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排序方式: 共有337条查询结果,搜索用时 15 毫秒
91.
Juan L. Trincado Marina Reixachs-Sol Judith Prez-Granado Tim Fugmann Ferran Sanz Jun Yokota Eduardo Eyras 《PLoS computational biology》2021,17(9)
Immunotherapies provide effective treatments for previously untreatable tumors and identifying tumor-specific epitopes can help elucidate the molecular determinants of therapy response. Here, we describe a pipeline, ISOTOPE (ISOform-guided prediction of epiTOPEs In Cancer), for the comprehensive identification of tumor-specific splicing-derived epitopes. Using RNA sequencing and mass spectrometry for MHC-I associated proteins, ISOTOPE identified neoepitopes from tumor-specific splicing events that are potentially presented by MHC-I complexes. Analysis of multiple samples indicates that splicing alterations may affect the production of self-epitopes and generate more candidate neoepitopes than somatic mutations. Although there was no difference in the number of splicing-derived neoepitopes between responders and non-responders to immune therapy, higher MHC-I binding affinity was associated with a positive response. Our analyses highlight the diversity of the immunogenic impacts of tumor-specific splicing alterations and the importance of studying splicing alterations to fully characterize tumors in the context of immunotherapies. ISOTOPE is available at https://github.com/comprna/ISOTOPE. 相似文献
92.
Elaboration of heparin-protein-binding interactions is necessary to understand how heparin modulates protein function. The heparin-binding domain of some proteins is postulated to be a helix structure which presents a surface of high positive charge density. Thus, a synthetic 19-residue peptide designed to be alpha-helical in character was synthesized, and its interaction with heparin was studied. The peptide was shown to be 75% helix by circular dichroism (CD) spectrometry in neutral pH buffer (at 2 degrees C); helicity increased to nearly 85% under high ionic strength conditions or to nearly 100% in 75% ethanol. Increasing the temperature of the solution caused a change in the spectral envelope consistent with a coil transition of the peptide. The midpoint of the transition (i.e., the temperature at which the helix content was determined to be 50%) was 25 degrees C, and the determined van't Hoff enthalpy change (delta HvH) was 3.2 kcal/mol of peptide. By CD, heparin increases the helix content of the peptide to 100% and increases the apparent thermal stability of the peptide by about 1 kcal/mol. The melting point for the helix/coil transition of the heparin-peptide complex was 50 degrees C. The thermal coefficient of the transition (approximately 300 deg.cm2.dmol-1.degree C-1) was essentially the same for the peptide alone or the peptide-heparin complex. Dissociation of the complex under high ionic strength conditions was also observed in the CD experiment. Biological assays showed less heparin-binding activity than expected (micromolar KD values), but this was attributed to the absence of critical lysyl residues in the peptide.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
93.
Jaime Feliu Antonieta Salud Maria J. Safont Carlos García-Girón Jorge Aparicio Ferran Losa Carlos Bosch Pilar Escudero Enrique Casado Monica Jorge Uriel Bohn Ramon Pérez-Carrión Alberto Carmona Ana B. Custodio Joan Maurel 《PloS one》2015,10(1)
Background
Studies suggest a relationship between hypertension and outcome in bevacizumab-treated patients with metastatic colorectal cancer (mCRC). We performed a retrospective analysis of two phase II studies (BECA and BECOX) to determine if hypertension and proteinuria predict outcome in elderly patients with mCRC treated with bevacizumab.Patients and Methods
Patients ≥70 years of age received either capecitabine 1250 mg/m2 bid days 1–14 + bevacizumab 7.5 mg/kg day 1 every 21 days (BECA study) or capecitabine 1000 mg/m2 bid days 1–14 with bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m2 day 1 (BECOX study). The primary objective was to correlate hypertension and proteinuria with overall response rate (ORR), time to progression (TTP) and overall survival (OS). Secondary objectives included identification of risk factors associated with the development of hypertension and proteinuria and determining whether development of hypertension or proteinuria in the first 2 cycles was related to ORR, disease-control rate (DCR), TTP or OS.Results
In total, 127 patients (median age 75.5 years) were included in the study. Hypertension correlated with DCR and OS; proteinuria correlated with ORR and DCR. Proteinuria or hypertension in the first 2 cycles did not correlate with efficacy. Risk factors for hypertension were female gender (odds ratio [OR] 0.241; P = 0.011) and more bevacizumab cycles (OR 1.112; P = 0.002); risk factors for proteinuria were diabetes (OR 3.869; P = 0.006) and more bevacizumab cycles (OR 1.181; P<0.0001). Multivariate analysis identified as having prognostic value: baseline lactate dehydrogenase, haemoglobin, number of metastatic lesions and DCR.Conclusion
This analysis of two phase II studies suggests that hypertension is significantly correlated with OS but not with ORR and TTP, whereas proteinuria is correlated with ORR but not with OS and TTP. Both hypertension and proteinuria are associated with the duration of bevacizumab treatment and do not represent an independent prognostic factor. 相似文献94.
