security cuvette developed for IR analysis of potentially infectious PrP samples outside the biosafety laboratory.
Measurement of Nonlinear Absorption Coefficients of Organic Materials by Mode-Mismatched Z-scan Thermal Lensing Technique
Authors: Guerra M. , Taouri A. , Marcano A. O. , Cabrera H. , Sylla M.
Published: October 2007

We evaluate a new pump–probe mode-mismatched thermal lens (TL) scheme for the measurement of nonlinear absorption in nitrobenzene, benzene, and chloroform. In this new scheme the pump beam is focused in the presence of a collimated probe beam. Values of the nonlinear absorption coefficients of the materials studied for the wavelength of 532 nm are reported, and we compare the proposed technique with the well-known open Z-scan method.
Deep Subsurface Raman Spectroscopy of Turbid Media by a Defocused Collection System
Authors: Eliasson C. , Claybourn M. , Matousek P.
Published: October 2007

A simple procedure for the recovery of deep subsurface Raman spectra in stratified turbid samples by defocusing a conventional Raman instrument is presented. The method is based on effects present with spatially offset Raman spectroscopy (SORS) and, although not as efficient as the standard SORS approach, it permits a simple way of recovering subsurface Raman spectra from less challenging samples. Demonstration of the effect is performed using a standard SORS device and a commercial Raman instrument on the noninvasive measurement of paracetamol tablets held within a nontransparent white plastic bottle.
Renal Dysfunction Is a Confounder for Plasma Natriuretic Peptides in Detecting Heart Dysfunction in Uremic and Idiopathic Dilated Cardiomyopathies
Authors: Codognotto Marta , Piccoli Antonio , Zaninotto Martina , Mion Monica , Plebani Mario , Vertolli Ugo , Tona Francesco , Ruzza Luisa , Barchita Agata , Boffa Giovanni M
Published: October 2007

Background: The diagnostic value of natriuretic peptides in uremic cardiomyopathy has not been defined, nor has the effect of a hemodialysis (HD) session on peptides.

Methods: We performed an observational study of 100 white adult outpatients in New York Heart Association class I–II, with neither diabetes nor ischemic heart disease, 50 of whom had idiopathic dilated cardiomyopathy (DCM) and 50 of whom had uremic cardiomyopathy and were undergoing HD. We measured plasma N-terminal proB-type natriuretic peptide (NT-proBNP), BNP, and atrial natriuretic peptide (ANP) both before and after a dialysis session. Doppler echocardiograms were evaluated. We performed multiple regression analysis on the logarithm of peptide concentrations using clinical, laboratory, and echocardio-Doppler data as explanatory variables.

Results: Mean peptide concentrations were higher in the HD group, with an HD:DCM ratio of 25 for NT-proBNP and 5 for BNP and ANP. Peptides were correlated with each other (r > 0.85). After HD, NT-proBNP significantly increased by 14%, BNP decreased by 17%, and ANP decreased by 56%. Predialysis concentrations correlated with postdialysis values (r > 0.85). A multiple regression equation significantly fitted the observed peptide concentrations, both pre- and postdialysis, using the same set of 4 variables: disease group (DCM or HD), diastolic pattern, left atrial volume, and body mass index.

Conclusions: Renal dysfunction was a confounder for natriuretic peptides, which were present in higher concentrations in the uremic patients with milder cardiac dysfunction than in those with idiopathic DCM without renal dysfunction. Left diastolic function pattern and atrial volume were cardiac determinants of peptide concentrations in DCM and HD.
The behaviour of organic solvents containing C5-BTBP and CyMe4-BTBP at low irradiation doses
Authors: Retegan Teodora , Ekberg Christian , Englund Sofie , Fermvik Anna , Foreman M. R. S. , Skarnemark Gunnar
Published: October 2007

Low doses of gamma radiation were given to four different solvents containing C5-BTBP and CyMe4-BTBP, each molecule dissolved both in cyclohexanone and hexanol. Four corresponding solvents were kept unirradiated and used as references for the extraction experiments. Multiple samples were taken from both the irradiated solutions and the reference solutions at certain time intervals. The samples were used in extraction experiments with the radionuclides 241Am and 152Eu. The protection against radiolysis of the extracting molecules by the diluent used for dissolution without adding a scavenger molecule was checked. The interplay between the diluent and the side group of the extracting molecule for protection against radiolysis was also studied by keeping the same type of core molecule for binding to the metal ions and varying the diluent and side group.

