bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Private Parts of Animals: Aristotle on the Teleology of Sexual Difference
Authors: Nielsen Karen 
Published: September 2008

AbstractIn this paper I examine Aristotle's account of sexual difference in Generation of Animals, arguing that Aristotle conceives of the production of males as the result of a successful teleological process, while he sees the production of females as due to material forces that defeat the norms of nature. My suggestion is that Aristotle endorses what I call the "degrees of perfection" model. I challenge Devin Henry's attempt to argue that Aristotle explains sex determination exclusively with reference to material necessity (in particular, levels of "vital heat" in the male semen), for Aristotle's notion of "sufficient" or "deficient" vital heat is itself teleological. If, as Aristotle is aware, male and female embryos appear with approximately equal frequency in most species, how, in light of Physics II, can he conceive of the former as in accordance with nature, and the latter as somehow contrary to nature? My proposal is that Aristotle's notion of what happens usually (ως επì τò πoλυ) is bifurcated: the usual need not be more frequent.
Simulating Range Oversampled Doppler Radar Profiles of Inhomogeneous Targets
Authors: Schutgens N. A. J. 
Published: September 2008

Abstract
A new technique for generating range oversampled profiles of Doppler radar signals that have been backscattered by distributed targets is presented in this paper. The technique was developed for spaceborne cloud radars, but it can just as well be used for ground-based precipitation or wind-profiling radars. The technique is more versatile than the traditional inverse FFT technique and faster than the individual hydrometeor simulation (Monte Carlo) technique.
Doppler radar signals from backscattering hydrometeors are essentially correlated stochastic variables. The technique uses an accurate description of covariances between voltages measured for different pulses and at different positions (range gates) along a profile. A matrix formalism is developed to subsequently transform uncorrelated Gaussian noise into correlated receiver voltages with the appropriate covariances.
In particular, the new technique deals with target variability in a physically consistent manner, accounting for the effects of inhomogeneity both within the instantaneous field of view and between subsequent pulses. The new technique is showcased with examples of simulated 95-GHz Doppler radar observations by the Earth Clouds, Aerosols and Radiation Explorer (EarthCARE) space mission.
IRF8 regulates B-cell lineage specification, commitment, and differentiation
Authors: Wang Hongsheng , Lee Chang Hoon , Qi Chenfeng , Tailor Prafullakumar , Feng Jianxun , Abbasi Sadia , Atsumi Toru , Morse Herbert C. 
Published: September 2008

AbstractPU.1, IKAROS, E2A, EBF, and PAX5 comprise a transcriptional network that orchestrates B-cell lineage specification, commitment, and differentiation. Here we identify interferon regulatory factor 8 (IRF8) as another component of this complex, and show that it also modulates lineage choice by hematopoietic stem cells (HSCs). IRF8 binds directly to an IRF8/Ets consensus sequence located in promoter regions of Sfpi1 and Ebf1, which encode PU.1 and EBF, respectively, and is associated with transcriptional repression of Sfpi1 and transcriptional activation of Ebf1. Bone marrows of IRF8 knockout mice (IRF8−/−) had significantly reduced numbers of pre-pro-B cells and increased numbers of myeloid cells. Although HSCs of IRF8−/− mice failed to differentiate to B220+ B-lineage cells in vitro, the defect could be rescued by transfecting HSCs with wild-type but not with a signaling-deficient IRF8 mutant. In contrast, overexpression of IRF8 in HSC-differentiated progenitor cells resulted in growth inhibition and apoptosis. We also found that IRF8 was expressed at higher levels in pre-pro-B cells than more mature B cells in wild-type mice. Together, these results indicate that IRF8 modulates lineage choice by HSCs and is part of the transcriptional network governing B-cell lineage specification, commitment, and differentiation.
Down-regulation of the forkhead transcription factor Foxp1 is required for monocyte differentiation and macrophage function
Authors: Shi Can , Sakuma Masashi , Mooroka Toshifumi , Liscoe Alison , Gao Huiyun , Croce Kevin J. , Sharma Arjun , Kaplan David , Greaves David R. , Wang Yunmei , Simon Daniel I. 
Published: September 2008

