bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isolation and Characterization of Unsaturated Fatty Acid Auxotrophs ofStreptococcus pneumoniaeandStreptococcus mutans
Authors: Altabe Silvia , Lopez Paloma , de Mendoza Diego 
Published: September 2007

ABSTRACTUnsaturated fatty acid (UFA) biosynthesis is essential for the maintenance of membrane structure and function in many groups of anaerobic bacteria. LikeEscherichia coli, the human pathogenStreptococcus pneumoniaeproduces straight-chain saturated fatty acids (SFA) and monounsaturated fatty acids. InE. coliUFA synthesis requires the action of two gene products, the essential isomerase/dehydratase encoded byfabAand an elongation condensing enzyme encoded byfabB. S. pneumoniaelacks both genes and instead employs a single enzyme with only an isomerase function encoded by thefabMgene. In this paper we report the construction and characterization of anS. pneumoniae708fabMmutant. This mutant failed to grow in complex medium, and the defect was overcome by addition of UFAs to the growth medium.S. pneumoniae fabMmutants did not produce detectable levels of monounsaturated fatty acids as determined by gas chromatography-mass spectrometry and thin-layer chromatography analysis of the radiolabeled phospholipids. We also demonstrate that afabMnull mutant of the cariogenic organismStreptococcus mutantsis a UFA auxotroph, indicating that FabM is the only enzyme involved in the control of membrane fluidity in streptococci. Finally we report that thefabNgene ofEnterococcus faecalis, coding for a dehydratase/isomerase, complements the growth ofS. pneumoniae fabMmutants. Taken together, these results suggest that FabM is a potential target for chemotherapeutic agents against streptococci and thatS. pneumoniaeUFA auxotrophs could help identify novel genes encoding enzymes involved in UFA biosynthesis.
Costimulatory blockade of CD154-CD40 in combination with T-cell lymphodepletion results in prevention of allogeneic sensitization
Authors: Xu Hong , Yan Jun , Huang Yiming , Chilton Paula M. , Ding Chuanlin , Schanie Carrie L. , Wang Li , Ildstad Suzanne T. 
Published: September 2007

AbstractSensitization is a critical unresolved challenge in transplantation. We show for the first time that blockade of CD154 alone or combined with T-cell depletion prevents sensitization. Allogeneic skin grafts were rejected by recipients treated with anti-αβ T-cell receptor (TCR), anti-CD154, anti-OX40L, or anti–inducible costimulatory pathway (ICOS) mAb alone with a kinetic similar to untreated recipients. However, the production of anti–donor MHC antibody was prevented in mice treated with anti-CD154 mAb only, suggesting a specific role for the CD154-CD40 pathway in B-cell activation. The impairment of T cell–dependent B-cell responses by blocking CD154 occurs through inhibiting activation of T and B cells and secretion of IFN-γ and IL-10. Combined treatment with both anti-CD154 and anti–αβ TCR abrogated antidonor antibody production and resulted in prolonged skin graft survival, suggesting the induction of both T- and B-cell tolerance with prevention of allogeneic sensitization. In addition, we show that the tolerance induced by combined treatment was nondeletional. Moreover, these sensitization-preventive strategies promote bone marrow engraftment in recipients previously exposed to donor alloantigen. These findings may be clinically relevant to prevent allosensitization with minimal toxicity and point to humoral immunity as playing a dominant role in alloreactivity in sensitized recipients.
Giant panda BAC library construction and assembly of a 650-kb contig spanning major histocompatibility complex class II region
Authors: Zeng Chang-Jun , Pan Hui-Juan , Gong Shao-Bin , Yu Jian-Qiu , Wan Qiu-Hong , Fang Sheng-Guo 
Published: September 2007

Abstract

Background
Giant panda is rare and endangered species endemic to China. The low rates of reproductive success and infectious disease resistance have severely hampered the development of captive and wild populations of the giant panda. The major histocompatibility complex (MHC) plays important roles in immune response and reproductive system such as mate choice and mother-fetus bio-compatibility. It is thus essential to understand genetic details of the giant panda MHC. Construction of a bacterial artificial chromosome (BAC) library will provide a new tool for panda genome physical mapping and thus facilitate understanding of panda MHC genes.