The results were unexpected. The presence of a cyclic molecule as both a side group or diluent seems to keep the extraction of europium almost unaffected by radiolysis, while americium behaves differently from solvent to solvent. The diluent alone does not protect the extracting molecule. In some of the studied systems there is a distinct change in the extraction behaviour of Am between the irradiated and reference solutions, an effect that is however only present at the beginning of the experimental series. At later times the difference in distribution ratios between the irradiated and reference solution is constant. This phenomenon is found only when the side group and diluent are structurally dissimilar.
Study of RuO4 decomposition in dry and moist air
Authors: Mun Christian , Cantrel L. , Madic Charles
Published: October 2007

During a hypothetical severe nuclear accident on a pressurized water reactor (PWR), it is of primary importance to assess potential radionuclide release into the environment, and thus to better understand the volatile ruthenium tetroxide stability, in the containment building, due to its high radiotoxicity. The stability of RuO4(g) in dry and moist air, under conditions representative of a PWR containment building, is investigated. RuO4 decomposition occurs in bulk gas phase, without any specific affinity with surfaces. The kinetic rate law of RuO4 reduction is found to be dependent on the presence of steam. The humidity seems to play a catalytic role, as well as the presence of ruthenium dioxide deposits. The temperature is also a key parameter. In the presence of steam, the half-life times of RuO[4] are found to be respectively of 5 h and 9 h at 90 °C and 40 °C. A chemical reaction scheme consistent with the experimental observations is proposed.
Japan, the Active State?: Security Policy after 9/11
Authors: Arase David
Published: October 2007

An alignment of international structure, domestic institutions, and security norms after 9/11 permits Japan to change in unprecedented ways. New external threats and U.S. encouragement are speeding the pace, but caution is advised.
The North Korean Nuclear Crisis and U.S. Strategy in Northeast Asia
Authors: Rozman Gilbert
Published: October 2007

The nuclear crisis tested the U.S. in four distinct periods from 2002 to 2007, as slowly its strategy shifted toward multilateralism. After failing to rally any state but Japan to its side, the U.S. approved the Joint Agreement by working more closely with China. With Phase 1 finishing, Phase 2 puts a premium on multilateralism for which the U.S. is unprepared.
My Dual Career
Authors: Pekar Harvey L.
Published: October 2007

Why did the author of American Splendor comics spend 37 years clerking at a VA hospital—and fret over retiring? The vicissitudes of life and work.
Conceptualizing translation competence
Authors: Lesznyák Márta
Published: October 2007

The aim of the present article is to give an overview of the most important approaches to translation competence. As the term ‘competence’ is used in a somewhat arbitrary way in translation studies, psychological approaches to competence are reviewed first. Then some influential translation competence models are presented and analyzed. Translation competence models are classified into three categories based on Pym (2003). The outlined translation competence models are also related to the psychological concepts of competence described at the beginning of the study. Finally, recurrent issues related to translation competence are identified and discussed briefly. These issues involve the relationship between language competence and translation competence; the existence of a separate transfer component of competence, the status of natural translation and the differences between L1→L2 and L2→L1 translation. It is concluded that none of the models of translation competence is inherently better than the others. It is always the purpose of a given piece of research or project that should determine the type of competence model to be adopted.
Medida da pressão arterial e a produção científica de enfermeiros brasileiros
Authors: Arcuri Edna Apparecida Moura , Araújo Thelma Leite de , Veiga Eugênia Veludo , Oliveira Sonia Maria Junqueira Vasconcellos de , Lamas José Luiz Tatagiba , Santos Jair Lício Ferreira
Published: October 2007

No número anterior a este periódico, os autores apresentaram matéria comemorativa sobre a descoberta dos Sons de Korotkoff, em 1905. Relataram os determinantes históricos que resgatam o importante papel da Escola de Enfermagem da Universidade de São Paulo-EEUSP, no desenvolvimento da mais antiga linha de pesquisa de pressão arterial na enfermagem brasileira: "Influência da Largura do Manguito na Medida da Pressão Arterial". Neste artigo é apresentada a produção científica decorrente dos estudos realizados pelos doutores formados na EEUSP, enfatizando-se a trajetória de cada pesquisador em seus respectivos núcleos e laboratórios, com o objetivo de oferecer alguns indicadores que permitem avaliar, qualitativa-quantitativamente, o impacto das pesquisas realizadas e a caracterização do conhecimento na área.
Lysophosphatidic Acid Protects Mesenchymal Stem Cells Against Hypoxia and Serum Deprivation-Induced Apoptosis
Authors: Chen Jinghai , Baydoun Anwar R. , Xu Ruixia , Deng Linzi , Liu Xuebin , Zhu Weiquan , Shi Linhui , Cong Xiangfeng , Hu Shengshou , Chen Xi
Published: October 2007

