bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gdnf Upregulates c-Fos Transcription via the Ras/Erk1/2 Pathway to Promote Mouse Spermatogonial Stem Cell Proliferation
Authors: He Zuping , Jiang Jiji , Kokkinaki Maria , Golestaneh Nady , Hofmann Marie-Claude , Dym Martin 
Published: October 2007

AbstractGlial cell line-derived neurotrophic factor (GDNF) plays a crucial role in regulating the proliferation of spermatogonial stem cells (SSC). The signaling pathways mediating the function of GDNF in SSC remain unclear. This study was designed to determine whether GDNF signals via the Ras/ERK1/2 pathway in the C18-4 cells, a mouse SSC line. The identity of this cell line was confirmed by the expression of various markers for germ cells, proliferating spermatogonia, and SSC, including GCNA1, Vasa, Dazl, PCNA, Oct-4, GFRα1, Ret, and Plzf. Western blot analysis revealed that GDNF activated Ret tyrosine phosphorylation. All 3 isoforms of Shc were phosphorylated upon GDNF stimulation, and GDNF induced the binding of the phosphorylated Ret to Shc and Grb2 as indicated by immunoprecipitation and Western blotting. The active Ras was induced by GDNF, which further activated ERK1/2 phosphorylation. GDNF stimulated the phosphorylation of CREB-1, ATF-1, and CREM-1, and c-fos transcription. Notably, the increase in ERK1/2 phosphorylation, c-fos transcription, bromodeoxyuridine incorporation, and metaphase counts induced by GDNF, was completely blocked by pretreatment with PD98059, a specific inhibitor for MEK1, the upstream regulator of ERK1/2. GDNF stimulation eventually upregulated cyclin A and CDK2 expression. Together, these data suggest that GDNF induces CREB/ATF-1 family member phosphorylation and c-fos transcription via the Ras/ERK1/2 pathway to promote the proliferation of SSC. Unveiling GDNF signaling cascades in SSC has important implications in providing attractive targets for male contraception as well as for the regulation of stem cell renewal vs. differentiation.Disclosure of potential conflicts of interest is found at the end of this article.
Toll-Like Receptors 3 and 4 Are Expressed by Human Bone Marrow-Derived Mesenchymal Stem Cells and Can Inhibit Their T-Cell Modulatory Activity by Impairing Notch Signaling
Authors: Liotta Francesco , Angeli Roberta , Cosmi Lorenzo , Filì Lucia , Manuelli Cinzia , Frosali Francesca , Mazzinghi Benedetta , Maggi Laura , Pasini Annalisa , Lisi Veronica , Santarlasci Veronica , Consoloni Lara , Angelotti Maria Lucia , Romagnani Paola , Parronchi Paola , Krampera Mauro , Maggi Enrico , Romagnani Sergio , Annunziato Francesco 
Published: October 2007

Abstract
Bone marrow (BM)-derived mesenchymal stem cells (MSCs) are multipotent, nonhemopoietic progenitors that also possess regulatory activity on immune effector cells through different mechanisms. We demonstrate that human BM-derived MSCs expressed high levels of Toll-like receptors (TLRs) 3 and 4, which are both functional, as shown by the ability of their ligands to induce nuclear factor κB (NF-κB) activity, as well as the production of interleukin (IL)-6, IL-8, and CXCL10. Of note, ligation of TLR3 and TLR4 on MSCs also inhibited the ability of these cells to suppress the proliferation of T cells, without influencing their immunophenotype or differentiation potential. The TLR triggering effects appeared to be related to the impairment of MSC signaling to Notch receptors in T cells. Indeed, MSCs expressed the Notch ligand Jagged-1, and TLR3 or TLR4 ligation resulted in its strong downregulation. Moreover, anti-Jagged-1 neutralizing antibody and N[N-(3,5-difluorophenacetyl-l-alanyl)]-S-phenylglycine t-butyl ester (DAPT), an inhibitor of Notch signaling, hampered the suppressive activity of MSCs on T-cell proliferation. These data suggest that TLR3 and TLR4 expression on MSCs may provide an effective mechanism to block the immunosuppressive activity of MSCs and therefore to restore an efficient T-cell response in the course of dangerous infections, such as those sustained by double-stranded RNA viruses or Gram-negative bacteria, respectively.
Disclosure of potential conflicts of interest is found at the end of this article.
Ribosomal Protein S19 Deficiency Leads to Reduced Proliferation and Increased Apoptosis but Does Not Affect Terminal Erythroid Differentiation in a Cell Line Model of Diamond-Blackfan Anemia
Authors: Miyake Koich , Utsugisawa Taiju , Flygare Johan , Kiefer Thomas , Hamaguchi Isao , Richter Johan , Karlsson Stefan 
Published: October 2007

