bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting Cancer Cells by Novel Engineered Modular Transporters
Authors: Gilyazova Dinara G. , Rosenkranz Andrey A. , Gulak Pavel V. , Lunin Vladimir G. , Sergienko Olga V. , Khramtsov Yuri V. , Timofeyev Kirill N. , Grin Mikhail A. , Mironov Andrey F. , Rubin Andrey B. , Georgiev Georgii P. , Sobolev Alexander S. 
Published: November 2006

Abstract
A major problem in the treatment of cancer is the specific targeting of drugs to these abnormal cells. Ideally, such a drug should act over short distances to minimize damage to healthy cells and target subcellular compartments that have the highest sensitivity to the drug. We describe the novel approach of using modular recombinant transporters to target photosensitizers to the nucleus, where their action is most pronounced, of cancer cells overexpressing ErbB1 receptors. We have produced a new generation of the transporters consisting of (a) epidermal growth factor as the internalizable ligand module to ErbB1 receptors, (b) the optimized nuclear localization sequence of SV40 large T-antigen, (c) a translocation domain of diphtheria toxin as an endosomolytic module, and (d) the Escherichia coli hemoglobin-like protein HMP as a carrier module. The modules retained their functions within the transporter chimera: they showed high-affinity interactions with ErbB1 receptors and α/β-importin dimers and formed holes in lipid bilayers at endosomal pH. A photosensitizer conjugated with the transporter produced singlet oxygen and ·OH radicals similar to the free photosensitizer. Photosensitizers-transporter conjugates have &gt;3,000 times greater efficacy than free photosensitizers for target cells and were not photocytotoxic at these concentrations for cells expressing a few ErbB1 receptors per cell, in contrast to free photosensitizers. The different modules of the transporters, which are highly expressed and easily purified to retain full activity of each of the modules, are interchangeable, meaning that they can be tailored for particular applications. (Cancer Res 2006; 66(21): 10534-40)
Inappropriate Activation of the Androgen Receptor by Nonsteroids: Involvement of the Src Kinase Pathway and Its Therapeutic Implications
Authors: Desai Sonal J. , Ma Ai-Hong , Tepper Clifford G. , Chen Hong-Wu , Kung Hsing-Jien 
Published: November 2006

Abstract
The inappropriate activation of androgen receptor (AR) by nonsteroids is considered a potential mechanism in the emergence of hormone-refractory prostate tumors, but little is known about the properties of these “pseudoactivated” AR. Here, we present the first comprehensive analysis closely examining the properties of AR activated by the neuropeptide bombesin that distinguish it from androgen-activated AR. We show that bombesin-activated AR (a) is required for bombesin-induced growth of LNCaP cells, (b) has a transcriptional profile overlapping with, but not identical to, androgen-activated AR, (c) activates prostate-specific antigen by preferentially binding to its proximal promoter, and (d) assembles a distinct coactivator complex. Significantly, we found that Src kinase is critical for bombesin-induced AR-mediated activity and is required for translocation and transactivation of AR. Additionally, we identify c-Myc, a Src target gene, to be activated by bombesin and a potential coactivator of AR-mediated activity specific to bombesin-induced signaling. Because Src kinase is often activated by other nonsteroids, such as other neuropeptides, growth factors, chemokines, and cytokines, our findings have general applicability and provide rationale for investigating the efficacy of the Src kinase pathway as a target for the prevention of relapsed prostate cancers. (Cancer Res 2006; 66(21): 10449-59)
Immune regulation by pretenders: cell-to-cell transfers of HLA-G make effector T cells act as regulatory cells
Authors: LeMaoult Joel , Caumartin Julien , Daouya Marina , Favier Benoit , Rond Solene Le , Gonzalez Alvaro , Carosella Edgardo D. 
Published: November 2006