Bone marrow-derived mesenchymal stem cells (MSCs) have shown great promise for cardiac repair. However, poor viability of transplanted MSCs within the ischemic heart has limited their therapeutic potential. Our previous studies have documented that hypoxia and serum deprivation (hypoxia/SD), induced MSCs apoptosis through the mitochondrial apoptotic pathway. Since serum lysophosphatidic acid (LPA) levels are known to be significantly elevated after acute myocardial infarction and that LPA enhanced survival of other cell systems, we embarked on determining whether LPA protects MSCs against hypoxia/SD-induced apoptosis. We have also investigated the potential mechanism(s) that may mediate such actions of LPA. All experiments were carried out on rat bone marrow MSCs. Apoptosis was induced by exposure of cells to hypoxia/SD in a sealed GENbox hypoxic chamber. Effects of LPA were investigated in the absence and presence of inhibitors that target either Giproteins, the mitogen activated protein kinases ERK1/2, or phosphoinositide 3-kinase (PI3K). The data obtained showed that hypoxia/SD-induced apoptosis was significantly attenuated by LPA through Gi-coupled LPA1 receptors linked to the downstream ERK1/2 and PI3K/Akt signaling pathways that function in parallel. Additional studies have demonstrated that hypoxia/SD-induced activation of mitochondrial dysfunction was virtually abolished by LPA treatment and that inhibition of the LPA1 receptor, Gi proteins, the PI3K/Akt pathway, or ERKs effectively reversed this protective action of LPA. Taken together, our findings indicate that LPA is a novel, potent survival factor for MSCs and this may prove to be of considerable therapeutic significance in terms of exploiting MSC-based therapy in the infracted myocardium.

Disclosure of potential conflicts of interest is found at the end of this article.
Novel Effectors of Directed and Ngn3-Mediated Differentiation of Mouse Embryonic Stem Cells into Endocrine Pancreas Progenitors
Authors: Serafimidis Ioannis , Rakatzi Irini , Episkopou Vasso , Gouti Mina , Gavalas Anthony
Published: October 2007

The delineation of regulatory networks involved in early endocrine pancreas specification will play a crucial role in directing the differentiation of embryonic stem cells toward the mature phenotype of β cells for cell therapy of type 1 diabetes. The transcription factor Ngn3 is required for the specification of the endocrine lineage, but its direct targets and the scope of biological processes it regulates remain elusive. We show that stepwise differentiation of embryonic stem cells using successive in vivo patterning signals can lead to simultaneous induction of Ptf1a and Pdx1 expression. In this cellular context, Ngn3 induction results in upregulation of its known direct target genes within 12 hours. Microarray gene expression profiling at distinct time points following Ngn3 induction suggested novel and diverse roles of Ngn3 in pancreas endocrine cell specification. Induction of Ngn3 expression results in regulation of the Wnt, integrin, Notch, and transforming growth factor β signaling pathways and changes in biological processes affecting cell motility, adhesion, the cytoskeleton, the extracellular matrix, and gene expression. Furthermore, the combination of in vivo patterning signals and inducible Ngn3 expression enhances ESC differentiation toward the pancreas endocrine lineage. This is shown by strong upregulation of endocrine lineage terminal differentiation markers and strong expression of the hormones glucagon, somatostatin, and insulin. Importantly, all insulin+ cells are also C-peptide+, and glucose-dependent insulin release was 10-fold higher than basal levels. These data suggest that bona fide pancreas endocrine cells have been generated and that timely induction of Ngn3 expression can play a decisive role in directing ESC differentiation toward the endocrine lineage.

Disclosure of potential conflicts of interest is found at the end of this article.
Mesenchymal Stem Cells Cooperate with Bone Marrow Cells in Therapy of Diabetes
Authors: Urbán Veronika S. , Kiss Judit , Kovács János , Gócza Elen , Vas Virág , Monostori Ėva , Uher Ferenc
Published: October 2007

Several recent studies have suggested that the adult bone marrow harbors cells that can influence β-cell regeneration in diabetic animals. Other reports, however, have contradicted these findings. To address this issue, we used an animal model of type 1 diabetes in which the disease was induced with streptozotocin in mice. Freshly prepared sex-mismatched bone marrow cells (BMCs) and syngeneic or allogeneic mesenchymal stem cells (MSCs) were concomitantly administrated into sublethally irradiated diabetic mice. Blood glucose and serum insulin concentrations rapidly returned to normal levels, accompanied by efficient tissue regeneration after a single injection of a mixture of 106 BMCs per 105 MSCs. Neither BMC nor MSC transplantation was effective alone. Successful treatment of diabetic animals was not due to the reconstitution of the damaged islet cells from the transplant, since no donor-derived β-cells were found in the recovered animals, indicating a graft-initiated endogenous repair process. Moreover, MSC injection caused the disappearance of β-cell-specific T lymphocytes from diabetic pancreas. Therefore, we suggest that two aspects of this successful treatment regimen operate in parallel and synergistically in our model. First, BMCs and MSCs induce the regeneration of recipient-derived pancreatic insulin-secreting cells. Second, MSCs inhibit T-cell-mediated immune responses against newly formed β-cells, which, in turn, are able to survive in this altered immunological milieu. Thus, the application of this therapy in human patients suffering from diabetes and/or other tissue destructive autoimmune diseases may be feasible.