Abstract
Diamond-Blackfan anemia (DBA) is a congenital red-cell aplasia in which 25% of the patients have a mutation in the ribosomal protein (RP) S19 gene. It is not known how the RPS19 deficiency impairs erythropoiesis and proliferation of hematopoietic progenitors. To elucidate molecular mechanisms in RPS19-deficient DBA, we analyzed the effects of RPS19 deficiency on erythropoietin (EPO)-induced signal transduction, cell cycle, and apoptosis in RPS19-deficient TF-1 cells. We did not find any abnormality in EPO-induced signal transduction. However, RPS19-deficient TF-1 cells showed G0/G1 arrest (82% vs. 58%; p &lt; .05) together with accumulation of p21 and p27. The fraction of apoptotic cells detected by Annexin V analysis also increased compared with control cells (13% vs. 3.1%; p &lt; .05). Western blot analysis of apoptosis-related proteins showed that the level of bcl-2 and Bad was decreased and Bax was increased in RPS19-deficient TF-1 cells. Moreover, primary CD34-positive cells from DBA patients detected by Annexin V analysis also generated a higher number of apoptotic cells compared with normal CD34-positive cells during in vitro culture (38% vs. 8.9%; n = 5; p &lt; .001). Finally, we show that although RPS19 silencing reduces EPO-induced development of erythroid progenitors expressing glycophorin A (GPA), RPS19 silencing in cells already expressing GPA does not affect GPA expression. These findings indicate that RPS19 deficiency causes apoptosis and accelerated loss of erythroid progenitors in RPS19-deficient DBA.
Disclosure of potential conflicts of interest is found at the end of this article.
The 5th International Society for Stem Cell Research (ISSCR) Annual Meeting, June 2007
Authors: Rajasekhar Vinagolu K. , Dalerba Piero , Passegué Emmanuelle , Lagasse Eric , Najbauer Joseph 
Published: October 2007

Abstract
This report presents highlights of discussions that focused on the biology of cancer stem cells as conducted at the fifth Annual Meeting of the International Society for Stem Cell Research, held in Cairns, Australia, June 17–20, 2007. The function of adult stem cells is believed to depend on their niches, that is, the microenvironment in which these stem cells reside. A similar concept applies to understanding the development of cancer, as it is becoming increasingly clear that only a small subset of cancer cell populations is capable of initiating/sustaining tumor formation. These tumorigenic cells, commonly referred to as cancer stem cells, also appear to reside in particular niches, and they bear the known, albeit dysfunctional, stem cell characteristics of self-renewal and differentiation. Dysregulation of stem cell niches is thought to contribute to tumorigenesis by affecting the complex network of signaling interactions that occur between stem cells and their neighboring cells, thus imbalancing the physiological controls on self-renewal and differentiation processes. This hypothesis was widely explored at the conference to shed new light on the mechanisms of tumor origin and progression and to unveil novel antitumor therapeutic approaches.
Disclosure of potential conflicts of interest is found at the end of this article.
The HOXB4 Homeoprotein Differentially Promotes Ex Vivo Expansion of Early Human Lymphoid Progenitors
Authors: Haddad Rima , Pflumio Françoise , Vigon Isabelle , Visentin Géraldine , Auvray Céline , Fichelson Serge , Amsellem Sophie 
Published: October 2007

Abstract
The HOXB4 homeoprotein is known to promote the expansion of mouse and human hematopoietic stem cells (HSCs) and progenitors of the myeloid lineages. However, the putative involvement of HOXB4 in lymphopoiesis and particularly in the expansion of early lymphoid progenitor cells has remained elusive. Based on the ability of the HOXB4 protein to passively enter hematopoietic cells, our group previously designed a long-term culture procedure of human HSCs that allows ex vivo expansion of these cells. Here, this method has been further used to investigate whether HOXB4 could cause similar expansion on cells originating from CD34+ hematopoietic progenitor cells (HPCs) committed at various levels toward the lymphoid lineages. We provide evidence that HOXB4 protein delivery promotes the expansion of primitive HPCs that generate lymphoid progenitors. Moreover, HOXB4 acts on lymphomyeloid HPCs and committed T/natural killer HPCs but not on primary B-cell progenitors. Our results clarify the effect of HOXB4 in the early stages of human lymphopoiesis, emphasizing the contribution of this homeoprotein in the maintenance of the intrinsic lymphomyeloid differentiation potential of defined HPC subsets. Finally, this study supports the potential use of HOXB4 protein for HSC and HPC expansion in a therapeutic setting and furthers our understanding of the mechanisms of the molecular regulation of hematopoiesis.
Disclosure of potential conflicts of interest is found at the end of this article.
Adenoviral Vector-Mediated Transfer of the Indian Hedgehog Gene Modulates Lymphomyelopoiesis In Vivo
Authors: Kobune Masayoshi , Kato Junji , Kawano Yutaka , Sasaki Katsunori , Uchida Hiroaki , Takada Kohichi , Takahashi Sho , Takimoto Rishu , Niitsu Yoshiro 
Published: October 2007