AbstractDown-regulation of the forkhead transcription factor Foxp1 by integrin engagement controls monocyte differentiation in vitro. To determine whether Foxp1 plays a critical role in monocyte differentiation and macrophage functions in vivo, we generated transgenic mice (macFoxp1tg) overexpressing human FOXP1 in monocyte/macrophage lineage cells using the CD68 promoter. Circulating blood monocytes from macFoxp1tg mice have reduced expression of the receptor for macrophage colony-stimulating factor (c-Fms/M-CSFR), impaired migratory capacity, and diminished accumulation as splenic macrophages. Macrophage functions, including cytokine production, phagocytosis, and respiratory burst were globally impaired in macFoxp1tg compared with wild-type cells. Osteoclastogenesis and bone resorption activity were also attenuated in macFoxp1tg mice. In models of chemical and bacterial peritonitis, macFoxp1tg mice exhibited reduced macrophage accumulation, bacterial clearance, and survival. Enforced overexpression of c-Fms/M-CSFR reversed the cytokine production and phagocytosis defects in macFoxp1tg macrophages, indicating that repression of c-fms/M-CSFR is likely the dominant mechanism responsible for Foxp1 action in monocyte differentiation and macrophage function. Taken together, these observations identify down-regulation of Foxp1 as critical for monocyte differentiation and macrophage functions in vivo.
Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study
Authors: Salles Gilles , Mounier Nicolas , de Guibert Sophie , Morschhauser Franck , Doyen Chantal , Rossi Jean-François , Haioun Corinne , Brice Pauline , Mahé Béatrice , Bouabdallah Reda , Audhuy Bruno , Ferme Christophe , Dartigeas Caroline , Feugier Pierre , Sebban Catherine , Xerri Luc , Foussard Charles 
Published: September 2008

Abstract
The FL2000 study was undertaken to evaluate the combination of the anti-CD20 monoclonal antibody rituximab with chemotherapy plus interferon in the first-line treatment of follicular lymphoma patients with a high tumor burden. Patients were randomly assigned to receive either 12 courses of the chemotherapy regimen CHVP (cyclophosphamide, adriamycin, etoposide, and prednisolone) plus interferon-α2a (CHVP+I arm) over 18 months or 6 courses of the same chemotherapy regimen combined with 6 infusions of 375 mg/m2 rituximab and interferon for the same time period (R-CHVP+I arm). After a median follow-up of 5 years, event-free survival estimates were, respectively, 37% (95% confidence interval [CI], 29%-44%) and 53% (95% CI, 45%-60%) in the CHVP+I and R-CHVP+I arm (P = .001). Five-year overall survival estimates were not statistically different in the CHVP+I (79%; 95% CI, 72%-84%) and R-CHVP+I (84%; 95% CI, 78%-84%) arms. In a multivariate regression analysis, event-free survival was significantly influenced by both the Follicular Lymphoma International Prognostic Index score (hazard ratio = 2.08; 95% CI, 1.6%-2.8%) and the treatment arm (hazard ratio = 0.59; 95% CI, 0.44%-0.78%). With a 5-year follow-up, the combination of rituximab with CHVP+I provides superior disease control in follicular lymphoma patients despite a shorter duration of chemotherapy. This study's clinical trial was registered at the National Institutes of Health website as no. NCT00136552.
FoxO3a regulates hematopoietic homeostasis through a negative feedback pathway in conditions of stress or aging
Authors: Miyamoto Kana , Miyamoto Takeshi , Kato Reiko , Yoshimura Akihiko , Motoyama Noboru , Suda Toshio 
Published: September 2008