Disclosure of potential conflicts of interest is found at the end of this article.
Multipotent Stem Cells from Umbilical Cord: Cord Is Richer than Blood!
Authors: Secco Mariane , Zucconi Eder , Vieira Natassia M. , Fogaça Luciana L.Q. , Cerqueira Antonia , Carvalho Maria Denise F. , Jazedje Tatiana , Okamoto Oswaldo K. , Muotri Alysson R. , Zatz Mayana
Published: October 2007

The identification of mesenchymal stem cell (MSC) sources that are easily obtainable is of utmost importance. Several studies have shown that MSCs could be isolated from umbilical cord (UC) units. However, the presence of MSCs in umbilical cord blood (UCB) is controversial. A possible explanation for the low efficiency of MSCs from UCB is the use of different culture conditions by independent studies. Here, we compared the efficiency in obtaining MSCs from unrelated paired UCB and UC samples harvested from the same donors. Samples were processed simultaneously, under the same culture conditions. Although MSCs from blood were obtained from only 1 of the 10 samples, we were able to isolate large amounts of multipotent MSCs from all UC samples, which were able to originate different cell lineages. Since the routine procedure in UC banks has been to store the blood and discard other tissues, such as the cord and/or placenta, we believe our results are of immediate clinical value. Furthermore, the possibility of originating different cell lines from the UC of neonates born with genetic defects may provide new cellular research models for understanding human malformations and genetic disorders, as well as the possibility of testing the effects of different therapeutic drugs.

Disclosure of potential conflicts of interest is found at the end of this article.
Oct-4 Is Critical for Survival/Antiapoptosis of Murine Embryonic Stem Cells Subjected to Stress: Effects Associated with Stat3/Survivin
Authors: Guo Ying , Mantel Charlie , Hromas Robert A. , Broxmeyer Hal E.
Published: October 2007

Understanding survival/antiapoptosis of murine embryonic stem (ES) cells may enhance their clinical potential. We hypothesized that Oct-4 might be involved in survival of undifferentiated ES cells under stress. The Oct-4 tetracycline conditional knockout cell line ZHBtc4 was used to test this possibility, and apoptosis was induced by either etoposide, heat shock, or UV exposure. Apoptosis in Oct-4 knocked-down ES cells was significantly increased in response to all stress situations compared with parental cells. Oct-4 knockdown was not associated with changes in morphology or expression of Nanog, SSEA-1, KLF-4, or Sox2 within the time frame and culture conditions used, suggesting that enhanced sensitivity of these cells to apoptosis was not due to an overtly differentiated state of the cells. To address potential intracellular mediators, we focused on the inhibitor of apoptosis proteins family member Survivin, an antiapoptosis protein. The Survivin promoter was transfected into ES cells after knockdown of Oct-4. Survivin promoter activity was dramatically decreased in the Oct-4 knockdown cells. Western blots substantiated that Oct-4 knockdown ES cells had decreased Survivin protein expression. Since the Survivin promoter does not have binding sites for Oct-4, this suggested an indirect effect of Oct-4 on expression of Survivin. Leukemia inhibitory factor-induced signal transducer and activator of transcription-3 (STAT3) is responsible for ES cell survival, and STAT3 regulates Survivin expression in breast cancer cells. Western blot analysis showed that downregulated Oct-4 was associated with decreased phosphorylation of STAT3. Our results suggest that Oct-4 is essential for antiapoptosis of ES cells in response to stress, effects that may be mediated through the STAT3/Survivin pathway.

Disclosure of potential conflicts of interest is found at the end of this article.
Human Mesenchymal Stem Cells Inhibit Neutrophil Apoptosis: A Model for Neutrophil Preservation in the Bone Marrow Niche
Authors: Raffaghello Lizzia , Bianchi Giordano , Bertolotto Maria , Montecucco Fabrizio , Busca Alessandro , Dallegri Franco , Ottonello Luciano , Pistoia Vito
Published: October 2007

Mesenchymal stem cells (MSC) establish close interactions with bone marrow sinusoids in a putative perivascular niche. These vessels contain a large storage pool of mature nonproliferating neutrophils. Here, we have investigated the effects of human bone marrow MSC on neutrophil survival and effector functions. MSC from healthy donors, at very low MSC:neutrophil ratios (up to 1:500), significantly inhibited apoptosis of resting and interleukin (IL)-8-activated neutrophils and dampened N-formyl-l-methionin-l-leucyl-l-phenylalanine (f-MLP)-induced respiratory burst. The antiapoptotic activity of MSC did not require cell-to-cell contact, as shown by transwell experiments. Antibody neutralization experiments demonstrated that the key MSC-derived soluble factor responsible for neutrophil protection from apoptosis was IL-6, which signaled by activating STAT-3 transcription factor. Furthermore, IL-6 expression was detected in MSC by real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Finally, recombinant IL-6 was found to protect neutrophils from apoptosis in a dose-dependent manner. MSC had no effect on neutrophil phagocytosis, expression of adhesion molecules, and chemotaxis in response to IL-8, f-MLP, or C5a. These results support the following conclusions: (a) in the bone marrow niche, MSC likely protect neutrophils of the storage pool from apoptosis, preserving their effector functions and preventing the excessive or inappropriate activation of the oxidative metabolism, and (b) a novel mechanism whereby the inflammatory potential of activated neutrophils is harnessed by inhibition of apoptosis and reactive oxygen species production without impairing phagocytosis and chemotaxis has been identified.

