bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulatory T Cells Are Locally Induced during Intravaginal Infection of Mice withNeisseria gonorrhoeae
Authors: Imarai Mónica , Candia Enzo , Rodriguez-Tirado Carolina , Tognarelli Javier , Pardo Mirka , Pérez Tomas , Valdés Daniel , Reyes-Cerpa Sebastián , Nelson Pablo , Acuna-Castillo Claudio , Maisey Kevin 
Published: September 2008

ABSTRACTNeisseria gonorrhoeaeis a gram-negative diplococcus that in human beings produces gonorrhea. Much clinical evidence has led to the conclusion that gonococcus has important mechanisms to evade host immune functions; however, these mechanisms are only now beginning to be elucidated. In this study, we determined that the BALB/c mouse is a good animal model to study gonococcus infection and examined the immune response against the bacteria. We determined that after intravaginal inoculation of mice withNeisseria gonorrhoeae, the bacteria reached and invaded the upper female reproductive tissues and elicited a T-cell-specific immune response associated with a very weak humoral response, altogether resembling gonococcus infection and disease in women. Remarkably, in the draining lymph nodes of the genital tracts of infected mice, we found an increase of regulatory T lymphocytes, namely, transforming growth factor β1-positive CD4+T cells and CD4+CD25+Foxp3+T cells. Altogether, results indicate thatN. gonorrhoeaeinduces regulatory T cells, which might be related to the local survival of the pathogen and the establishment of a chronic asymptomatic infection.
Experimental Malaria Infection Triggers Early Expansion of Natural Killer Cells
Authors: Kim Charles C. , Parikh Sunil , Sun Joseph C. , Myrick Alissa , Lanier Lewis L. , Rosenthal Philip J. , DeRisi Joseph L. 
Published: September 2008

ABSTRACTIn order to gain a better understanding of gene expression during early malaria infection, we conducted microarray analysis of early blood responses in mice infected with erythrocytic-stagePlasmodium chabaudi. Immediately following infection, we observed coordinated and sequential waves of immune responses, with interferon-associated gene transcripts dominating by 16 h postinfection, followed by strong increases in natural killer (NK) cell-associated and major histocompatibility complex class I-related transcripts by 32 h postinfection. We showed by flow cytometry that the observed elevation in NK cell-associated transcripts was the result of a dramatic increase in the proportion of NK cells in the blood during infection. Subsequent microarray analysis of NK cells isolated from the peripheral blood of infected mice revealed a cell proliferation expression signature consistent with the observation that NK cells replicate in response to infection. Early proliferation of NK cells was directly observed in studies with adoptively transferred cells in infected mice. These data indicate that the early response toP. chabaudiinfection of the blood is marked by a primary wave of interferon with a subsequent response by NK cells.
Comparing biomass and nutrient removals of stems and fresh and predried whole trees in thinnings in two Norway spruce experiments
Authors: Stupak Inge , Nordfjell Tomas , Gundersen Per 
Published: September 2008

In Denmark, thinning trees used for energy purposes are cut and left to dry in the stand before they are removed as whole trees. This practice causes shedding of needles and reduces nutrient removals for the benefit of long-term site fertility. It is uncertain, however, to what extent needles are shed and actual nutrient loss is affected by this practice. To address this question, we compared biomass and nutrient removals in two Norway spruce ( Picea abies (L.) Karst) experiments in western Denmark. Three contemporary thinning harvest intensities were examined: harvesting of fresh whole trees, predried whole trees, and stems only. The whole trees were chipped individually, and samples were removed to determine moisture and nutrient contents, whereas sample discs were removed from harvested stems. The biomass content of the cut whole trees was estimated to decrease 17% during predrying, whereas nutrient contents decreased 35%–60% for N, P, and K and <32% for Ca and Mg. The biomass content of stems was estimated to be 35%–42% lower than that of fresh whole trees. The corresponding differences in nutrient contents were in the range 84%–89% for N, P, and K and 73%–80% for Ca and Mg. Predrying and technological methods to reduce nutrient removals were compared and discussed.
Climate Impacts of Making Evapotranspiration in the Community Land Model (CLM3) Consistent with the Simple Biosphere Model (SiB)
Authors: Lawrence Peter J. , Chase Thomas N. 
Published: September 2008

