tbuckley/cabot-search huggingface dataset:
Obligate mutualism within a host drives the extreme specialization of a fig wasp genome
Authors: Jin-Hua Xiao, Zhen Yue, Ling-Yi Jia, Xin-Hua Yang, Li-Hua Niu, Zhuo Wang, Peng Zhang, Bao-Fa Sun, Shun-Min He, Zi Li, Tuan-Lin Xiong, Wen Xin, Hai-Feng Gu, Bo Wang, John H Werren, Robert W Murphy, David Wheeler, Li-Ming Niu, Guang-Chang Ma, Ting Tang, Sheng-Nan Bian, Ning-Xin Wang, Chun-Yan Yang, Nan Wang, Yue-Guan Fu, Wen-Zhu Li, Soojin V Yi, Xing-Yu Yang, Qing Zhou, Chang-Xin Lu, Chun-Yan Xu, Li-Juan He, Li-Li Yu, Ming Chen, Yuan Zheng, Shao-Wei Wang, Shuang Zhao, Yan-Hong Li, Yang-Yang Yu, Xiao-Ju Qian, Yue Cai, Lian-Le Bian, Shu Zhang, Jun-Yi Wang, Ye Yin, Hui Xiao, Guan-Hong Wang, Hui Yu, Wen-Shan Wu, James M Cook, Jun Wang, Da-Wei Huang
Journal: Genome biology (2013)

Fig pollinating wasps form obligate symbioses with their fig hosts. This mutualism arose approximately 75 million years ago. Unlike many other intimate symbioses, which involve vertical transmission of symbionts to host offspring, female fig wasps fly great distances to transfer horizontally between hosts. In contrast, male wasps are wingless and cannot disperse. Symbionts that keep intimate contact with their hosts often show genome reduction, but it is not clear if the wide dispersal of female fig wasps will counteract this general tendency. We sequenced the genome of the fig wasp Ceratosolen solmsi to address this question.The genome size of the fig wasp C. solmsi is typical of insects, but has undergone dramatic reductions of gene families involved in environmental sensing and detoxification. The streamlined chemosensory ability reflects the overwhelming importance of females finding trees of their only host species, Ficus hispida, during their fleeting adult lives. Despite long-distance dispersal, little need exists for detoxification or environmental protection because fig wasps spend nearly all of their lives inside a largely benign host. Analyses of transcriptomes in females and males at four key life stages reveal that the extreme anatomical sexual dimorphism of fig wasps may result from a strong bias in sex-differential gene expression.Our comparison of the C. solmsi genome with other insects provides new insights into the evolution of obligate mutualism. The draft genome of the fig wasp, and transcriptomic comparisons between both sexes at four different life stages, provide insights into the molecular basis for the extreme anatomical sexual dimorphism of this species.
Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome
Authors: Andrew J Sharp, Sierra Hansen, Rebecca R Selzer, Ze Cheng, Regina Regan, Jane A Hurst, Helen Stewart, Sue M Price, Edward Blair, Raoul C Hennekam, Carrie A Fitzpatrick, Rick Segraves, Todd A Richmond, Cheryl Guiver, Donna G Albertson, Daniel Pinkel, Peggy S Eis, Stuart Schwartz, Samantha J L Knight, Evan E Eichler
Journal: Nature Genetics (2006)
Effect of inhaled prostaglandin E2 on bronchial reactivity to sodium metabisulphite and methacholine in patients with asthma.
Authors: I D Pavord, A Wisniewski, R Mathur, I Wahedna, A J Knox, A E Tattersfield
Journal: Thorax (1991)