Disclosure of potential conflicts of interest is found at the end of this article.
Circulating Bone Marrow-Derived Osteoblast Progenitor Cells Are Recruited to the Bone-Forming Site by the CXCR4/Stromal Cell-Derived Factor-1 Pathway
Authors: Otsuru Satoru , Tamai Katsuto , Yamazaki Takehiko , Yoshikawa Hideki , Kaneda Yasufumi
Published: October 2007

Previous studies demonstrated the existence of osteoblastic cells in circulating blood. Recently, we reported that osteoblast progenitor cells (OPCs) in circulation originated from bone marrow and contributed to the formation of ectopic bone induced by implantation of a bone morphogenetic protein (BMP)-2-containing collagen pellet in mouse muscular tissue. However, the character of circulating bone marrow-derived osteoblast progenitor cells (MOPCs) and the precise mechanisms involving the circulating MOPCs in the osteogenic processes, such as signals that recruit the circulating MOPCs to the osseous tissues, have been obscure. In this report, we demonstrated for the first time that the MOPCs were mobilized from intact bones to transiently occupy approximately 80% of the mononuclear cell population in the circulating blood by BMP-2-pellet implantation. The mobilized MOPCs in the circulation did not express the hematopoietic marker CD45 on their surface, but they expressed CD44 and CXCR4, receptors of osteopontin and stromal cell-derived factor-1 (SDF-1), respectively. The MOPCs isolated from the mouse peripheral blood showed the ability to be osteoblasts in vitro and in vivo. Furthermore, the MOPCs in the circulation efficiently migrated to the region of bone formation by chemoattraction of SDF-1 expressed in vascular endothelial cells and the de novo osteoblasts of the region. These data may provide a novel insight into the mechanism of bone formation involving MOPCs in circulating blood, as well as perspective on the use of circulating MOPCs to accelerate bone regeneration in the future.

Disclosure of potential conflicts of interest is found at the end of this article.
Rapid Adhesion to Collagen Isolates Murine Keratinocytes with Limited Long-Term Repopulating Ability In Vivo Despite High Clonogenicity In Vitro
Authors: Strachan Lauren R. , Scalapino Kenneth J. , Lawrence H. Jeffery , Ghadially Ruby
Published: October 2007

A prevalent belief in epidermal biology is that stem cells are highly clonogenic; that is, they have the ability to produce many large colonies in vitro. However, it has been well-established in hematology, and recently suggested in epithelial biology, that short-term in vitro clonogenic assays may not be reliable predictors of long-term in vivo repopulating ability. Numerous groups have shown that rapid adhesion to collagen selects for highly clonogenic keratinocytes, but it has not been demonstrated whether this subpopulation is enriched in stem cells as defined by long-term repopulating ability in vivo. We found that although rapid adhesion to collagen (within 5 minutes) selected for cells with increased short-term colony forming ability in vitro, these cells were not enriched in long-term proliferative ability in vitro or in repopulating ability in vivo after 9 weeks. Conversely, keratinocytes that did not adhere to collagen (after 20 minutes) were less clonogenic in short-term assays but possessed equivalent long-term proliferative ability in vitro and superior long-term repopulating ability in vivo. Both the rapidly adherent cell and not rapidly adherent cell populations contained small, noncomplex basaloid cells, expressed integrin α2 (a collagen IV receptor), and expressed the putative epidermal stem cell phenotype integrin α6hiCD71lo. Our results indicate that the superior short-term colony forming ability of collagen-adherent murine keratinocytes does not correlate with long-term repopulating ability in vitro or in vivo and that proliferation in vitro is not a reliable surrogate for stem cell behavior in vivo.

Disclosure of potential conflicts of interest is found at the end of this article.
Age- and Dose-Related Effects on MSC Engraftment Levels and Anatomical Distribution in the Central Nervous Systems of Nonhuman Primates: Identification of Novel MSC Subpopulations That Respond to Guidance Cues in Brain
Authors: Isakova Iryna A. , Baker Kate , DuTreil Maria , Dufour Jason , Gaupp Dina , Phinney Donald G.
Published: October 2007