Abstract
In recent climate sensitivity experiments with the Community Climate System Model, version 3 (CCSM3), a wide range of studies have found that the Community Land Model, version 3 (CLM3), simulates mean global evapotranspiration with low contributions from transpiration (15%), and high contributions from soil and canopy evaporation (47% and 38%, respectively). This evapotranspiration partitioning is inconsistent with the consensus of other land surface models used in GCMs. To understand the high soil and canopy evaporation and the low transpiration observed in the CLM3, select individual components of the land surface parameterizations that control transpiration, canopy and soil evaporation, and soil hydrology are compared against the equivalent parameterizations used in the Simple Biosphere Model, versions 2 and 3 (SiB2 and SiB3), and against more recent developments with CLM. The findings of these investigations are used to develop new parameterizations for CLM3 that would reproduce the functional dynamics of land surface processes found in SiB and other alternative land surface parameterizations. Global climate sensitivity experiments are performed with the new land surface parameterizations to assess how the new SiB, consistent CLM land surface parameterizations, influence the surface energy balance, hydrology, and atmospheric fluxes in CLM3, and through that the larger-scale climate modeled in CCSM3. It is found that the new parameterizations enable CLM to simulate evapotranspiration partitioning consistently with the multimodel average of other land surface models used in GCMs, as evaluated by Dirmeyer et al. (2005). The changes in surface fluxes also resulted in a number of improvements in the simulation of precipitation and near-surface air temperature in CCSM3. The new model is fully coupled in the CCSM3 framework, allowing a wide range of climate modeling investigations without the surface hydrology issues found in the current CLM3 model. This provides a substantially more robust framework for performing climate modeling experiments investigating the influence of land cover change and surface hydrology in CLM and CCSM than the existing CLM3 parameterizations. The study also shows that changes in land surface hydrology have global scale impacts on model climatology.
Interaction of Typhoon Shanshan (2006) with the Midlatitude Trough from both Adjoint-Derived Sensitivity Steering Vector and Potential Vorticity Perspectives
Authors: Wu Chun-Chieh , Chen Shin-Gan , Chen Jan-Huey , Chou Kun-Hsuan , Lin Po-Hsiung 
Published: September 2008

Abstract
Targeted observation is one of the most important research and forecasting issues for improving tropical cyclone predictability. A new parameter [i.e., the adjoint-derived sensitivity steering vector (ADSSV)] has been proposed and adopted as one of the targeted observing strategies in the Dropwindsonde Observations for Typhoon Surveillance near the Taiwan Region (DOTSTAR). The ADSSV identifies the sensitive areas at the observing time to the steering flow at the verifying time through the adjoint calculation. In this study, the ADSSV is calculated from the nonlinear forecast model of the fifth-generation Pennsylvania State University–National Center for Atmospheric Research (PSU–NCAR) Mesoscale Model (MM5) and its adjoint to interpret the dynamical processes in the interaction between Typhoon Shanshan (2006) and the midlatitude trough. The ADSSV results imply that high-sensitivity regions affecting the motion of Typhoon Shanshan are located at the edge of the subtropical high and the 500-hPa midlatitude trough over northern central China. These ADSSV signals are in very good agreement with the quantitative evaluation based on the potential vorticity (PV) diagnosis. The vertical structure of the ADSSV is also shown for more physical insights into the typhoon–trough interaction. The maximum ADSSV occurs at 800–500 hPa to the southeast of Shanshan (associated with the subtropical high), while distinct ADSSV signals are located upstream of the storm center at about 500–300 hPa (associated with the mid- to upper-tropospheric midlatitude trough). Overall, it is demonstrated that the ADSSV features can well capture the signal of the large-scale trough feature affecting the motion of Shanshan, which can also be well validated from the PV analysis.
Androgen depletion increases the efficacy of bone marrow transplantation in ameliorating experimental autoimmune encephalomyelitis
Authors: Barnard Adele L. , Chidgey Ann P. , Bernard Claude C. , Boyd Richard L. 
Published: September 2008