Olivier Lambert Alberto Collareta Walter Landini Klaas Post Benjamin Ramassamy Claudio Di Celma Mario Urbina Giovanni Bianucci 《Proceedings. Biological sciences / The Royal Society》2015,282(1815)
Although modern beaked whales (Ziphiidae) are known to be highly specialized toothed whales that predominantly feed at great depths upon benthic and benthopelagic prey, only limited palaeontological data document this major ecological shift. We report on a ziphiid–fish assemblage from the Late Miocene of Peru that we interpret as the first direct evidence of a predator–prey relationship between a ziphiid and epipelagic fish. Preserved in a dolomite concretion, a skeleton of the stem ziphiid Messapicetus gregarius was discovered together with numerous skeletons of a clupeiform fish closely related to the epipelagic extant Pacific sardine (Sardinops sagax). Based on the position of fish individuals along the head and chest regions of the ziphiid, the lack of digestion marks on fish remains and the homogeneous size of individuals, we propose that this assemblage results from the death of the whale (possibly via toxin poisoning) shortly after the capture of prey from a single school. Together with morphological data and the frequent discovery of fossil crown ziphiids in deep-sea deposits, this exceptional record supports the hypothesis that only more derived ziphiids were regular deep divers and that the extinction of epipelagic forms may coincide with the radiation of true dolphins. 相似文献
95.
96.
Sabrina Llop Karin Engstr?m Ferran Ballester Elisa Franforte Ayman Alhamdow Federica Pisa Janja Snoj Tratnik Datja Mazej Mario Murcia Marisa Rebagliato Mariona Bustamante Jordi Sunyer Αikaterini Sofianou-Katsoulis Alexia Prasouli Eleni Antonopoulou Ioanna Antoniadou Sheena Nakou Fabio Barbone Milena Horvat Karin Broberg 《PloS one》2014,9(5)
Background
The genetic background may influence methylmercury (MeHg) metabolism and neurotoxicity. ATP binding cassette (ABC) transporters actively transport various xenobiotics across biological membranes.Objective
To investigate the role of ABC polymorphisms as modifiers of prenatal exposure to MeHg.Methods
The study population consisted of participants (n = 1651) in two birth cohorts, one in Italy and Greece (PHIME) and the other in Spain (INMA). Women were recruited during pregnancy in Italy and Spain, and during the perinatal period in Greece. Total mercury concentrations were measured in cord blood samples by atomic absorption spectrometry. Maternal fish intake during pregnancy was determined from questionnaires. Polymorphisms (n = 5) in the ABC genes ABCA1, ABCB1, ABCC1 and ABCC2 were analysed in both cohorts.Results
ABCB1 rs2032582, ABCC1 rs11075290, and ABCC2 rs2273697 modified the associations between maternal fish intake and cord blood mercury concentrations. The overall interaction coefficient between rs2032582 and log2-transformed fish intake was negative for carriers of GT (β = −0.29, 95%CI −0.47, −0.12) and TT (β = −0.49, 95%CI −0.71, −0.26) versus GG, meaning that for a doubling in fish intake of the mothers, children with the rs2032582 GG genotype accumulated 35% more mercury than children with TT. For rs11075290, the interaction coefficient was negative for carriers of TC (β = −0.12, 95%CI −0.33, 0.09), and TT (β = −0.28, 95%CI −0.51, −0.06) versus CC. For rs2273697, the interaction coefficient was positive when combining GA+AA (β = 0.16, 95%CI 0.01, 0.32) versus GG.Conclusion
The ABC transporters appear to play a role in accumulation of MeHg during early development. 相似文献97.