Results
A giant panda BAC library consisting of 205,800 clones has been constructed. The average insert size was calculated to be 97 kb based on the examination of 174 randomly selected clones, indicating that the giant panda library contained 6.8-fold genome equivalents. Screening of the library with 16 giant panda PCR primer pairs revealed 6.4 positive clones per locus, in good agreement with an expected 6.8-fold genomic coverage of the library. Based on this BAC library, we constructed a contig map of the giant panda MHC class II region from BTNL2 to DAXX spanning about 650 kb by a three-step method: (1) PCR-based screening of the BAC library with primers from homologous MHC class II gene loci, end sequences and BAC clone shotgun sequences, (2) DNA sequencing validation of positive clones, and (3) restriction digest fingerprinting verification of inter-clone overlapping.

Conclusion
The identifications of genes and genomic regions of interest are greatly favored by the availability of this giant panda BAC library. The giant panda BAC library thus provides a useful platform for physical mapping, genome sequencing or complex analysis of targeted genomic regions. The 650 kb sequence-ready BAC contig map of the giant panda MHC class II region from BTNL2 to DAXX, verified by the three-step method, offers a powerful tool for further studies on the giant panda MHC class II genes.
Higher maturity and connective tissue association distinguish resident from ecently generated human tonsil plasma cells
Authors: Medina Francisco , Segundo Carmen , Jiménez-Gómez Gema , González-García Inés , Campos-Caro Antonio , Brieva José A 
Published: September 2007

AbstractHuman plasma cells (PC) are present in cell suspensions obtained from the tonsil by mechanical disaggregation (PCMECH). The present study shows that a collagenase treatment of tonsillar debris remaining after mechanical disaggregation yielded similar proportions of PC (PCCOLL). Moreover, PCMECH were present in suspensions highly enriched in germinal center cells whereas PCCOLL contained most of the IgA-secreting cells, suggesting their predominant location in follicular and parafollicular areas and connective tissue-rich zones such as tonsil subepithelium, respectively. Tonsil PCMECH and PCCOLL shared the phenotype CD38high CD19+ CD20low CD45high, expressed equivalent amounts of PRDI BF1/Blimp-1 transcription factor, and carried similarly mutated IgVH6 genes. However, they differed in several features. 1) PCMECH still expressed the early B cell transcription factor BSAP and were HLA-DRhigh; in contrast, PCCOLL were BSAP−and HLA-DRlow. 2) PCMECH were CD95+ and Bcl-2+/− whereas PCCOLL showed CD95+/− and Bcl-2+ expression; in addition, PCMECH exhibited increased spontaneous apoptosis. 3) The two PC subsets exhibited distinctive adhesion molecule profiles, since PCCOLL expressed higher levels of CD31, CD44, and CD49d, but a lower level of CD11a than PCMECH. These results suggest that PCMECH are recently generated, short-living PC, and PCCOLL constitutes a subset with higher maturity and survival, which resides in connective tissue-rich areas.
Stimulation of angiostatic platelet factor-4 variant (CXCL4L1/PF-4var) versus inhibition of angiogenic granulocyte chemotactic protein-2 (CXCL6/GCP-2) in normal and tumoral mesenchymal cells
Authors: Vandercappellen Jo , Noppen Samuel , Verbeke Hannelien , Put Willy , Conings René , Gouwy Mieke , Schutyser Evemie , Proost Paul , Sciot Raf , Geboes Karel , Opdenakker Ghislain , Van Damme Jo , Struyf Sofie 
Published: September 2007

AbstractChemokines affect inflammation and cancer through leukocyte attraction and angiogenesis. Here, we demonstrate that CXCL4L1/platelet factor-4 variant (PF-4var), a highly angiostatic chemokine, is poorly chemotactic for phagocytes and is inducible in monocytes by inflammatory mediators but remained undetectable in macrophages and neutrophils. In addition, CXCL4L1/PF-4var production by mesenchymal tumor cells was evidenced in vitro and in vivo by specific ELISA and immunohistochemistry. CXCL4L1/PF-4var, but not CXCL4/PF-4, was coinduced with the angiogenic chemokine CXCL6/granulocyte chemotactic protein-2 (GCP-2) by cytokines, e.g., IL-1β and IL-17, in sarcoma cells, but not in diploid fibroblasts. Furthermore, the induction of CXCL6/GCP-2 in endothelial cells by IL-1β was enhanced synergistically by TNF-α but inhibited by IFN-γ, which synergized with IL-1β to produce the angiostatic CXCL10/IFN-γ-induced protein-10. These findings indicate that the equilibrium between angiostatic and angiogenic factors during inflammation and tumor progression is rather complex and differs depending on the chemokine, cell type, and stimulus. Selective intervention in the chemokine network may drastically disturb this delicate balance of angiogenesis and tissue repair. Application of angiostatic CXCL4L1/PF-4var without attraction of protumoral phagocytes may be beneficial in cancer therapy.
Dap12 expression in activated microglia from retinoschisin-deficient retina and its PU.1-dependent promoter regulation
Authors: Weigelt Karin , Ernst Wolfgang , Walczak Yana , Ebert Stefanie , Loenhardt Thomas , Klug Maja , Rehli Michael , Weber Bernhard H F , Langmann Thomas 
Published: September 2007