AbstractBone marrow transplantation (BMT) potentially represents a novel therapy for the amelioration and even cure for multiple sclerosis (MS). It has important advantages over immunosuppressive drug treatments because, while effecting broad-based ablation of the immune system and autoreactive cells, it provides an important means for overcoming the resultant immunodeficiency, while possibly restoring self-tolerance. However, both of these benefits are predicated on a functional thymus that undergoes profound age-induced atrophy from puberty. Reversal of thymic atrophy has been achieved by several procedures, including removal of sex steroids by surgical or chemical (LHRH agonist) castration. Using a murine model of MS, experimental autoimmune encephalomyelitis (EAE), we combined BMT with androgen depletion to induce immune regeneration, and investigated the kinetics of increased thymic function on immune reconstitution and disease reduction. We show that androgen depletion significantly increased the efficacy of BMT to ameliorate the clinical signs of EAE while concurrently restoring the periphery with increased naive and regulatory lymphocytic populations. Upon rechallenge, mice with a regenerated thymus had a slower onset of clinical symptoms compared with mice undergoing BMT only. These results suggest that thymic regeneration strategies may be used as a complement to conventional BMT protocols for the treatment of MS.
Cross-species comparison of biological themes and underlying genes on a global gene expression scale in a mouse model of colorectal liver metastasis and in clinical specimens
Authors: Bandapalli Obul Reddy , Kahlert Christoph , Hellstern Victoria , Galindo Luis , Schirmacher Peter , Weitz Jürgen , Brand Karsten 
Published: September 2008

Abstract

Background
Invasion-related genes over-expressed by tumor cells as well as by reacting host cells represent promising drug targets for anti-cancer therapy. Such candidate genes need to be validated in appropriate animal models.

Results
This study examined the suitability of a murine model (CT26/Balb/C) of colorectal liver metastasis to represent clinical liver metastasis specimens using a global gene expression approach. Cross-species similarity was examined between pure liver, liver invasion, tumor invasion and pure tumor compartments through overlap of up-regulated genes and gene ontology (GO)-based biological themes on the level of single GO-terms and of condensed GO-term families. Three out of four GO-term families were conserved in a compartment-specific way between the species: secondary metabolism (liver), invasion (invasion front), and immune response (invasion front and liver). Among the individual GO-terms over-represented in the invasion compartments in both species were "extracellular matrix", "cell motility", "cell adhesion" and "antigen presentation" indicating that typical invasion related processes are operating in both species. This was reflected on the single gene level as well, as cross-species overlap of potential target genes over-expressed in the combined invasion front compartments reached up to 36.5%.
Generally, histopathology and gene expression correlated well as the highest single gene overlap was found to be 44% in syn-compartmental comparisons (liver versus liver) whereas cross-compartmental overlaps were much lower (e.g. liver versus tumor: 9.7%). However, single gene overlap was surprisingly high in some cross-compartmental comparisons (e.g. human liver invasion compartment and murine tumor invasion compartment: 9.0%) despite little histolopathologic similarity indicating that invasion relevant genes are not necessarily confined to histologically defined compartments.

Conclusion
In summary, cross-species comparison on a global gene expression scale suggests the validity of an animal model representing the human situation. The actual yield of potential target genes depends on several variables including the animal model, choice of inclusion criteria, inherent species differences and histologic assessment.
The stress responsive and morphologically regulated hsp90 gene from Paracoccidioides brasiliensis is essential to cell viability
Authors: Nicola André M , Andrade Rosângela V , Dantas Alessandra S , Andrade Patrícia A , Arraes Fabrício BM , Fernandes Larissa , Silva-Pereira Ildinete , Felipe Maria Sueli S 
Published: September 2008

Abstract

Background

Paracoccidioides brasiliensis is a dimorphic fungus that causes the most prevalent systemic mycosis in Latin America. The response to heat shock is involved in pathogenesis, as this pathogen switches from mycelium to yeast forms in a temperature dependent fashion that is essential to establish infection. HSP90 is a molecular chaperone that helps in the folding and stabilization of selected polypeptides. HSP90 family members have been shown to present important roles in fungi, especially in the pathogenic species, as an immunodominant antigen and also as a potential antifungal therapeutic target.