B. Lovern L.A. Stroud N.A. Ferran S.L. Evans R.O. Evans C.A. Holt 《Computer methods in biomechanics and biomedical engineering》2013,16(6):803-809
The shoulder complex has a larger range of motion (ROM) than any other joint complex in the human body, leaving it prone to numerous injuries. Objective kinematic analysis could yield useful functional insights that may assist clinical practice. Non-invasive optoelectronic motion analysis techniques have been used to assess the shoulders of five healthy subjects performing ROM tasks and 10 functional tasks of daily living. The four most demanding tasks – touching the side and back of the head, brushing the opposite side of the head, lifting an object to shoulder height and lifting an object to head height, required 78%, 60%, 61% and 71%, respectively, of the glenohumeral elevation necessary for full abduction in the scapular plane for the 10 shoulders. This has implications for clinical practice where maximum arm elevation is commonly used to determine a patient's ability to return to work and other everyday activities. 相似文献
98.
99.
In the exploration of the relationships between ethnicity, national identity, and symbolic building of the region, this article deals with a key issue: the achievements and limitations of the assimilation of culturally heterogeneous populations by European nation-states. The modern Spanish national identity (at times shown as purely political) has included and still includes cultural elements (above all, the spread of the Spanish language). This meant that the ethnicity of the Valencians (a population with autonomous political structures until their violent destruction in 1707) had to be redefined as a regional identity in order to avoid coming into conflict with national identity. This re-working excluded the Catalan language, spoken by most of the inhabitants of the region, from the political sphere. In the long term, this cultural characteristic became stigmatized, which favoured its undercommunication to the extent that a process of language shift was initiated. This case study highlights the historical analysis of ethnic identity and the instability of its integration into national structures. 相似文献
100.
Alexandre Martinez-Castillo Pablo Quirós Ferran Navarro Elisenda Miró Maite Muniesa 《Applied and environmental microbiology》2013,79(16):4862-4868
Shiga toxin-converting bacteriophages (Stx phages) carry the stx gene and convert nonpathogenic bacterial strains into Shiga toxin-producing bacteria. Previous studies have shown that high densities of free and infectious Stx phages are found in environments polluted with feces and also in food samples. Taken together, these two findings suggest that Stx phages could be excreted through feces, but this has not been tested to date. In this study, we purified Stx phages from 100 fecal samples from 100 healthy individuals showing no enteric symptoms. The phages retrieved from each sample were then quantified by quantitative PCR (qPCR). In total, 62% of the samples carried Stx phages, with an average value of 2.6 × 104 Stx phages/g. This result confirms the excretion of free Stx phages by healthy humans. Moreover, the Stx phages from feces were able to propagate in enrichment cultures of stx-negative Escherichia coli (strains C600 and O157:H7) and in Shigella sonnei, indicating that at least a fraction of the Stx phages present were infective. Plaque blot hybridization revealed lysis by Stx phages from feces. Our results confirm the presence of infectious free Stx phages in feces from healthy persons, possibly explaining the environmental prevalence observed in previous studies. It cannot be ruled out, therefore, that some positive stx results obtained during the molecular diagnosis of Shiga toxin-producing Escherichia coli (STEC)-related diseases using stool samples are due to the presence of Stx phages. 相似文献