AbstractTrogocytosis is the uptake of membrane fragments from one cell by another and has been described for immune cells in mice and humans. Functional consequences of trogocytosis are emerging, but a dramatic immune function has still to be associated with it. Here we show that some resting, and most activated, CD4+ and CD8+ T cells acquire immunosuppressive HLA-G1 from antigen-presenting cells (APCs) in a few minutes. Acquisition of HLA-G through membrane transfers does not change the real nature of the T cells but immediately reverses their function from effectors to regulatory cells. These regulatory cells can inhibit allo-proliferative responses through HLA-G1 that they acquired. These data demonstrate that trogocytosis of HLA-G1 leads to instant generation of a new type of regulatory cells, which act through cell-surface molecules they temporarily display but do not express themselves. Such regulatory cells whose existence is most likely limited in space and time might constitute an “emergency” immune suppression mechanism used by HLA-G–expressing tissues to protect themselves against immune aggression. In addition, T cells acquire from HLA-G–expressing APCs their HLA-G–dependent capability to induce the slower differentiation of regulatory cells that act independently of HLA-G. These data re-emphasize the significance of HLA-G expression in normal and pathologic situations.
FGF2 posttranscriptionally down-regulates expression of SDF1 in bone marrow stromal cells through FGFR1 IIIc
Authors: Nakayama Takayuki , Mutsuga Noriko , Tosato Giovanna 
Published: November 2006

AbstractThe chemokine stromal cell–derived factor-1 (SDF-1) is constitutively expressed by bone marrow stromal cells and plays key roles in hematopoiesis. Fibroblast growth factor 2 (FGF2), a member of the FGF family that plays important roles in developmental morphogenic processes, is abnormally elevated in the bone marrow from patients with clonal myeloid disorders and other disorders where normal hematopoiesis is impaired. Here, we report that FGF2 reduces SDF-1 secretion and protein content in bone marrow stromal cells. By inhibiting SDF-1 production, FGF2 compromises stromal cell support of hematopoietic progenitor cells. Reverse-transcriptase–polymerase chain reaction (RT-PCR) analysis revealed that bone marrow stromal cells express 5 FGF receptors (FGFRs) among the 7 known FGFR subtypes. Blocking experiments identified FGFR1 IIIc as the receptor mediating FGF2 inhibition of SDF-1 expression in bone marrow stromal cells. Analysis of the mechanisms underlying FGF2 inhibition of SDF-1 production in bone marrow stromal cells revealed that FGF2 reduces the SDF-1 mRNA content by posttranscriptionally accelerating SDF-1 mRNA decay. Thus, we identify FGF2 as an inhibitor of SDF-1 production in bone marrow stromal cells and a regulator of stromal cell supportive functions for hematopoietic progenitor cells.
Bone morphogenic protein antagonist Drm/gremlin is a novel proangiogenic factor
Authors: Stabile Helena , Mitola Stefania , Moroni Emanuela , Belleri Mirella , Nicoli Stefania , Coltrini Daniela , Peri Francesco , Pessi Antonello , Orsatti Laura , Talamo Fabio , Castronovo Vincent , Waltregny David , Cotelli Franco , Ribatti Domenico , Presta Marco 
Published: November 2006

AbstractAngiogenesis plays a key role in various physiologic and pathologic conditions, including tumor growth. Drm/gremlin, a member the Dan family of bone morphogenic protein (BMP) antagonists, is commonly thought to affect different processes during growth, differentiation, and development by heterodimerizing various BMPs. Here, we identify Drm/gremlin as a novel proangiogenic factor expressed by endothelium. Indeed, Drm/gremlin was purified to homogeneity from the conditioned medium of transformed endothelial cells using an endothelial-cell sprouting assay to follow protein isolation. Accordingly, recombinant Drm/gremlin stimulates endothelial-cell migration and invasion in fibrin and collagen gels, binds with high affinity to various endothelial cell types, and triggers tyrosine phosphorylation of intracellular signaling proteins. Also, Drm/gremlin induces neovascularization in the chick embryo chorioallantoic membrane. BMP4 does not affect Drm/gremlin interaction with endothelium, and both molecules exert a proangiogenic activity in vitro and in vivo when administered alone or in combination. Finally, Drm/gremlin is produced by the stroma of human tumor xenografts in nude mice, and it is highly expressed in endothelial cells of human lung tumor vasculature when compared with non-neoplastic lung. Our observations point to a novel, previously unrecognized capacity of Drm/gremlin to interact directly with target endothelial cells and to modulate angiogenesis.
Defective ALK5 signaling in the neural crest leads to increased postmigratory neural crest cell apoptosis and severe outflow tract defects
Authors: Wang Jikui , Nagy Andre , Larsson Jonas , Dudas Marek , Sucov Henry M , Kaartinen Vesa 
Published: November 2006

Abstract

Background
Congenital cardiovascular diseases are the most common form of birth defects in humans. A substantial portion of these defects has been associated with inappropriate induction, migration, differentiation and patterning of pluripotent cardiac neural crest stem cells. While TGF-β-superfamily signaling has been strongly implicated in neural crest cell development, the detailed molecular signaling mechanisms in vivo are still poorly understood.