AbstractSeveral alterations in the expression of immune-related transcripts were identified recently in the degenerating retina of the retinoschisin knockout (Rs1h−/Y) mouse, including the strong expression of the adaptor protein Dap12. As Dap12 is found in leukocytes, we hypothesized that its disease-related expression may be confined to activated retinal microglia cells. To test this hypothesis, we established a procedure for isolation and culture of retinal microglia cells and performed genome-wide expression profiling from Rs1h−/Y and control microglia. While retaining their activated state in culture, ex vivo microglia expressed high levels of Dap12 and the transcription factor PU.1. The activation-dependent induction of Dap12 was also confirmed in the microglia cell line BV-2 following in vitro stimulation. To examine the transcriptional regulation of Dap12 further, macrophage cell lines were transfected with several Dap12 reporter constructs. Promoter deletion assays and site-directed mutagenesis experiments demonstrated an essential role of evolutionarily conserved PU.1 consensus sites in the proximal −104/+118 Dap12 promoter. In vitro and in vivo binding of PU.1 to this promoter region was demonstrated using EMSA and chromatin immunoprecipitation. Knockdown of PU.1 by RNA interference caused a significant reduction of endogenous Dap12 expression and re-expression, and activation of PU.1 in PU.1−/− progenitor cells induced Dap12 transcription. Taken together, our results indicate that activated microglia from degenerating retinae express high levels of Dap12 and PU.1, and PU.1 controls the myeloid-specific regulation of Dap12 directly and may also play a general role in microglia gene expression during retinal degeneration.
Nose-to-brain delivery of tacrine
Authors: Jogani Viral V , Shah Pranav J , Misra Ambikanandan R , Mishra Pushpa , Mishra Anil Kumar 
Published: September 2007

Abstract
In the treatment of Alzheimer's disease tacrine, a cholinesterase inhibitor, is not the drug of choice due to its low oral bioavailability, extensive hepatic first-pass effect, rapid clearance from the systemic circulation, pronounced hepatotoxicity, and the availability of drugs better than tacrine in the same pharmacological class. Hence, the aim of this investigation was to ascertain the possibility of direct nose-to-brain delivery of tacrine to improve bioavailability, to avoid the first-pass effect and to minimize hepatotoxicity. Tacrine solution (TS) in propylene glycol was radiolabelled with 99mTc (technetium) and administered in BALB/c mice intranasally (i.n.) and intravenously (i.v.). Drug concentrations in blood and brain were determined at predetermined time intervals post dosing. Drug targeting efficiency (DTE %) and the brain drug direct transport percentage (DTP %) were calculated to evaluate the brain targeting efficiency. Brain scintigraphy imaging in rabbits was performed to ascertain the uptake of the drug into the brain. Tacrine solution was effectively labelled with 99mTc and was found to be stable and suitable for in-vivo studies. Following intranasal administration tacrine was delivered quickly (Tmax 60 min) to the brain compared with intravenous administration (Tmax 120 min). The brain/blood ratios of the drug were found to be higher for [99mTc]TSi.n. compared with [99mTc]TSi.v. at all time points. The DTE (207.23%) and DTP (51.75%) following intranasal administration suggested that part of tacrine was directly transported to brain from the nasal cavity. Rabbit brain scintigraphy imaging showed higher uptake of the drug into the brain following intranasal administration compared with intravenous administration. The results showed that tacrine could be directly transported into the brain from the nasal cavity and intranasal administration resulted in higher bioavailability of drug with reduced distribution into non-targeted tissues. This selective localization of tacrine in the brain may be helpful in reducing dose, frequency of dosing and dose-dependent side effects, and may prove an interesting new approach in delivery of the drug to the brain for the treatment of Alzheimer's disease.
The protective role of Kangen-karyu against fructose-induced metabolic syndrome in a rat model
Authors: Yokozawa Takako , Kim Hyun Ju , Yamabe Noriko , Okamoto Takuya , Cho Eun Ju 
Published: September 2007