Inhaled frusemide protects against the bronchoconstrictor response to a wide range of stimuli that cause bronchoconstriction by indirect mechanisms. One possible explanation for this protection relates to the known ability of frusemide to enhance synthesis of prostaglandin E2 (PGE2). Studies in vitro suggest that PGE2 might protect against indirectly acting bronchoconstrictor challenges rather than those that act directly on airway smooth muscle, though little is known about the effects of PGE2 in vivo. The effect of inhaled PGE2 on the bronchoconstrictor response to inhaled sodium metabisulphite (a stimulus with an indirect action) and methacholine (which acts directly on airway smooth muscle) was studied in nine patients with asthma. Subjects were studied on four days, inhaling PGE2 (100 micrograms) or placebo in a double blind fashion followed immediately by a cumulative dose challenge with sodium metabisulphite or methacholine. The response to the constrictor stimuli was measured as the provocative dose causing a 20% fall in FEV1 (PD20). There was no significant change in FEV1 after inhaled PGE2 compared with placebo, nor any significant change in the response to methacholine; the geometric mean methacholine PD20 was 0.9 mumol after PGE2 and 0.56 mumol after placebo (mean difference 0.7 (95% confidence limits--0.1, 1.5) doubling doses). PGE2, however, protected against sodium metabisulphite, the geometric mean sodium metabisulphite PD20 being 11.8 mumol after PGE2 and 1.8 mumol after placebo (mean difference 2.5 (95% CL 1.9, 3.1) doubling doses). PGE2 conferred significantly greater protection against sodium metabisulphite than methacholine (mean difference 1.8 (95% CL 0.8, 2.8) doubling doses). This suggests that PGE2, like frusemide, has an inhibitory effect on pathways relevant to the bronchoconstriction induced by sodium metabisulphite, with little or no effect on those relevant to methacholine.
B Lymphocyte Memory
Authors: Robert A. Barrington, Olga Pozdnyakova, Mohammad R. Zafari, Christopher D. Benjamin, Michael C. Carroll
Journal: The Journal of Experimental Medicine (2002)

To dissect the influence of CD21/CD35 and FcγRIIB in antigen retention and humoral memory, we used an adoptive transfer model in which antigen-primed B and T lymphocytes were given to sublethally irradiated wild-type mice or mice deficient in CD21/CD35 (Cr2−/−) or FcγRIIB receptors (FcγRIIB−/−). Cr2−/− chimeras showed impaired memory as characterized by a decrease in antibody titer, reduced frequency of antibody secreting cells, an absence of affinity maturation, and significantly reduced recall response. The impaired memory in Cr2−/− chimeras corresponded with the reduced frequency of antigen-specific memory B cells. Interestingly, FcγRIIB−/− chimeras showed a differential phenotype with impaired splenic but normal bone marrow responses. These data suggest that CD21/CD35 on stroma, including follicular dendritic cells, is critical to the maintenance of long-term B lymphocyte memory.
The neurocognitive effects of radiation in adult low-grade glioma patients
Authors: Paul D. Brown, Jan C. Buckner, Joon H. Uhm, Edward G. Shaw
Journal: Neuro-Oncology (2003)

Radiotherapy is a component of the treatment regimen for the majority of patients with low-grade gliomas. Therefore, the effect of radiotherapy on the long-term cognitive performance of these patients is a major concern. This article reviews the neurocognitive effects of radiotherapy on patients with low-grade gliomas. The weight of evidence suggests only sporadic, limited neurocognitive damage from focal radiotherapy at the doses usually prescribed for low-grade gliomas.
Successful correction of the human β-thalassemia major phenotype using a lentiviral vector
Authors: Geetha Puthenveetil, Jessica Scholes, Denysha Carbonell, Naveen Qureshi, Ping Xia, Licheng Zeng, Shulian Li, Ying Yu, Alan L Hiti, Jiing-Kuan Yee, Punam Malik
Journal: Blood (2004)
Stem cell factor SALL4, a potential prognostic marker for myelodysplastic syndromes
Authors: Fei Wang, Ye Guo, Qian Chen, Zhuo Yang, Ning Ning, Yujuan Zhang, Yonggang Xu, Xiaodong Xu, Chunrong Tong, Li Chai, Wei Cui
Journal: Journal of Hematology & Oncology (2013)