Results
We deleted the TGF-β type I receptor Alk5 specifically in the mouse neural crest cell lineage. Failure in signaling via ALK5 leads to severe cardiovascular and pharyngeal defects, including inappropriate remodeling of pharyngeal arch arteries, abnormal aortic sac development, failure in pharyngeal organ migration and persistent truncus arteriosus. While ALK5 is not required for neural crest cell migration, our results demonstrate that it plays an important role in the survival of post-migratory cardiac neural crest cells.

Conclusion
Our results demonstrate that ALK5-mediated signaling in neural crest cells plays an essential cell-autonomous role in the pharyngeal and cardiac outflow tract development.
Obstructive sleep apnoea is independently associated with the metabolic syndrome but not insulin resistance state
Authors: Gruber A , Horwood F , Sithole J , Ali NJ , Idris I 
Published: November 2006

Abstract
Obstructive sleep apnoea (OSA) is a cardio-metabolic disorder. Whether metabolic syndrome (MS), insulin resistance (IR) and albuminuria are independently associated with OSA is unclear, but defining the interactions between OSA and various cardiovascular (CV) risk factors independent of obesity facilitates the development of therapeutic strategies to mitigate their increased CV risks. We prospectively recruited 38 subjects with OSA and 41 controls. Anthropometric measurements, glucose, lipids, insulin and blood pressure (BP) were measured after an overnight fast. IR state was defined as homeostasis model assessment (HOMA) value >3.99 and MS diagnosed according to the International Diabetes Federation (IDF) criteria. Subjects with OSA were more obese, more insulin resistant, more hyperglycaemic, had higher Epworth score (measure of day time somnolence) and systolic blood pressure levels. The prevalence of MS was higher in OSA compared with non-OSA subjects (74% vs 24%, p < 0.001). The prevalence of microalbuminuria in both groups was negligible. Logistic regression adjusted for age, BMI and smoking showed that the patient with OSA was 5.9 (95% CI 2.0–17.6) times more likely to have MS than non-OSA patient. Triglyceride (p = 0.031), glucose (0.023) and Epworth score (0.003) values were independently associated with OSA after adjusting for BMI and other covariates whilst IR status was found not to be significant. Using the ROC curve analysis, we found that a waist circumference of >103 cm would predict MS in patients with OSA at 75–78% sensitivity and 61–64% specificity. The agreement between MS and IR state in this cohort is poor. Thus, OSA is associated with MS independent of obesity predominantly due to increased triglyceride, glucose and Epworth score values but not IR or microalbuminuria status. This observation suggests an alternative pathogenic factor mediating the increased cardiovascular risk in patients with OSA and MS, other than that due to IR. The independent link between Epworth score and MS in patients with OSA implicates the role of daytime sleepiness and chronic hypoxia as a potential mediator. Given the discordant between MS and IR state, measurement of waist is useful for predicting mainly MS but not insulin resistance status in patients with OSA. Appropriate pharmacological intervention targeting these independent factors is important in reducing the increased CV risks among patients with OSA.
Interactions between IL-32 and tumor necrosis factor alpha contribute to the exacerbation of immune-inflammatory diseases
Authors: Shoda Hirofumi , Fujio Keishi , Yamaguchi Yumi , Okamoto Akiko , Sawada Tetsuji , Kochi Yuta , Yamamoto Kazuhiko 
Published: November 2006