Abstract
Indian hedgehog (Ihh) plays an essential role in angiogenesis, hematogenesis, and epiphysis formation during embryogenesis. In the present study, we injected an adenoviral vector (Adv) carrying the mock-control (Adv-control) or Ihh (Adv-Ihh) gene into severe combined immunodeficiency (SCID) or BALB/c mice to evaluate the effects of lhh on the regulation of postnatal hematopoiesis in vivo. After the i.v. injection of Adv-Ihh, the expression of vector-derived Ihh mRNA was detected in the liver. Four weeks after administration of Adv-Ihh to SCID mice, we observed an increase in the number of c-Kit+ cells and clonogenic cells per 105 mononuclear cells in the bone marrow compared with Adv-control-administered mice. Moreover, after administration of Adv-Ihh to BALB/c mice, the number of splenic B220+IgMlowCD23intCD21int B lymphocytes and CD4+ T lymphocytes was strongly increased. Furthermore, the number of thymic double-negative (DN)2, DN3, CD8+ immature single-positive, and CD4+/CD8− cells was significantly elevated relative to the number in mice that received the control Adv vector. Our results suggest that enhanced signaling by Ihh can modulate the proliferation and differentiation of splenic B lymphocytes and thymic T lymphocytes during bone marrow hematopoiesis in vivo. Thus, modulation of the hedgehog signaling pathway may provide a therapeutic strategy to stimulate lymphomyelopoiesis in vivo.
Disclosure of potential conflicts of interest is found at the end of this article.
Tolerance (PICT) of the Bacterial Communities to Copper in Vineyards Soils from Spain
Authors: Díaz‐Raviña M. , de Anta R. Calvo , Bååth E. 
Published: October 2007

AbstractTo detect effects of Cu pollution, the Cu tolerance of soil bacterial communities extracted from several vineyards located in NW Spain was measured. Bacterial community tolerance was estimated by means of the thymidine (TdR) and leucine (Leu) incorporation techniques using either IC50 values (the log of the metal concentration that reduced incorporation to 50%) or the percentage of activity at one specific Cu concentration (10−6 mol L−1). The tolerance measurements by the TdR incorporation technique were similar to those obtained by the Leu incorporation method, indicating that the two methods were equivalent in terms of suitability for detecting the toxicity of Cu to soil bacterial communities. The two tolerance indices considered (IC50 values and percentage of activity) were closely correlated (r = 0.975, P < 0.001), showing that both were equally good in measuring Cu tolerance of the bacterial community. An increased bacterial community tolerance to Cu, indicating a pollution effect, was observed in vineyard soils with more than 100 mg Cu kg−1 soil. Thus, the long‐term use of Cu in vineyards has a toxic effect on the soil bacterial community, resulting in an increased tolerance. An effect of increased levels of Cu could not be detected when measuring bacterial community activity, pointing to the increased sensitivity to detect toxicity in field studies using tolerance measurements.
Responses of a Non–N‐Limited Forest Plantation to the Application of Alkaline‐Stabilized Dewatered Dairy Factory Sludge
Authors: Omil Beatriz , Mosquera‐Losada Rosa , Merino Agustín 
Published: October 2007