Abstract
Stress or aging of tissue-specific stem cells is considered central to the decline of tissue homeostasis in the elderly, although little is known of molecular mechanisms underlying hematopoietic stem cell (HSC) aging and stress resistance. Here, we report that mice lacking the transcription factor forkhead box O3a (FoxO3a) develop neutrophilia associated with inhibition of the up-regulation of negative regulator of cell proliferation, Sprouty-related Ena/VASP homology 1 domain-containing proteins 2 (Spred2) and AKT and ERK activation, in HSCs during hematopoietic recovery following myelosuppressive stress conditions. Compared with aged wild-type mice, more severe neutrophilia was also observed in aged Foxo3a-deficient mice. AKT and ERK activation and inhibition of Spred2 were detected in HSCs from aged FoxO3a-deficient mice. Spred2-deficient mice also developed neutrophilia during hematopoietic recovery following myelosuppressive stress, indicating that FoxO3a plays a pivotal role in maintenance, integrity, and stress resistance of HSCs through negative feedback pathways for proliferation. This will provide new insight into the hematopoietic homeostasis in conditions of aging and stress.
CX3CL1/fractalkine is released from apoptotic lymphocytes to stimulate macrophage chemotaxis
Authors: Truman Lucy A. , Ford Catriona A. , Pasikowska Marta , Pound John D. , Wilkinson Sarah J. , Dumitriu Ingrid E. , Melville Lynsey , Melrose Lauren A. , Ogden Carol Anne , Nibbs Robert , Graham Gerard , Combadiere Christophe , Gregory Christopher D. 
Published: September 2008

AbstractCells undergoing apoptosis are efficiently located and engulfed by phagocytes. The mechanisms by which macrophages, the professional scavenging phagocytes of apoptotic cells, are attracted to sites of apoptosis are poorly defined. Here we show that CX3CL1/fractalkine, a chemokine and intercellular adhesion molecule, is released rapidly from apoptotic lymphocytes, via caspase- and Bcl-2-regulated mechanisms, to attract macrophages. Effective chemotaxis of macrophages to apoptotic lymphocytes is dependent on macrophage fractalkine receptor, CX3CR1. CX3CR1 deficiency caused diminished recruitment of macrophages to germinal centers of lymphoid follicles, sites of high-rate B-cell apoptosis. These results provide the first demonstration of chemokine/chemokine-receptor activity in the navigation of macrophages toward apoptotic cells and identify a mechanism by which macrophage infiltration of tissues containing apoptotic lymphocytes is achieved.
Essential role of Rap signal in pre-TCR–mediated β-selection checkpoint in αβ T-cell development
Authors: Kometani Kohei , Moriyama Masaki , Nakashima Yasuhiro , Katayama Yoshinori , Wang Shu-Fang , Yamasaki Sho , Saito Takashi , Hattori Masakazu , Minato Nagahiro 
Published: September 2008

Abstract
We demonstrate that lck promoter–driven conditional expression of transgenic SPA-1, a Rap GTPase-activation protein, causes a profound defect of αβ T-cell development at the CD4/CD8 double-negative (DN) stage due to enhanced cell death without affecting γδ T-cell development. The effect was specific to the DN stage, because CD4 promoter–driven SPA-1 expression hardly affected T-cell development. Rap1A17, a dominant-negative Rap mutant, interfered with the generation of double-positive (DP) cells from Rag2−/− fetal thymocytes in vitro in the presence of anti-CD3ϵ antibody and Notch ligand. Rap GTPases were activated in a DN cell line by the expression of self-oligomerizing CD3 (CD8:CD3ϵ chimera), which substituted autonomous pre–T-cell receptor (TCR) signal, inducing CD69 expression and CD25 down-regulation. Reciprocally, expression of C3G, a Rap guanine nucleotide exchange factor, in both normal and Rag2−/− DN cells markedly enhanced Notch-dependent generation and expansion of DP cells without additional anti-CD3ϵ antibody, thus bypassing pre-TCR. Defective αβ T-cell development in the conditional SPA-1–transgenic mice was restored completely by introducing a p53−/− mutation. These results suggest that endogenous Rap GTPases downstream of pre-TCR play an essential role in rescuing pre-T cells from the p53-mediated checkpoint response, thus allowing Notch-mediated expansion and differentiation.
Adoptive transfer of allogeneic tumor-specific T cells mediates effective regression of large tumors across major histocompatibility barriers
Authors: Boni Andrea , Muranski Pawel , Cassard Lydie , Wrzesinski Claudia , Paulos Chrystal M. , Palmer Douglas C. , Gattinoni Luca , Hinrichs Christian S. , Chan Chi-Chao , Rosenberg Steven A. , Restifo Nicholas P. 
Published: September 2008