Abstract
The protective effect of Kangen-karyu extract and its mechanisms against fructose-induced metabolic syndrome have been investigated using a rat model. Male Wistar rats were fed a high fructose (65%) diet or standard chow for one week, and for two subsequent weeks were treated with 50 or 100 mg kg−1 body weight/day Kangen-karyu extract or vehicle. Serum glucose, glycosylated protein, triglyceride (TG), total cholesterol, and blood pressure levels of high-fructose-fed rats were increased compared with those of normal rats. However, Kangen-karyu extract ameliorated the high-fructose-induced metabolic syndrome including hyperglycaemia and hypertriglyceridaemia. In addition, the increase of hepatic TG content in rats given the high fructose diet was significantly inhibited with the regulation of sterol regulatory element-binding protein (SREBP)-1 expression by Kangen-karyu extract. On the other hand, peroxisome proliferator-activated receptor α and SREBP-2 protein levels were not affected by the feeding of the high fructose diet or Kangen-karyu extract. Moreover, Kangen-karyu extract administration to high-fructose-fed rats markedly reduced the thiobarbituric acid-reactive substance levels in serum, hepatic homogenate, and mitochondria. Furthermore, it inhibited the increase of cyclooxygenase (COX)-2 with the regulation of nuclear factor-kappa B (NF-κB) and bcl-2 proteins in the liver, suggesting that the protective potential of Kangenkaryu extract against metabolic syndrome would be attributed to the regulation of COX-2, NF-κB, and bcl-2 signalling pathways. This study indicated that Kangen-karyu extract significantly improved high-fructose-induced metabolic syndrome such as hyperglycaemia, hyperlipidaemia, and hypertension through the reductions of TG and cholesterol contents with the regulation of hepatic SREBP-1 protein and the NF-κB signalling pathway.
Evaluation of the estrogenic activity of the constituents in the fruits of Vitex rotundifolia L. for the potential treatment of premenstrual syndrome
Authors: Hu Yuan , Hou Ting-Ting , Zhang Qiao-Yan , Xin Hai-Liang , Zheng Han-Chen , Qin Lu-Ping , Rahman Khalid 
Published: September 2007

Abstract
The ethanol extract of the fruits of Vitex rotundifolia (VRE) and its four major compounds (casticin, luteolin, rotundifuran and agnuside) were tested for their estrogen-like activity by using the modified cell proliferation assay (E-SCREEN assessment system), as well as the estrogen receptor (ERα), estrogen receptor-regulated progesterone receptor and pS2 mRNA expression in MCF-7 cells. The results showed that only agnuside and rotundifuran could stimulate the proliferation of MCF-7 cells. These actions were dose dependent (range from 100 nm to 10 μm) and could be significantly inhibited by the specific estrogen receptor antagonist ICI 182,780. The estrogen receptor ERα and the estrogen receptor-regulated progesterone receptor and pS2 mRNA levels were increased by treatment with rotundifuran and agnuside within 24 h, and the effects could be reversed by ICI 182,780. The standardization of the extract and constituents were carried out by means of a high-performance liquid chromatography-fingerprint. It was concluded that VRE and its compounds showed estrogen-like activity and that the estrogenic effects of rotundifuran and agnuside were mediated by the estrogen inducible gene, which may be useful in regulating the hormone levels to treat related diseases. However, further studies are required to assess the physiological significance of VRE in animals and man.
A linear mixed-effects statistical model for in-vivo evaluation of recombinant human growth hormone implants in hypophysectomized rats
Authors: Santoveña A , García J T , Fariña J B , Llabrés M 
Published: September 2007

Abstract
We have used a linear mixed-effects statistical model to evaluate previously published results of body weight evolution in hypophysectomized (Hpx) rats after administration of two different controlled-release formulations of recombinant human growth hormone (rhGH). Using the linear mixed-effects model, it was possible to distinguish between maximal pharmacological response with time in different subjects and relate it to the structure of the different formulations, the release of the hormone from them and the time necessary to obtain a quantitative result as a consequence of the hormone activity, contrary to the multivariate variance analysis model (MANOVA) used in our earlier work. These results confirmed that the maximum body weight gain obtained with the controlled-release implants is similar to that with subcutaneous rhGH, but with the advantage that laminar biodegradable implants need to be administered only once every 2 weeks.
Adolescents’ Discussions About Contraception or STDs with Partners Before First Sex
Authors: Ryan Suzanne , Franzetta Kerry , Manlove Jennifer , Holcombe Emily 
Published: September 2007