AbstractAmendment of forest soils with dewatered dairy factory sludge (DDFS), characterized by low heavy metal contents and high amounts of degradable C, can prevent the depletion of soil nutrients that results from intensive harvesting in forest plantations. However, this practice involves environmental risks when N supplies exceed the demand of plants or when the strong acidity of the soil favors the mobility of trace metals. These aspects were assessed in a young radiata pine plantation growing in a sandy, acidic, and organic N‐rich soil for the 7 yr after application of a DDFS. The supply of limiting nutrients (mainly P, Mg, and Ca) provided by application of the DDFS, along with control of the ground vegetation, improved the nutritional status of the stand and led to increases in timber volume of more than 60 to 100%. Increases in soil inorganic N were observed during the first months after amendment. Data from soil incubation experiments revealed that some of the additional N was immobilized and, to a lesser extent, denitrified due to the readily available organic C content of the DDFS. Leaching and increased plant uptake of N were prevented by a combination of the latter processes and the low rate of nitrification. The strong acidity of the soil enhanced the availability of Mn and Zn to plants, although the maximum concentrations did not reach levels harmful to organisms. We conclude that although application of DDFS has positive effects on tree nutrition and growth and the environmental risks are low, repeated application may favor mobility of N and availability of heavy metals.
The Treatment Performance of Different Subsoils in Ireland Receiving On‐Site Wastewater Effluent
Authors: Gill L. W. , O'Súlleabháin C. , Misstear B. D. R. , Johnston P. J. 
Published: October 2007

AbstractCurrent Irish guidelines require a comprehensive site assessment of a percolation area for wastewater disposal before planning permission is granted for dwellings in rural areas. For a site to be deemed suitable, the subsoil must have a percolation value equivalent to a field saturated hydraulic conductivity in the range 0.08 to 4.2 m d−1 using a falling head percolation test. A minimum of 1.2 m of unsaturated subsoil must also exist below the invert of the percolation area receiving effluent from a septic tank (or 0.6 m for secondary treated effluent). During a 2‐yr period, the three‐dimensional performance of four percolation areas treating domestic wastewater was monitored. At each site samples were taken at 0, 10, and 20 m along each of the four percolation trenches at depths of 0.3, 0.6, and 1.0 m below each trench to ascertain the attenuation effects of the unsaturated subsoil. The two sites with septic tanks installed performed at least as well as the other two sites with secondary treatment systems installed and appeared to discharge a better quality effluent in terms of nutrient load. An average of 2.1 and 6.8 g total N d−1 remained after passing through 1‐m depth of subsoil beneath the trenches receiving septic tank effluent compared with 12.7 and 16.7 g total N d−1 on the sites receiving secondary effluent. The research also indicates that the septic tank effluent was of an equivalent quality to the secondary treated effluent in terms of indicator bacteria (E. coli) after percolating through 0.6‐m depth of unsaturated subsoil.
The Leaching Characteristics of Selenium from Coal Fly Ashes
Authors: Wang Tian , Wang Jianmin , Burken Joel G. , Ban Heng , Ladwig Ken 
Published: October 2007

AbstractThe leaching characteristics of selenium from several bituminous and subbituminous coal fly ashes under different pH conditions were investigated using batch methods. Results indicated that pH had a significant effect on selenium leaching from bituminous coal ash. The minimum selenium leaching occurred in the pH range between 3 and 4, while the maximum selenium leaching occurred at pH 12. The release of selenium from subbituminous coal ashes was very low for the entire experimental pH range, possibly due to the high content of calcium which can form hydration or precipitation products as a sink for selenium. The adsorption results for different selenium species indicated that Se(VI) was hardly adsorbable on either bituminous coal ashes or subbituminous coal ashes at any pH. However, Se(IV) was highly adsorbed by bituminous coal ashes under acidic pH conditions and was mostly removed by subbituminous coal ashes across the entire pH range. This result suggests that the majority of selenium released from the tested fly ashes was Se(IV). A speciation‐based model was developed to simulate the adsorption of Se(IV) on bituminous coal fly ash, and the pH‐independent adsorption constants of HSeO3− and SeO32− were determined. The modeling approach is useful for understanding and predicting the release process of selenium from fly ash.
Soil Water Nitrate and Ammonium Dynamics under a Sewage Effluent–Irrigated Eucalypt Plantation
Authors: Livesley S. J. , Adams M. A. , Grierson P. F. 
Published: October 2007