Mesenchymal stem cells (MSCs) have demonstrated efficacy as therapeutic vectors in rodent models of neurological diseases, but few studies have evaluated their safety and efficacy in a relevant large animal model. Previously, we reported that MSCs transplanted to the central nervous systems (CNS) of adult rhesus macaques engrafted at low levels without adversely affecting animal health, behavior, or motor function. Herein, we injected MSCs intracranially into 10 healthy infant macaques and quantified their engraftment levels and mapped their anatomical distribution in brain by real-time polymerase chain reaction using an sry gene-specific probe. These analyses revealed that MSC engraftment levels in brain were on average 18-fold higher with a maximal observed difference of 180-fold in neonates as compared with that reported previously for young adult macaques. Moreover, engraftment levels were 30-fold higher after injection of a low versus high cell dose and engrafted MSCs were nonrandomly distributed throughout the infant brain and localized to specific anatomical regions. Identification of unique subpopulations of macaque and human MSCs that express receptor proteins known to regulate tangential migration of interneurons may explain their migration patterns in brain. Extensive monitoring of infant transplant recipients using a battery of age appropriate tests found no evidence of any long-term adverse effects on the health or social, behavioral, cognitive, or motor abilities of animals up to 6 months post-transplant. Therefore, direct intracranial injection represents a safe means to deliver therapeutic levels of MSCs to the CNS. Moreover, expressed guidance receptors on MSC subpopulations may regulate migration of cells in the host brain.

Disclosure of potential conflicts of interest is found at the end of this article.
Human Leukocyte Antigen-G5 Secretion by Human Mesenchymal Stem Cells Is Required to Suppress T Lymphocyte and Natural Killer Function and to Induce CD4+CD25highFOXP3+ Regulatory T Cells
Authors: Selmani Zohair , Naji Abderrahim , Zidi Ines , Favier Benoit , Gaiffe Emilie , Obert Laurent , Borg Christophe , Saas Philippe , Tiberghien Pierre , Rouas-Freiss Nathalie , Carosella Edgardo D. , Deschaseaux Frederic
Published: October 2007

Adult bone marrow-derived mesenchymal stem cells (MSCs) are multipotent cells that are the subject of intense investigation in regenerative medicine. In addition, MSCs possess immunomodulatory properties with therapeutic potential to prevent graft-versus-host disease (GvHD) in allogeneic hematopoietic cell transplantation. Indeed, MSCs can inhibit natural killer (NK) function, modulate dendritic cell maturation, and suppress allogeneic T-cell response. Here, we report that the nonclassic human leukocyte antigen (HLA) class I molecule HLA-G is responsible for the immunomodulatory properties of MSCs. Our data show that MSCs secrete the soluble isoform HLA-G5 and that such secretion is interleukin-10-dependent. Moreover, cell contact between MSCs and allostimulated T cells is required to obtain a full HLA-G5 secretion and, as consequence, a full immunomodulation from MSCs. Blocking experiments using neutralizing anti-HLA-G antibody demonstrate that HLA-G5 contributes first to the suppression of allogeneic T-cell proliferation and then to the expansion of CD4+CD25highFOXP3+ regulatory T cells. Furthermore, we demonstrate that in addition to their action on the adaptive immune system, MSCs, through HLA-G5, affect innate immunity by inhibiting both NK cell-mediated cytolysis and interferon-γ secretion. Our results provide evidence that HLA-G5 secreted by MSCs is critical to the suppressive functions of MSCs and should contribute to improving clinical therapeutic trials that use MSCs to prevent GvHD.

Disclosure of potential conflicts of interest is found at the end of this article.
Revisiting OCT4 Expression in Peripheral Blood Mononuclear Cells
Authors: Kotoula Vassiliki , Papamichos Spyros I. , Lambropoulos Alexandros F.
Published: October 2007

The transcription factor OCT4 (officially POU5F1; alternatively OCT3, OCT3/4, OTF3, and OTF4) is currently considered a main regulator of human embryonic stem cell pluripotency and self-renewal capacities. Importantly, these stemness properties are attributed to OCT4A, which is one of the two isoforms produced by the OCT4 gene. The second OCT4 isoform, OCT4B, does not share the stemness factor characteristics of OCT4A and is currently considered of unknown function. Hence, when investigating OCT4 expression at the mRNA and protein level, it is important to specify which OCT4 isoform is detected by the applied methods, such as polymerase chain reaction assays and immunocytochemistry antibodies. Here, we discuss the need to distinguish between OCT4A and OCT4B when interpreting OCT4 expression in differentiated cells, such as peripheral blood mononuclear cells.

Disclosure of potential conflicts of interest is found at the end of this article.
Biodegradable municipal solid waste: biotreatment options
Authors: Banks C. J. , Stentiford E. I.
Published: October 2007

The context under which the UK Government plans to divert biodegradable municipal solid waste from landfill is described and the role that bioprocessing may play is presented. The concepts developed from different types of anaerobic processes and the differing possible process configurations are considered. The most commonly used options are then appraised on the basis of technical engineering operation and microbiological functionality. Some practical examples of system types are given, although these are not based on case studies. The long history of waste composting (aerobic bioprocessing) has meant that there are a large number of process systems on offer. The fundamentals behind the different types of process are considered, focusing on their overall aim of achieving sanitisation and stabilisation. The interrelationships between the key factors of particle size, aeration, nutrients and moisture content are considered together with how each of the generic systems seeks to manage them.
The South Shropshire biowaste digester, UK
Authors: Chesshire M.
Published: October 2007