CONTEXT: Limited research has examined the individual, family and relationship factors that determine whether teenagers discuss contraception or STDs with their sexual partners before having sex for the first time.METHODS: Logistic regression analyses of data from 1,426 teenagers who participated in Waves 1 (1995) and 2 (1996) of the National Longitudinal Study of Adolescent Health and who had first sex between waves examined factors influencing whether respondents discussed contraception or STDs with their partner before first sex, and whether these factors differ by gender.RESULTS: Fifty‐three percent of females and 45% of males discussed contraception or STDs before having first sex. The greater respondents’ perceived condom knowledge and the greater their communication with their parents about everyday life, the higher their odds of discussing contraception or STDs before first sex (odds ratio, 1.2 for each). Being black was positively associated with sexual communication before first sex (1.9); as the number of dating activities and score on a test of verbal ability increased, so did the odds of such communication (1.6 and 1.02, respectively). The predictors of discussions about contraception or STDs did not differ by gender.CONCLUSIONS: By increasing teenagers’ knowledge about condoms and other methods of contraception, pregnancy and STD prevention programs can help to encourage communication among teenage partners before the initiation of sexual intercourse. Programs should also encourage conversations between parents and teenagers, even when not about sex.
California Parents’ Preferences and Beliefs Regarding School‐Based Sex Education Policy
Authors: Constantine Norman A. , Jerman Petra , Huang Alice X. 
Published: September 2007

CONTEXT:  Policy debates over the merits of abstinence‐only versus comprehensive approaches to sex education are ongoing, despite well‐documented public support for comprehensive sex education. Although parents are key stakeholders in the outcomes of these debates, their views have been less thoroughly considered. METHODS:  A random digit dial survey of 1,284 California parents was conducted in 2006. Parents were asked about their sex education policy preferences, the importance of teaching selected topics at different grade levels and reasons for their preferences. Cross‐tabulations and odds ratios were used to assess regional and other subgroup differences. RESULTS:  Overall, 89% of parents reported a preference for comprehensive sex education, and 11% for abstinence‐only education. Support for comprehensive sex education was high in all regions (87–93%) and across all subgroup characteristics: race or ethnicity (79–92%), age (86–94%), education (84–93%), household income (87–92%), religious affiliation (86–91%), religious service attendance (69–96%) and ideological leaning (71–96%). Four types of reasons for preferences emerged: those focused on the consequences of actions, on the importance of providing complete information, on the inevitability of adolescents’ engaging in sex and on religious or purity‐based morality concerns. While 64% of abstinence‐only supporters cited the last type (absolutist reasons), 94% of comprehensive sex education supporters cited one of the first three (pragmatic reasons). CONCLUSIONS:  The high levels of support for comprehensive sex education across California’s diverse regions and demographic subgroups suggest that such support may be generalizable to communities and school districts both in California and around the country. Furthermore, ideological differences might be less important to the sex education debates than the distinction between pragmatic and absolutist perspectives.
Mechanisms of Low-Glucose Sensitivity in Carotid Body Glomus Cells
Authors: García-Fernández María , Ortega-Sáenz Patricia , Castellano Antonio , López-Barneo José 
Published: September 2007

OBJECTIVE—Glucose sensing is essential for the adaptive counterregulatory responses to hypoglycemia. We investigated the mechanisms underlying carotid body (CB) glomus cells activation by low glucose.
RESEARCH DESIGN/METHODS AND RESULTS—Removal of extracellular glucose elicited a cell secretory response, abolished by blockade of plasma membrane Ca2+ channels, and a reversible increase in cytosolic Ca2+ concentration. These data indicated that glucopenia induces transmembrane Ca2+ influx and transmitter secretion. In patch-clamped glomus cells, exposure to low glucose resulted in inhibition of macroscopic outward K+ currents and in the generation of a depolarizing receptor potential (DRP). The DRP was abolished upon removal of extracellular Na+. The membrane-permeable 1-oleoyl-2-acetyl-sn-glycerol induced inward currents of similar characteristics as the current triggered by glucose deficiency. The functional and pharmacological analyses suggest that low glucose activates background cationic Na+-permeant channels, possibly of the transient receptor potential C subtype. Rotenone, a drug that occludes glomus cell sensitivity to hypoxia, did not abolish responsiveness to low glucose. The association of Glut2 and glucokinase, characteristic of some high glucose–sensing cells, did not seem to be needed for low glucose detection.
CONCLUSIONS—Altogether, these data support the view that the CB is a multimodal chemoreceptor with a physiological role in glucose homeostasis.