AbstractManaged forests and plantations are appropriate ecosystems for land‐based treatment of effluent, but concerns remain regarding nutrient contamination of ground‐ and surface waters. Monthly NO3–N and NH4–N concentrations in soil water, accumulated soil N, and gross ammonification and nitrification rates were measured in the second year of a second rotation of an effluent irrigated Eucalyptus globulus plantation in southern Western Australia to investigate the separate and interactive effects of drip and sprinkler irrigation, effluent and water irrigation, irrigation rate, and harvest residues retention. Nitrate concentrations of soil water were greater under effluent irrigation than water irrigation but remained <15 mg L−1 when irrigated at the normal rate (1.5–2.0 mm d−1), and there was little evidence of downward movement. In contrast, NH4–N concentrations of soil water at 30 and 100 cm were generally greater under effluent irrigation than water irrigation when irrigated at the normal rate because of direct effluent NH4–N input and indirect ammonification of soil organic N. Drip irrigation of effluent approximately doubled peak NO3–N and NH4–N concentrations in soil water. Harvest residue retention reduced concentrations of soil water NO3–N at 30 cm during active sprinkler irrigation, but after 1 yr of irrigation there was no significant difference in the amount of N stored in the soil system, although harvest residue retention did enhance the “nitrate flush” in the following spring. Gross mineralization rates without irrigation increased with harvest residue retention and further increased with water irrigation. Irrigation with effluent further increased gross nitrification to 3.1 mg N kg−1 d−1 when harvest residues were retained but had no effect on gross ammonification, which suggested the importance of heterotrophic nitrification. The downward movement of N under effluent irrigation was dominated by NH4–N rather than NO3–N. Improving the capacity of forest soils to store and transform N inputs through organic matter management must consider the dynamic equilibrium between N input, uptake, and immobilization according to soil C status, and the effect changing microbial processes and environmental conditions can have on this equilibrium.
Glucose Control, Self-Care Behaviors, and the Presence of the Chronic Care Model in Primary Care Clinics
Authors: Parchman Michael L. , Pugh Jacqueline A. , Wang Chen-Pin , Romero Raquel L. 
Published: October 2007

OBJECTIVE—The purpose of this study was to examine the relationship between A1C and the extent to which care delivered to patients with type 2 diabetes in primary care clinics is consistent with the chronic care model (CCM), after controlling for self-care behaviors.
RESEARCH DESIGN AND METHODS—This was a cross-sectional, observational study of care provided to 618 patients with type 2 diabetes across 20 small, autonomous primary care clinics in South Texas. Subjects completed an exit survey. The medical record was abstracted for A1C values. Clinicians completed the Assessment of Chronic Illness Care (ACIC) survey, a validated measure of the extent to which care delivered is consistent with the CCM.
RESULTS—There was a significant relationship between ACIC score and A1C, but this relationship varied according to self-care behavior for exercise and was strongest for those who did not adhere to exercise recommendations: for every 1-point increase in ACIC score, A1C was 0.144% lower (P &lt; 0.001). The relationship between ACIC score and A1C for those who adhered to their diet was similar to that for those who did not, after adjusting for exercise, but the overall level of control was better for those who adhered to their diet.
CONCLUSIONS—Characteristics of the primary care clinic where one receives care are an important predictor of glucose control. If resources for implementing the CCM are limited, one might want to focus on clinics with low ACIC scores that serve a population of patients who are sedentary because this population may be likely to realize the most benefit from improved glucose control.
Exploring the Substitution of Exenatide for Insulin in Patients With Type 2 Diabetes Treated With Insulin in Combination With Oral Antidiabetes Agents
Authors: Davis Stephen N. , Johns Don , Maggs David , Xu Hangtao , Northrup Justin H. , Brodows Robert G. 
Published: October 2007

OBJECTIVE— This 16-week study explored the safety of substituting exenatide for insulin in patients with type 2 diabetes using insulin in combination with oral antidiabetes agents.
RESEARCH DESIGN AND METHODS— Successful maintenance of glycemic control was predefined as an A1C increase of &lt;0.5%. A total of 49 patients (aged 53 ± 8 years, with BMI 34 ± 4 kg/m2, A1C 8.1 ± 1.1%, and duration of diabetes 11 ± 7 years) were randomized to either substitute exenatide for insulin or remain on their current insulin regimen. Patients who either completed ≥8 weeks of study or discontinued because of loss of glycemic control were included in primary efficacy analysis.
RESULTS— A total of 62% (18 of 29) of the exenatide-treated patients maintained glycemic control compared with 81% (13 of 16) of the insulin-treated patients. Of the 11 exenatide-treated patients who did not maintain control, 5 discontinued before week 16 because of loss of glucose control. The overall safety profile was generally consistent with previous exenatide trials. The mean overall hypoglycemia rates were 1.72 and 0.97 events/patient-year for the exenatide and insulin reference groups, respectively.
CONCLUSIONS— This pilot study suggests that it is feasible to sustain glycemic control when substituting exenatide for insulin. Although it is not possible to characterize clear predictors of outcome given the size and exploratory nature of the study, the data suggest that patients with longer disease duration, who are taking higher doses of insulin and have less endogenous β-cell function, may experience deterioration in glucose control if exenatide is substituted for insulin therapy.