Abstract Background Myelodysplastic syndromes (MDS) are a group of heterogeneous diseases with variable clinical course. Predicting disease progression is difficult due to lack of specific molecular marker(s). SALL4 plays important roles in normal hematopoiesis and leukemogenesis. SALL4 transgenic mice develop MDS prior to acute myeloid leukemia (AML) transformation. However, the role of SALL4 in human MDS has not been extensively investigated. In this study, we evaluate the diagnostic/prognostic value of SALL4 in MDS by examining its expression levels in a cohort of MDS patients. Methods Fifty-five newly diagnosed MDS, twenty MDS-AML, and sixteen post-treatment MDS patients were selected for our study along with ten healthy donors. Results We demonstrated that SALL4 was over-expressed in MDS patients and proportionally increased in MDS patients with high grade/IPSS scores. This expression pattern was similar to that of Bmi-1, an important marker in predicting MDS/AML progression. In addition, the level of SALL4 was positively correlated with increased blast counts, high-risk keryotypes and increased significantly in MDS-AML transformation. Furthermore, higher level of SALL4 expression was associated with worse survival rates and SALL4 level decreased following effective therapy. Conclusions To the best of our knowledge, this is the largest series and the first to report the expression pattern of SALL4 in detail in various subtypes of MDS in comparison to that of Bmi-1. We conclude that SALL4 is a potential molecular marker in predicting the prognosis of MDS.
Evaluation of Serum 1,5 Anhydroglucitol Levels as a Clinical Test to Differentiate Subtypes of Diabetes
Authors: Aparna Pal, Andrew J. Farmer, Christina Dudley, Mary P. Selwood, Beryl A. Barrow, Rhiannon Klyne, Jilly P. Grew, Mark I. McCarthy, Anna L. Gloyn, Katharine R. Owen
Journal: Diabetes Care (2009)

OBJECTIVE Assignment of the correct molecular diagnosis in diabetes is necessary for informed decisions regarding treatment and prognosis. Better clinical markers would facilitate discrimination and prioritization for genetic testing between diabetes subtypes. Serum 1,5 anhydroglucitol (1,5AG) levels were reported to differentiate maturity-onset diabetes of the young due to HNF1A mutations (HNF1A-MODY) from type 2 diabetes, but this requires further validation. We evaluated serum 1,5AG in a range of diabetes subtypes as an adjunct for defining diabetes etiology. RESEARCH DESIGN AND METHODS 1,5AG was measured in U.K. subjects with: HNF1A-MODY (n = 23), MODY due to glucokinase mutations (GCK-MODY, n = 23), type 1 diabetes (n = 29), latent autoimmune diabetes in adults (LADA, n = 42), and type 2 diabetes (n = 206). Receiver operating characteristic curve analysis was performed to assess discriminative accuracy of 1,5AG for diabetes etiology. RESULTS Mean (SD range) 1,5AG levels were: GCK-MODY 13.06 μg/ml (5.74–29.74), HNF1A-MODY 4.23 μg/ml (2.12–8.44), type 1 diabetes 3.09 μg/ml (1.45–6.57), LADA 3.46 μg/ml (1.42–8.45), and type 2 diabetes 5.43 (2.12–13.23). Levels in GCK-MODY were higher than in other groups (P &amp;lt; 10−4 vs. each group). HNF1A-MODY subjects showed no difference in unadjusted 1,5AG levels from type 2 diabetes, type 1 diabetes, and LADA. Adjusting for A1C revealed a difference between HNF1A-MODY and type 2 diabetes (P = 0.001). The discriminative accuracy of unadjusted 1,5AG levels was 0.79 for GCK-MODY versus type 2 diabetes and 0.86 for GCK-MODY versus HNF1A-MODY but was only 0.60 for HNF1A-MODY versus type 2 diabetes. CONCLUSIONS In our dataset, serum 1,5AG performed well in discriminating GCK-MODY from other diabetes subtypes, particularly HNF1A-MODY. Measurement of 1,5AG levels could inform decisions regarding MODY diagnostic testing.
CCR2 promotes hepatic fibrosis in mice
Authors: Ekihiro Seki, Samuele de Minicis, Sayaka Inokuchi, Kojiro Taura, Katsumi Miyai, Nico van Rooijen, Robert F. Schwabe, David A. Brenner
Journal: Hepatology (2009)