AbstractGraft-versus-tumor effects can be achieved after allogeneic bone marrow transplantation in patients with malignancies of the kidney or hematopoietic system but are often accompanied by severe graft-versus-host-disease (GVHD). We sought to maximize graft-versus-tumor while minimizing GVHD using tumor-specific allogeneic effector T cells rather than open-repertoire T cells. We transferred allogeneic CD8+ pmel-1 or CD4+ TRP-1 T cells specific for the melanoma-associated antigens, glycoprotein 100 (gp100) and tyrosinase-related protein-1 (TRP-1), respectively, into B16-melanoma–bearing mice. Mice receiving a preparative regimen of nonmyeloablating (5 Gy) total body irradiation experienced the rapid rejection of tumor-specific allogeneic lymphocytes with no impact on tumor growth. However, when mice were given more intense total body irradiation conditioning regimens combined with autologous bone marrow transplantation, adoptively transferred allogeneic tumor-specific T lymphocytes persisted at detectable levels for several weeks and mediated significant regression of large, vascularized tumors. We found that the risk of GVHD was low when tumor-specific T cells were transferred and significant toxicity was observed only when substantial numbers of open repertoire allogeneic naive T cells were mixed with the tumor-specific lymphocytes. Taken together, these data indicate that the use of tumor-specific allogeneic CD8+ T cells or CD4+ can result in significant antitumor effects in the absence of measurable GVHD.
Tele-assistance in chronic respiratory failure patients: a randomised clinical trial
Authors: Vitacca M. , Bianchi L. , Guerra A. , Fracchia C. , Spanevello A. , Balbi B. , Scalvini S. 
Published: September 2008

Chronic respiratory patients requiring oxygen or home mechanical ventilation experience frequent exacerbations and hospitalisations with related costs. Strict monitoring and care have been recommended. The aim of the present study was to primarily evaluate reduction in hospitalisations and, secondly, exacerbations, general practitioner (GP) calls and related cost-effectiveness of tele-assistance (TA) for these patients.A total of 240 patients (101 with chronic obstructive pulmonary disease (COPD)) were randomised to two groups: an intervention group entered a 1-yr TA programme while controls received traditional care.No anthropometric and clinical differences were found between groups both in baseline and in mortality (18% for TA, 23% for controls). Compared with controls, the TA group experienced significantly fewer hospitalisations (-36%), urgent GP calls (-65%) and acute exacerbations (-71%). Only COPD patients, as a separate group, had fewer hospitalisations, emergency room admissions, urgent GP calls or exacerbations. Each patient referred to staff a mean±sd36±25 times. After deduction of TA costs, the average overall cost for each patient was 33% less than that for usual care.In chronic respiratory failure patients on oxygen or home mechanical ventilation, a nurse-centred tele-assistance prevents hospitalisations while it is cost-effective. The chronic obstructive pulmonary disease group seems to have a greater advantage from tele-assistance.
SQUAT: A web tool to mine human, murine and avian SAGE data
Authors: Leyritz Johan , Schicklin Stéphane , Blachon Sylvain , Keime Céline , Robardet Céline , Boulicaut Jean-François , Besson Jérémy , Pensa Ruggero G , Gandrillon Olivier 
Published: September 2008

AbstractBackgroundThere is an increasing need in transcriptome research for gene expression data and pattern warehouses. It is of importance to integrate in these warehouses both raw transcriptomic data, as well as some properties encoded in these data, like local patterns.DescriptionWe have developed an application called SQUAT (SAGE Querying and Analysis Tools) which is available at:http://bsmc.insa-lyon.fr/squat/. This database gives access to both raw SAGE data and patterns mined from these data, for three species (human, mouse and chicken). This database allows to make simple queries like "In which biological situations is my favorite gene expressed?" as well as much more complex queries like: ≪what are the genes that are frequently co-over-expressed with my gene of interest in given biological situations?≫. Connections with external web databases enrich biological interpretations, and enable sophisticated queries. To illustrate the power of SQUAT, we show and analyze the results of three different queries, one of which led to a biological hypothesis that was experimentally validated.ConclusionSQUAT is a user-friendly information retrieval platform, which aims at bringing some of the state-of-the-art mining tools to biologists.
Onset of meiosis in the chicken embryo; evidence of a role for retinoic acid
Authors: Smith Craig A , Roeszler Kelly N , Bowles Josephine , Koopman Peter , Sinclair Andrew H 
Published: September 2008

Abstract
Background
Meiosis in higher vertebrates shows a dramatic sexual dimorphism: germ cells enter meiosis and arrest at prophase I during embryogenesis in females, whereas in males they enter mitotic arrest during embryogenesis and enter meiosis only after birth. Here we report the molecular analysis of meiosis onset in the chicken model and provide evidence for conserved regulation by retinoic acid.