The South Shropshire biowaste digester is designed to recycle 5000 t per year of source-segregated household kitchen waste and green garden waste. This waste, collected at the kerbside, is transformed into renewable electricity and biofertiliser. It is one of nine full-scale projects funded by the UK Department for Environment, Food and Rural Affairs (Defra) to demonstrate technologies that enable biodegradable municipal waste to be diverted from landfill. Previous research, over a period of eight years leading to the biowaste digester, concentrated on the anaerobic digestion of food waste, which is able to contribute to the positive reduction in the emission of greenhouse gases in a number of different ways. As a renewable energy technology, anaerobic digestion is unusual in that the overall net reduction in the emission of carbon dioxide is greater than simply the carbon dioxide emissions from the fossil fuels that it displaces; however, apart from its application on sewage works and in landfill sites, the process is not yet widely applied in the UK. The project met the necessary permitting requirements and construction started in June 2005. The first biowaste was processed in March 2006 and the plant is operating at 50% of its design throughput. The first year of operation has shown that the quality of the biowaste is very different from that anticipated, in particular with a low capture of food waste. This issue is being addressed in order that the project can demonstrate the effective role that anaerobic digestion can play in the UK's future waste management strategy.
An innovative in-vessel tunnel composting system
Authors: Webb A. L.
Published: October 2007

The batch tunnel composting demonstrator project under construction at St Ives, Cambridgeshire, UK, is one of a number of similar projects funded by the UK Department for Environment, Food and Rural Affairs as part of the New Technologies Demonstrator Programme (NTDP). The St Ives project includes the design, build and assessment of a new in-vessel composting plant and its demonstration to local authorities to highlight the central role of composting in efforts to divert biodegradable municipal waste (BMW) from landfill. Current statistics show that several million tonnes of BMW are landfilled each year in the UK, much of which could instead be composted. Assuming all current composting facilities are working at full capacity, over 100 new plants capable of processing 100 000 t per annum would be required to compost this volume of waste. The NTDP aims to present the technical, environmental and economic viability of new techniques to divert BMW from landfill and encourage the construction of further processing facilities. The new St Ives composting plant will be equipped with an innovative system to heat the walls and floors of the tunnel in order to ensure the entire composting mass reaches the temperatures specified by the 2005 Animal By-Product Regulations (ABPR) and reduce the risk of cold spots. The project will assess the effectiveness of this heating system.
Rotary in-vessel advanced aerobic composting
Authors: Box N.
Published: October 2007

This paper describes the adaptation and development of a rotary in-vessel advanced composting system for source-separated garden and kitchen waste, food industry waste and other biodegradable municipal waste (BMW) as part of the UK Department for Environment, Food and Rural Affairs (Defra) New Technologies Demonstrator Programme. Over the life of the project, the plant aims to convert 10 000 t of BMW into high-grade fertiliser to be supplied to the agricultural market. Investigation and development work carried out in connection with an end market for the product is also summarised.
Briefing: Defra's New Technologies Demonstrator Programme
Authors: Brooks D. , Powrie W.
Published: October 2007

The EU Landfill Directive sets targets that the UK must meet in respect of the diversion of biodegradable municipal waste away from landfill. This paper describes a programme established by the UK Department for Environment, Food and Rural Affairs (Defra) to encourage the development and implementation of new technologies to help achieve these targets. The core of this programme is a series of demonstrator projects; supporting research, education and awareness activities are also summarised.
Genetic parameters for wool traits in Finnsheep lambs
Authors: PUNTILA M-L. , MÄKI K. , NYLANDER A.
Published: October 2007

Genetic parameters were estimated for wool characteristics of white and coloured Finnsheep. The data consisted of 5 309 lambs from ordinary production flocks, the Finnsheep nucleus flock and a breeding flock. The variance component estimation was done applying REML analyses. Wool traits included fleece uniformity, density, staple formation, lustre, crimp frequency, fineness grade and staple length. There was a smaller dataset that contained also lamb live weight, greasy fleece weight and additional fleece characteristics including fibre diameter measured with the OFDA method. The variance components for direct and maternal effects were estimated using bivariate analysis for 42-day, 120-day weight and greasy fleece weight. Heritability for visually assessed wool characteristics varied from 0.23 to 0.43 and for measured traits from 0.45 to 0.62. Staple length had a high negative genetic correlation with crimp frequency and fineness grade. Heritability of greasy fleece weight was high (0.55) and that of fibre diameter 0.62. The genetic correlation between crimp frequency and fibre diameter was negative (- 0.56). The results imply that the assessed traits are useful indicators for fleece quality and those of major importance can be introduced into the breeding programme. The results suggest that there is no antagonism in selection for both growth capacity and wool quantity.;
Genetic parameters for Finnish blue fox population: litter size, age at first insemination and pelt size
Authors: PEURA J. , STRANDÉN I. , MÄNTYSAARI E.A.
Published: October 2007