Chemokines and chemokine receptors contribute to the migration of hepatic stellate cells (HSCs) and Kupffer cells, two key cell types in fibrogenesis. Here, we investigate the role of CCR2, the receptor for monocyte chemoattractant protein (MCP)-1, MCP-2, and MCP-3, in hepatic fibrosis. Hepatic CCR2, MCP-1, MCP-2, and MCP-3 messenger RNA expression was increased after bile duct ligation (BDL). Both Kupffer cells and HSCs, but not hepatocytes, expressed CCR2. BDL- and CCl(4)-induced fibrosis was markedly reduced in CCR2(-/-) mice as assessed through collagen deposition, alpha-smooth muscle actin expression, and hepatic hydroxyproline content. We generated CCR2 chimeric mice by the combination of clodronate, irradiation, and bone marrow (BM) transplantation allowing full reconstitution of Kupffer cells, but not HSCs, with BM cells. Chimeric mice containing wild-type BM displayed increased macrophage recruitment, whereas chimeric mice containing CCR2(-/-) BM showed less macrophage recruitment at 5 days after BDL. Although CCR2 expressed in the BM enhanced macrophage recruitment in early phases of injury, CCR2 expression on resident liver cells including HSCs, but not on the BM, was required for fibrogenic responses in chronic fibrosis models. In vitro experiments demonstrated that HSCs deficient in CCR2(-/-) or its downstream mediator p47phox(-/-) did not display extracellular signal-regulated kinase and AKT phosphorylation, chemotaxis, or reactive oxygen species production in response to MCP-1, MCP-2, and MCP-3.Our results indicate that CCR2 promotes HSC chemotaxis and the development of hepatic fibrosis.
Integrated Positron Emission Tomography/Computed Tomography May Render Bone Scintigraphy Unnecessary to Investigate Suspected Metastatic Breast Cancer
Authors: Patrick G. Morris, Colleen Lynch, John N. Feeney, Sujata Patil, Jane Howard, Steven M. Larson, Maura Dickler, Clifford A. Hudis, Maxine Jochelson, Heather L. McArthur
Journal: Journal of Clinical Oncology (2010)

Purpose Although the accurate detection of osseous metastases in the evaluation of patients with suspected metastatic breast cancer (MBC) has significant prognostic and therapeutic implications, the ideal diagnostic approach is uncertain. In this retrospective, single-institution study, we compare the diagnostic performance of integrated positron emission tomography/computed tomography (PET/CT) and bone scintigraphy (BSc) in women with suspected MBC. Patients and Methods Women with suspected MBC evaluated with PET/CT and BSc (within 30 days) between January 1, 2003 and June 30, 2008, were identified through institutional databases. Electronic medical records were reviewed, and radiology reports were classified as positive/negative/equivocal for osseous metastases. A nuclear medicine radiologist (blinded to correlative and clinical end points) reviewed all equivocal PET/CT and BSc images and reclassified some reports. Final PET/CT and BSc classifications were compared. Baseline patient/tumor characteristics and bone pathology were recorded and compared to the final imaging results. Results We identified 163 women who had a median age of 52 years (range, 30 to 90 years); 32% had locally advanced breast cancer, 42% had been diagnosed with breast cancer less than 12 weeks before identification. Twenty studies were originally deemed equivocal (five with PET/CT, and 15 with BSc), and 13 (65%) of these studies were reclassified after radiology review. Overall, PET/CT and BSc were highly concordant for reporting osseous metastases with 132 paired studies (81%); 32 (20%) were positive, and 100 (61%) were negative. Thirty-one occurrences (19%) were discordant. Twelve of these (39%) had pathology confirming osseous metastases: nine (of 18) were PET/CT positive and BSc negative; one (of three) was PET/CT positive and BSc equivocal; and two (of two) were PET/CT equivocal and BSc negative. Conclusion This study supports the use of PET/CT in detecting osseous metastases for suspected MBC. Whether PET/CT may supplant BSc in this setting is unknown.
A novel role for ursodeoxycholic acid in inhibiting apoptosis by modulating mitochondrial membrane perturbation.
Authors: C M Rodrigues, G Fan, X Ma, B T Kren, C J Steer
Journal: Journal of Clinical Investigation (1998)