Results
Meiosis in the chicken embryo is initiated late in embryogenesis (day 15.5), relative to gonadal sex differentiation (from day 6). Meiotic germ cells are first detectable only in female gonads from day 15.5, correlating with the expression of the meiosis marker, SCP3. Gonads isolated from day 10.5 female embryos and grown in serum-free medium could still initiate meiosis at day 16.5, suggesting that this process is controlled by an endogenous clock in the germ cells themselves, and/or that germ cells are already committed to meiosis at the time of explantation. Early commitment is supported by the analysis of chicken STRA8, a pre-meiotic marker shown to be essential for meiosis in mouse. Chicken STRA8 is expressed female-specifically from embryonic day 12.5, preceding morphological evidence of meiosis at day 15.5. Previous studies have shown that, in the mouse embryo, female-specific induction of STRA8 and meiosis are triggered by retinoic acid. A comprehensive analysis of genes regulating retinoic acid metabolism in chicken embryos reveals dynamic expression in the gonads. In particular, the retinoic acid-synthesising enzyme, RALDH2, is expressed in the left ovarian cortex at the time of STRA8 up-regulation, prior to meiosis.

Conclusion
This study presents the first molecular analysis of meiosis onset in an avian embryo. Although aspects of avian meiosis differ from that of mammals, a role for retinoic acid may be conserved.
Tracking the evolution of a cold stress associated gene family in cold tolerant grasses
Authors: Sandve Simen R , Rudi Heidi , Asp Torben , Rognli Odd Arne 
Published: September 2008

AbstractBackgroundGrasses are adapted to a wide range of climatic conditions. Species of the subfamily Pooideae, which includes wheat, barley and important forage grasses, have evolved extreme frost tolerance. A class of ice binding proteins that inhibit ice re-crystallisation, specific to the Pooideae subfamily lineage, have been identified in perennial ryegrass and wheat, and these proteins are thought to have evolved from a leucine-rich repeat phytosulfokine receptor kinase (LRR-PSR)-like ancestor gene. Even though the ice re-crystallisation inhibition function of these proteins has been studied extensivelyin vitro, little is known about the evolution of these genes on the molecular level.ResultsWe identified 15 putative novel ice re-crystallisation inhibition (IRI)-like protein coding genes in perennial ryegrass, barley, and wheat. Using synonymous divergence estimates we reconstructed the evolution of the IRI-like gene family. We also explored the hypothesis that the IRI-domain has evolved through repeated motif expansion and investigated the evolutionary relationship between a LRR-domain containing IRI coding gene in carrot and the Pooideae IRI-like genes. Our analysis showed that the main expansion of the IRI-gene family happened ~36 million years ago (Mya). In addition to IRI-like paralogs, wheat contained several sequences that likely were products of polyploidisation events (homoeologs). Through sequence analysis we identified two short motifs in the riceLRR-PSRgene highly similar to the repeat motifs of the IRI-domain in cold tolerant grasses. Finally we show that the LRR-domain of carrot and grass IRI proteins both share homology to anArabidopsis thalianaLRR-trans membrane protein kinase (LRR-TPK).ConclusionThe diverse IRI-like genes identified in this study tell a tale of a complex evolutionary history including birth of an ice binding domain, a burst of gene duplication events after cold tolerant grasses radiated from rice, protein domain structure differentiation between paralogs, and sub- and/or neofunctionalisation of IRI-like proteins. From our sequence analysis we provide evidence for IRI-domain evolution probably occurring through increased copy number of a repeated motif. Finally, we discuss the possibility of parallel evolution of LRR domain containing IRI proteins in carrot and grasses through two completely different molecular adaptations.