AbstractIL-32 is a newly described cytokine in the human found to be an in vitro inducer of tumor necrosis factor alpha (TNFα). We examined the in vivo relationship between IL-32 and TNFα, and the pathologic role of IL-32 in the TNFα-related diseases – arthritis and colitis. We demonstrated by quantitative PCR assay that IL-32 mRNA was expressed in the lymphoid tissues, and in stimulated peripheral T cells, monocytes, and B cells. Activated T cells were important for IL-32 mRNA expression in monocytes and B cells. Interestingly, TNFα reciprocally induced IL-32 mRNA expression in T cells, monocyte-derived dendritic cells, and synovial fibroblasts. Moreover, IL-32 mRNA expression was prominent in the synovial tissues of rheumatoid arthritis patients, especially in synovial-infiltrated lymphocytes by in situ hybridization. To examine the in vivo relationship of IL-32 and TNFα, we prepared an overexpression model mouse of human IL-32β (BM-hIL-32) by bone marrow transplantation. Splenocytes of BM-hIL-32 mice showed increased expression and secretion of TNFα, IL-1β, and IL-6 especially in response to lipopolysaccharide stimulation. Moreover, serum TNFα concentration showed a clear increase in BM-hIL-32 mice. Cell-sorting analysis of splenocytes showed that the expression of TNFα was increased in resting F4/80+ macrophages, and the expression of TNFα, IL-1β and IL-6 was increased in lipopolysaccharide-stimulated F4/80+ macrophages and CD11c+ dendritic cells. In fact, BM-hIL-32 mice showed exacerbation of collagen-antibody-induced arthritis and trinitrobenzen sulfonic acid-induced colitis. In addition, the transfer of hIL-32β-producing CD4+ T cells significantly exacerbated collagen-induced arthritis, and a TNFα blockade cancelled the exacerbating effects of hIL-32β. We therefore conclude that IL-32 is closely associated with TNFα, and contributes to the exacerbation of TNFα-related inflammatory arthritis and colitis.
Eggs regulate sperm flagellar motility initiation, chemotaxis and inhibition in the coralAcropora digitifera,A. gemmiferaandA. tenuis
Authors: Morita Masaya , Nishikawa Akira , Nakajima Ayako , Iguchi Akira , Sakai Kazuhiko , Takemura Akihiro , Okuno Makoto 
Published: November 2006

SUMMARYCorals perform simultaneous mass spawning around the full moon. Most Acropora species release gamete bundles, which are a complex of eggs and sperm, into the seawater. Then, gamete bundles are separated into eggs and sperm. Eggs are fertilized when sperm and eggs come in contact with each other. However, it is still unclear how sperm meet the eggs of the same species in the presence of many eggs of different species and how eggs guard against the fertilization attempts by sperm of different species. In this study, we observed that A. digitifera, A. gemmifera and A. tenuis sperm showed motility initiation/attraction close to eggs. Sperm were completely immotile in seawater, but they began to swim in circular motion when they came in close proximity to eggs, and then approached the eggs in straightforward paths. Sperm flagellar motility was not activated by an egg from different species, suggesting that motility initiation by the egg is species specific. In addition, hybridization among these species did not occur under observed conditions. Furthermore, motility-activated sperm became quiescent when many sperm approached the eggs. This study is the first report to show that the egg secretes immobilization factor(s). Our results suggest that the flagellar motility regulation has evolved to avoid hybridization among different species during the mass spawning.
Dolphin foraging sounds suppress calling and elevate stress hormone levels in a prey species, the Gulf toadfish
Authors: Remage-Healey Luke , Nowacek Douglas P. , Bass Andrew H. 
Published: November 2006

SUMMARY
The passive listening hypothesis proposes that dolphins and whales detect acoustic signals emitted by prey, including sound-producing (soniferous)fishes. Previous work showed that bottlenose dolphins (Tursiops truncatus) behaviorally orient toward the sounds of prey, including the advertisement calls of male Gulf toadfish (Opsanus beta). In addition, soniferous fishes constitute over 80% of Tursiops diet, and toadfishes alone account for approximately 13% of the stomach contents of adult bottlenose dolphins. Here, we used both behavioral (vocalizations) and physiological (plasma cortisol levels) parameters to determine if male Gulf toadfish can, in turn, detect the acoustic signals of bottlenose dolphins. Using underwater playbacks to toadfish in their natural environment, we found that low-frequency dolphin sounds (`pops') within the toadfish's range of hearing dramatically reduce toadfish calling rates by 50%. Highfrequency dolphin sounds (whistles) and low-frequency snapping shrimp pops (ambient control sounds) each had no effect on toadfish calling rates. Predator sound playbacks also had consequences for circulating stress hormones, as cortisol levels were significantly elevated in male toadfish exposed to dolphin pops compared with snapping shrimp pops. These findings lend strong support to the hypothesis that individuals of a prey species modulate communication behavior in the presence of a predator, and also suggest that short-term glucocorticoid elevation is associated with anti-predator behavior.
Seasonal adjustment of energy budget in a large wild mammal, the Przewalski horse (Equus ferus przewalskii) II. Energy expenditure
Authors: Arnold Walter , Ruf Thomas , Kuntz Regina 
Published: November 2006