The hydrophilic bile salt ursodeoxycholic acid (UDCA) protects against the membrane-damaging effects associated with hydrophobic bile acids. This study was undertaken to (a) determine if UDCA inhibits apoptosis from deoxycholic acid (DCA), as well as from ethanol, TGF-beta1, Fas ligand, and okadaic acid; and to (b) determine whether mitochondrial membrane perturbation is modulated by UDCA. DCA induced significant hepatocyte apoptosis in vivo and in isolated hepatocytes determined by terminal transferase-mediated dUTP-digoxigenin nick end-labeling assay and nuclear staining, respectively (P < 0.001). Apoptosis in isolated rat hepatocytes increased 12-fold after incubation with 0.5% ethanol (P < 0.001). HuH-7 cells exhibited increased apoptosis with 1 nM TGF-beta1 (P < 0. 001) or DCA at >/= 100 microM (P < 0.001), as did Hep G2 cells after incubation with anti-Fas antibody (P < 0.001). Finally, incubation with okadaic acid induced significant apoptosis in HuH-7, Saos-2, Cos-7, and HeLa cells. Coadministration of UDCA with each of the apoptosis-inducing agents was associated with a 50-100% inhibition of apoptotic changes (P < 0.001) in all the cell types. Also, UDCA reduced the mitochondrial membrane permeability transition (MPT) in isolated mitochondria associated with both DCA and phenylarsine oxide by > 40 and 50%, respectively (P < 0.001). FACS(R) analysis revealed that the apoptosis-inducing agents decreased the mitochondrial transmembrane potential and increased reactive oxygen species production (P < 0.05). Coadministration of UDCA was associated with significant prevention of mitochondrial membrane alterations in all cell types. The results suggest that UDCA plays a central role in modulating the apoptotic threshold in both hepatocytes and nonliver cells, and inhibition of MPT is at least one pathway by which UDCA protects against apoptosis.
Steroid treatment based on the findings of transbronchial biopsy in idiopathic interstitial pneumonia
Authors: K. Watanabe, K. Higuchi, K. Ninomiya, T. Ohshima, T. Aritomi, Y. Kawabata, M. Yoshida
Journal: European Respiratory Journal (2002)

This study was performed to find the rationale for administering steroids to patients with idiopathic interstitial pneumonia (IIP), which was unlikely to be usual interstitial pneumonia (UIP) but was not surgically biopsied. Among IIP patients in the file of the departments, nine patients who met the following criteria were selected for this study ("non-UIP" group): 1) transbronchial lung biopsy showed dense mononuclear cell infiltration in thickened alveolar septa; 2) chest radiograph and computed tomography showed irregular linear, reticular or ground-glass opacities with alveolar consolidation without honeycombing in the lung base; and 3) spirometry was performed before and after steroid therapy. Ten patients with pathologically confirmed nonspecific interstitial pneumonia ("NSIP" group) were also selected for the comparison. Baseline values and percentage increase of vital capacity (VC) after steroid therapy were plotted. Steroids improved VC in both groups of patients. After 1 yr of steroid therapy, percentage increase of VC in "non-UIP" was 28.8+/-7.7%, which was not significantly different from that in NSIP (30.0+/-11.7%). One "non-UIP" patient and one NSIP patient died after 6.4 and 4.3 yrs of follow-up, respectively. Patients with idiopathic interstitial pneumonia presenting cellular interstitial pneumonia in transbronchial lung biopsy, in addition to radiographic findings not typical for usual interstitial pneumonia, could expect a beneficial effect of steroids without undergoing surgical biopsy.
FasL and FADD delivery by a glioma-specific and cell cycle-dependent HSV-1 amplicon virus enhanced apoptosis in primary human brain tumors
Authors: Ivy A Ho, Wai H Ng, Paula Y Lam
Journal: Molecular Cancer (2010)