Results
In this work, we decided to further study the Pbhsp90 gene, its expression and role in cell viability because it plays important roles in fungal physiology and pathogenesis. Thus, we have sequenced a Pbhsp90 cDNA and shown that this gene is present on the genome as a single copy. We have also confirmed its preferential expression in the yeast phase and its overexpression during dimorphic transition and oxidative stress. Treatment of the yeast with the specific HSP90 inhibitors geldanamycin and radicicol inhibited growth at 2 and 10 μM, respectively.

Conclusion
The data confirm that the Pbhsp90 gene encodes a morphologically regulated and stress-responsive protein whose function is essential to cell viability of this pathogen. This work also enforces the potential of HSP90 as a target for antifungal therapies, since the use of HSP90 inhibitors is lethal to the P. brasiliensis yeast cells in a dose-responsive manner.
Decrease in excitatory neurons, astrocytes and proliferating progenitors in the cerebral cortex of mice lacking exon 3 from the Fgf2 gene
Authors: Chen Kesi , Ohkubo Yasushi , Shin Dana , Doetschman Thomas , Sanford L Philip , Li Hongqi , Vaccarino Flora M 
Published: September 2008

Abstract

Background
The Fgf2 gene is expressed in the brain neuroepithelium during embryonic development and in astroglial cells throughout life. Previous knockout studies suggested that FGF2 plays a role in the proliferation of neural progenitors in the embryonic cerebral cortex. These studies exclusively used knockout alleles lacking the Fgf2 exon 1. However, the description of putative alternative exons located downstream from the canonical exon 1 raised the possibility that alternatively spliced transcripts may compensate for the lack of the canonical exon 1 in the Fgf2 -/- mice.

Results
We generated and characterized a new line of Fgf2 knockout mice lacking the expression of exon 3, which is conserved in all Fgf2 transcripts and contains essential heparin and receptor binding interfaces. The expression of Fgf2 exon 3 was prevented by inserting a transcriptional STOP cassette in the Fgf2 genomic locus. These mice demonstrate a phenotype in the adult neocortex characterized by decreased density and number of cortical excitatory neurons and astrocytes, which is virtually identical to that of the Fgf2 -/- mice lacking exon 1. In addition, we also show that the Fgf2 exon 3 knockout mice have decreased proliferation of precursors in the adult cerebral cortex, which had not been previously investigated in the other mutant lines.

Conclusion
The results demonstrate that the phenotype of two completely different Fgf2 KO mouse lines, lacking exon 1 or exon 3, is remarkably similar. The combined results from these KO models clearly indicate that FGF2 plays a role in cortical cell genesis during embryonic development as well as in adulthood. Thus, FGF2 may be required for the maintenance of the pool of adult cortical progenitor cells.
NPHS2variation in focal and segmental glomerulosclerosis
Authors: Tonna Stephen J , Needham Alexander , Polu Krishna , Uscinski Andrea , Appel Gerald B , Falk Ronald J , Katz Avi , Al-Waheeb Salah , Kaplan Bernard S , Jerums George , Savige Judy , Harmon Jennifer , Zhang Kang , Curhan Gary C , Pollak Martin R 
Published: September 2008

Abstract

Background
Focal and segmental glomerulosclerosis (FSGS) is the most common histologic pattern of renal injury seen in adults with idiopathic proteinuria. Homozygous or compound heterozygous mutations in the podocin gene NPHS2 are found in 10–30% of pediatric cases of steroid resistant nephrosis and/or FSGS.

Methods
We studied the spectrum of genetic variation in 371 individuals with predominantly late onset FSGS (mean age of onset 25 years) by analysis of DNA samples.

Results
We identified 15 non-synonymous alleles that changed the amino acid sequence in 63 of the subjects screened (17%). Eight of these (p.R138Q, p.V180M, p.R229Q, p.E237Q, p.A242V, p.A284V, p.L327F and the frameshift 855–856 delAA) are alleles previously reported to cause FSGS in either the homozygous or compound heterozygous states, while the remaining 7 (p.R10T, p.V127W, p.Q215X, p.T232I, p.L270F, p.L312V and the frameshift 397delA) are novel alleles that have not been demonstrated previously. Twelve individuals of the 371 (3.2%) screened had two likely disease-causing NPHS2 alleles, present in either a homozygous or compound heterozygous state. We genotyped the two most common of the non-synonymous NPHS2 alleles (p.A242V and p.R229Q) identified by resequencing in participants from the Nurses' Health Study and also genotyped p.R229Q in 3 diabetic cohorts. We found that the presence of either of these variants does not significantly alter the risk of albuminuria in the Nurses' Health participants, nor does p.R229Q associate with "diabetic nephropathy".