SUMMARY
Many large mammals show pronounced seasonal fluctuations of metabolic rate(MR). It has been argued, based on studies in ruminants, that this variation merely results from different levels of locomotor activity (LA), and heat increment of feeding (HI). However, a recent study in red deer (Cervus elaphus) identified a previously unknown mechanism in ungulates -nocturnal hypometabolism - that contributed significantly to reduced energy expenditure, mainly during late winter. The relative contribution of these different mechanisms to seasonal adjustments of MR is still unknown, however. Therefore, in the study presented here we quantified for the first time the independent contribution of thermoregulation, LA and HI to heart rate(fH) as a measure of MR in a free-roaming large ungulate,the Przewalski horse or Takhi (Equus ferus przewalskii Poljakow).
f H varied periodically throughout the year with a twofold increase from a mean of 44 beats min-1 during December and January to a spring peak of 89 beats min-1 at the beginning of May. LA increased from 23% per day during December and January to a mean level of 53% per day during May, and declined again thereafter. Daily mean subcutaneous body temperature (Ts) declined continuously during winter and reached a nadir at the beginning of April (annual range was 5.8°C),well after the annual low of air temperature and LA.
Lower Ts during winter contributed considerably to the reduction in fH. In addition to thermoregulation, fH was affected by reproduction, LA, HI and unexplained seasonal variation, presumably reflecting to some degree changes in organ mass. The observed phase relations of seasonal changes indicate that energy expenditure was not a consequence of energy uptake but is under endogenous control, preparing the organism well in advance of seasonal energetic demands.
Severe laryngeal stenosis repair: Long‐term follow‐up using conjoint hyoid bone segments
Authors: Abedi Esrafil , Frable Mary Ann Smith 
Published: November 2006

AbstractIn early 1983 the authors presented an innovative procedure for the management of severe laryngeal stenosis. Because of the severity of the stenosis and the large surgical defect created by excision of the stenosis, multiple pieces of the hyoid bone were sewn together conjointly to bridge the surgical defect. The authors are now able to report follow‐up in 6 patients ranging from 11 to 60 months and discuss their favorable experience with this procedure.
Combined intracranial and extracranial excision of nasopharyngeal angiofibroma
Authors: Standefer John , Holt G. Richard , Brown Willis E. , Gates George A. 
Published: November 2006

AbstractOf all angiofibromas, 10% to 20% may have intracranial extensions or receive vascular supply from the internal carotid artery. Until recently, the treatment of intracranial involvement has been radiation therapy. However, with improved anesthetic and neurosurgical techniques, transfusion capabilities and embolotherapy, the combined intracranial and extracranial excision of an angiofibroma has resulted in a low morbidity and mortality and a greater chance for complete excision of the tumor. The authors present the management of three patients with intracranial involvement of their tumors. Use of the midfacial degloving approach to the nasal cavity and paranasal sinuses has resulted in a significant improvement in the cosmetic appearance postoperatively.
Primary cysts of the mastoid process
Authors: Zimmerman Bruce E. , Proud G. O. 
Published: November 2006

AbstractTwo patients with primary mastoid cysts are presented. These examples stress the importance of regular follow‐up of patients with chronic serous otitis media so that the complications or associated abnormalities may be treated early prior to extensive destructive erosion. The formation of these cysts may be due to changes brought about by chronic serous otitis media, or they may be of congenital origin with middle ear effusion as a sequela.
Total glossectomy sans laryngectomy — Are we justified?
Authors: Pradhan Sultan A. , Rajpal Ram M. 
Published: November 2006

AbstractEighty‐five cases of cancer of the tongue treated with total glossectomy are presented; 82 had a squamous carcinoma. The majority had a large primary with no disease in the neck. Thus only 6 patients required concurrent therapeutic radical neck dissection. A laryngectomy was done in 9 cases for gross extension of disease and in 1, as prophylaxis against aspiration.In 75 cases the larynx was preserved. Mortality from aspiration pneumonitis was 4%. Local recurrence rate was 42% for predominantly posterior lesions and 27% for anterior lesions. The speech, though not quite articulate, was fairly understandable. Thus, in cases of total glossectomy preservation of larynx is worthwhile and justifiable except when involved with disease, when the risk of even minor degrees of aspiration is high (elderly, frail individuals) and with associated extensive pharyngeal resection hampering the swallowing machanism.