Pelt size has increased rapidly in the Finnish blue fox population during the last decade. However, average number of pups per mated female has slightly decreased after the mid-1990s. In this study we estimated genetic parameters of litter size in the first two parturitions, age of female at first insemination, and pelt size with a linear multitrait animal model. Heritability of litter size in first and second parturition was 0.06 and 0.10, respectively. Heritability estimate for age at first insemination was 0.15 and for pelt size 0.29. Genetic correlation between pelt size and first litter size was 0.30, between first and second litter size 0.76, and between second litter size and age at first insemination 0.70. Thus, genetic correlation between fertility and pelt size was unfavorable.;
Genetic variation of loin and ham quality in Finnish Landrace and Large White pigs
Authors: SEVÓN-AIMONEN M-L. , HONKAVAARA M. , SERENIUS T.
Published: October 2007

Selection potential for meat quality of economically important loin (longissimus) and ham muscles (adductor, semimembranosus, biceps femoris) has been assessed. Ultimate pH (pHu), meat colour (lightness, redness and yellowness), drip loss and two visually scored colour traits were recorded from 483 Finnish Landrace and 494 Finnish Large White station test pigs in a half-sib design. A univariate restricted maximum likelihood procedure was used to estimate variance components. The statistical model contained age at beginning of test, sex and time lapse from slaughter to dissection as fixed effects and slaughter batch, common environment of littermates and additive genetic effect of the animal as random effects. The average pHu values in adductor and semispinalis were between 5.6 and 6.1. The pHu were on average 5.4 and 5.5 in longissimus and semimembranosus respectively, with the latter two being lower than optimum values of 5.6 to 5.9. Lightness for semimembranosus turned to be clearly lighter (62) than for other muscles. Lightness for longissimus (56) was slightly lighter than optimum (from 48 to 54). The heritability varied from zero to 0.45 for pHu, from 0.02 to 0.34 for lightness, from 0.17 to 0.56 for redness, from zero to 0.28 for yellowness and from 0.05 to 0.16 for drip loss. Heritability for redness values was considerably higher than heritability for other meat quality traits. The heritability of quality traits spoke for possibilities for genetic improvement of meat quality. Genetic correlations between quality traits (pHu and lightness) and average daily gain varied strongly among breeds and muscles. Genetic correlations between meat-% and pHu were in most cases high and unfavourable (rg from 0.36 to 0.68 except in longissimus, where it was 0.11). Genetic correlations between meat-% and lightness were unfavourable in Finnish Large White (from 0.47 to 0.92) but in Finnish Landrace estimates varied among muscles (from 0.40 to 0.47). Due to these results, the ham quality (pHu and lightness for semimembranosus) was included in the selection criteria for pork quality in the Finnish pig improvement programme.;
An overview on quantitative and genomic tools for utilising dominance genetic variation in improving animal production
Authors: MÄKI-TANILA A.
Published: October 2007

In addition to genetic progress made by selection on additive genetic values, short-term gains can be produced by recovering possible inbreeding depression or utilising putative overdominance. These are both caused mainly by dominance genetic variation which can be quantified using mixed model methodology. Inbreeding brings along a requirement for extra parameterisation in expressing and estimating dominance variance. The extra parameters specify how dominance is affecting the mean and (co)variances among inbred animals. The full description for breed crosses contains a very large set of parameters. The benefits from crossbreeding are highest with widely deviating allele frequencies between the breeds. Maximisation of heterosis can be done only on a temporary basis as a continued exploitation leads to stagnation in the overall genetic progress. Therefore efficient methods with immediate returns are needed to find the most promising breeds jointly with the most potential mating pairs. One possibility is the use of genomic tools in assessing populations for crossbreeding and in searching for major genes mediating dominance variation. The analyses are providing markers that can be used in choosing mating pairs that produce desirable dominance deviations in analysed marker brackets. Genome-wide marker sets can be used for discovering genome segments with maximum heterosis effect. The phenotypic records are available for such analyses, soon are also the large marker sets and their genotypes: the analytical tools need developers.;
Molecular genetic variation in sheep of the central Volga area inhabited by Finno-Ugric peoples
Authors: TAPIO M. , OZEROV M. , VIINALASS H.
Published: October 2007

Based on morphology, native northern European sheep breeds belong to the short tailed type, of which the Romanov is the only native example still distributed in northwest Russia. Besides this, there exist local sheep populations kept by Finno-Ugric peoples in the central Volga region, which represent additional genetic resources in the area. Four sheep populations from the central Volga region were genotyped for 20 microsatellites and compared with geographically proximate breeds (Estonian Whitehead and Blackhead, the Finnsheep and an exported and a native population of Russian Romanov) and with local populations in Estonia, Finland and Russian Karelia. Between-breed analyses including admixture analysis using molecular genetic markers and the phenotypic characteristics indicated that the Volgaic populations have not remained pure. The Viena population from Russian Karelia, the Romanov breed and, to some extent, the Komi population, have escaped extensive mixing, making them most attractive for conservation programmes. The study compared imported and native Romanov breed populations and the results suggest that the diversity parameters are markedly similar in these two populations.;