Glioblastoma multiforme is the most malignant cancer of the brain and is notoriously difficult to treat due to the highly proliferative and infiltrative nature of the cells. Herein, we explored the combination treatment of pre-established human glioma xenograft using multiple therapeutic genes whereby the gene expression is regulated by both cell-type and cell cycle-dependent transcriptional regulatory mechanism conferred by recombinant HSV-1 amplicon vectors.We demonstrated for the first time that Ki67-positive proliferating primary human glioma cells cultured from biopsy samples were effectively induced into cell death by the dual-specific function of the pG8-FasL amplicon vectors. These vectors were relatively stable and exhibited minimal cytotoxicity in vivo. Intracranial implantation of pre-transduced glioma cells resulted in better survival outcome when compared with viral vectors inoculated one week post-implantation of tumor cells, indicating that therapeutic efficacy is dependent on the viral spread and mode of viral vectors administration. We further showed that pG8-FasL amplicon vectors are functional in the presence of commonly used treatment regimens for human brain cancer. In fact, the combined therapies of pG8-FasL and pG8-FADD in the presence of temozolomide significantly improved the survival of mice bearing intracranial high-grade gliomas.Taken together, our results showed that the glioma-specific and cell cycle-dependent HSV-1 amplicon vector is potentially useful as an adjuvant therapy to complement the current gene therapy strategy for gliomas.
Native and aspirin-triggered lipoxins control innate immunity by inducing proteasomal degradation of TRAF6
Authors: Fabiana S. Machado, Lísia Esper, Alexandra Dias, Rajat Madan, YuanYuan Gu, David Hildeman, Charles N. Serhan, Christopher L. Karp, Júlio Aliberti
Journal: The Journal of Experimental Medicine (2008)

Innate immune signaling is critical for the development of protective immunity. Such signaling is, perforce, tightly controlled. Lipoxins (LXs) are eicosanoid mediators that play key counterregulatory roles during infection. The molecular mechanisms underlying LX-mediated control of innate immune signaling are of interest. In this study, we show that LX and aspirin (ASA)-triggered LX (ATL) inhibit innate immune signaling by inducing suppressor of cytokine signaling (SOCS) 2–dependent ubiquitinylation and proteasome-mediated degradation of TNF receptor–associated factor (TRAF) 2 and TRAF6, which are adaptor molecules that couple TNF and interleukin-1 receptor/Toll-like receptor family members to intracellular signaling events. LX-mediated degradation of TRAF6 inhibits proinflammatory cytokine production by dendritic cells. This restraint of innate immune signaling can be ablated by inhibition of proteasome function. In vivo, this leads to dysregulated immune responses, accompanied by increased mortality during infection. Proteasomal degradation of TRAF6 is a central mechanism underlying LX-driven immune counterregulation, and a hitherto unappreciated mechanism of action of ASA. These findings suggest a new molecular target for drug development for diseases marked by dysregulated inflammatory responses.
Changes in Transmural Central Venous Pressure in Man During Hyperventilation12
Authors: John W. Eckstein, William K. Hamilton
Journal: Journal of Clinical Investigation (1958)

We demonstrated that large amounts of blood shift from the forearm veins during hyperventilation (2). If this effect were generalized in the periphery of the body the volume of blood in the central venous reservoir might increase. An increase in pressure in the central veins would be evidence to support this suggestion. The fall in peripheral venous pressure which occurs during hyperventilation (2, 3), however, implies that central venous pressure also decreases. This makes our thesis less attractive. Still, the transmural pressure (4), the net pressure acting to distend the central veins, could increase during overbreathing if the pressure surrounding the veins (intrapleural pressure) decreased more than did the pressure within them. This study was undertaken to assess the nature and magnitude of changes in mean transmural central venous pressure during hyperventilation and to see whether the changes were consistent with our suggestion that blood shifts centrally during overbreathing.