Conclusion

NPHS2 mutations are a rare cause of FSGS in adults. The most common non-synonymous NPHS2 variants, p.R229Q and p.A242V, do not appear to alter the risk of proteinuria in the general population nor does p.R229Q associate with measures of kidney dysfunction in diabetic individuals. Our results help clarify the frequency of FSGS-causing NPHS2 mutations in adults and broaden our understanding of the spectrum of NPHS2 mutations that lead to human disease.
The effects of timing of fine needle aspiration biopsies on gene expression profiles in breast cancers
Authors: Wong Vietty , Wang Dong-Yu , Warren Keisha , Kulkarni Supriya , Boerner Scott , Done Susan Jane , Leong Wey Liang 
Published: September 2008

Abstract

Background
DNA microarray analysis has great potential to become an important clinical tool to individualize prognostication and treatment for breast cancer patients. However, with any emerging technology, there are many variables one must consider before bringing the technology to the bedside. There are already concerted efforts to standardize protocols and to improve reproducibility of DNA microarray. Our study examines one variable that is often overlooked, the timing of tissue acquisition, which may have a significant impact on the outcomes of DNA microarray analyses especially in studies that compare microarray data based on biospecimens taken in vivo and ex vivo.

Methods
From 16 patients, we obtained paired fine needle aspiration biopsies (FNABs) of breast cancers taken before (PRE) and after (POST) their surgeries and compared the microarray data to determine the genes that were differentially expressed between the FNABs taken at the two time points. qRT-PCR was used to validate our findings. To examine effects of longer exposure to hypoxia on gene expression, we also compared the gene expression profiles of 10 breast cancers from clinical tissue bank.

Results
Using hierarchical clustering analysis, 12 genes were found to be differentially expressed between the FNABs taken before and after surgical removal. Remarkably, most of the genes were linked to FOS in an early hypoxia pathway. The gene expression of FOS also increased with longer exposure to hypoxia.

Conclusion
Our study demonstrated that the timing of fine needle aspiration biopsies can be a confounding factor in microarray data analyses in breast cancer. We have shown that FOS-related genes, which have been implicated in early hypoxia as well as the development of breast cancers, were differentially expressed before and after surgery. Therefore, it is important that future studies take timing of tissue acquisition into account.
The role of antioxidant supplement in immune system, neoplastic, and neurodegenerative disorders: a point of view for an assessment of the risk/benefit profile
Authors: Brambilla Daria , Mancuso Cesare , Scuderi Mariagrazia Rita , Bosco Paolo , Cantarella Giuseppina , Lempereur Laurence , Di Benedetto Giulia , Pezzino Salvatore , Bernardini Renato 
Published: September 2008

AbstractThis review will discuss some issues related to the risk/benefit profile of the use of dietary antioxidants. Thus, recent progress regarding the potential benefit of dietary antioxidants in the treatment of chronic diseases with a special focus on immune system and neurodegenerative disorders will be discussed here. It is well established that reactive oxygen species (ROS) play an important role in the etiology of numerous diseases, such as atherosclerosis, diabetes and cancer. Among the physiological defense system of the cell, the relevance of antioxidant molecules, such as glutathione and vitamins is quite well established. Recently, the interest of researchers has, for example, been conveyed on antioxidant enzyme systems, such as the heme oxygenase/biliverdin reductase system, which appears modulated by dietary antioxidant molecules, including polyphenols and beta-carotene. These systems possibly counteract oxidative damage very efficiently and finally modulate the activity of oxidative phenomena occurring, for instance, during pathophysiological processes. Although evidence shows that antioxidant treatment results in cytoprotection, the potential clinical benefit deriving from both nutritional and supplemental antioxidants is still under wide debate. In this line, the inappropriate assumption of some lipophylic vitamins has been associated with increased incidence of cancer rather than with beneficial effects.