Analysis of the HLA class I associated peptide repertoire in a hepatocellular carcinoma cell line reveals tumor-specific peptides as putative targets for immunotherapy

HLA class I molecules present peptides on the cell surface to CD8(+) T cells. The repertoire of peptides that associate to class I molecules represents the cellular proteome. Therefore, cells expressing different proteomes could generate different class I-associated peptide repertoires. A large number of peptides have been sequenced from HLA class I alleles, mostly from lymphoid cells. On the other hand, T cell immunotherapy is a goal in the fight against cancer, but the identification of T cell epitopes is a laborious task. Proteomic techniques allow the definition of putative T cell epitopes by the identification of HLA natural ligands in tumor cells. In this study, we have compared the HLA class I-associated peptide repertoire from the hepatocellular carcinoma (HCC) cell line SK-Hep-1 with that previously described from lymphoid cells. The analysis of the peptide pool confirmed that, as expected, the peptides from SK-Hep-1 derive from proteins localized in the same compartments as in lymphoid cells. Within this pool, we have identified 12 HLA class I peptides derived from HCC-related proteins. This confirms that tumor cell lines could be a good source of tumor associated antigens to be used, together with MS, to define putative epitopes for cytotoxic T cells from cancer patients.     

Irrigation infrastructure development in the Limarí Basin in Central Chile: implications for adaptation to climate variability and climate change

One option to deal with climate variability in agriculture is to build irrigation infrastructure, although this may lead to the overdevelopment of water resources, leading to ‘basin closure’. The Limarí Basin, in central north Chile, has relied on irrigation infrastructure over the last 30 years to increase water supply reliability and extend irrigated acreage, especially for permanent crops. This situation has reduced adaptation opportunities in the basin, which is currently experiencing a severe drought that, according to climate change projections, is expected to persist in the future, with important consequences for the sustainability of agriculture production.     

Sex Differences and Individual Differences in Cognitive Performance and Their Relationship to Endogenous Gonadal Hormones and Gonadotropins.

Sexually dimorphic cognitive performance in men (n=42) and women (n=42) was related to testosterone, estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, and sex hormone binding globulin, measured in 10-ml blood samples collected between 0900 and 1030 and, among women, during the follicular phase of the menstrual cycle. Significant sex differences favored men on spatial tasks (Mental Rotation and Judgment of Line Orientation) and on an inhibition task and favored women on a verbal task (category fluency). However, there were no significant relationships between any of the hormones and cognitive performance, suggesting that there are few, if any, consistent, substantial relationships between endogenous, nonfluctuating levels of gonadal hormones or gonadotropins and these cognitive abilities in men or women. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

No, It Is Not Possible to Be Schizophrenic Yet Neuropsychologically Normal.

Cognitive impairment is well documented in schizophrenia, though some reports have been interpreted to suggest that it is possible to have schizophrenia without neuropsychological impairment. The authors tested this by comparing the neuropsychological profiles of closely matched patients with schizophrenia and healthy comparison participants. Sixty-four patients with schizophrenia and 64 healthy comparison cases, matched to within 3 Full-Scale IQ points, were tested using the Wechsler Adult Intelligence Scale (3rd ed.; D. Wechsler, 1997b) and the Wechsler Memory Scale (3rd ed.; D. Wechsler, 1997c). Neuropsychological profiles for these groups were markedly different, with the group of patients with schizophrenia exhibiting performance deficits in memory and speeded visual processing but superior verbal comprehension and perceptual organization relative to the group of healthy comparison participants matched on Full-Scale IQ. Thus, scoring in the normal range does not preclude neuropsychological abnormality in schizophrenia, confirming that neuropsychological impairment is a core feature of the illness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Robust estimation of continuous nonlinear plants with discrete measurements

In this work the problem of designing a state estimator for completely or partially observable continuous nonlinear plants with discrete measurements is addressed. The combination of a geometric approach with a stability analysis yields an estimator design methodology with a nonlinear detectability condition susceptible of testing, a systematic estimator construction, a robust convergence criterion coupled with a simple tuning scheme, as well as a rationale to explain the interplay between sampling time, estimator gains, and estimator functioning. Comparing with the continuous measurement case where the convergence is attained by tuning the gain above a low limit, in the discrete measurement case the loss of information due to the measurement sampling increases the size of the lower gain limit, and imposes sampling time and high gain limits. The proposed methodology is applied to address the estimation problem of a class of solution homopolymerization reactors, and is tested with a methyl-methacrylate polymerization run taken from a previous extended Kalman filter implementation study with experimental data.     

The role of coping in the relationship between perceived racism and racism-related stress for Asian Americans: Gender differences.

On the basis of stress and coping theory, the authors examined coping as a mediator of the relationship between perceptions of racism and racism-related stress with a sample of Asian American college students (N = 336). Results indicated that coping mediated the relationship between racism and racism-related stress differentially by gender. The more that men perceived racism, the more likely they were to use support-seeking coping strategies that were associated with higher levels of racism-related stress. The more that women perceived racism, the more they used active coping strategies that were associated with higher levels of racism-related stress. The findings demonstrate how coping with racism differs for Asian Americans on the basis of gender. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Malignant Transformation of Giant Cell Tumour of Bone: A Review of Literature and the Experience of a Referral Centre

Giant cell tumour of bone (GCTB) is a benign, locally aggressive primary bone neoplasm that represents 5% of all bone tumours. The principal treatment approach is surgery. Although generally GCTB is considered only a locally aggressive disease, it can metastasise, and lung metastases occur in 1–9% of patients. To date, only the use of denosumab has been approved as medical treatment for GCTB. Even more rarely, GCTB undergoes sarcomatous transformation into a malignant tumour (4% of all GCTB), but history of this malignant transformation is unclear and unpredictable. Considering the rarity of the event, the data in the literature are few. In this review, we summarise published data of GCTB malignant transformation and we analyse three cases of malignant transformation of GCTB, evaluating histopathology, genetics, and radiological aspects. Despite the rarity of this event, we conclude that a strict follow up is recommended to detect early malignant transformation.     

Polygenic Risk of Hypertriglyceridemia Is Modified by BMI

Background: Genetic risk scores (GRSs) have partially improved the understanding of the etiology of moderate hypertriglyceridemia (HTG), which until recently was mainly assessed by secondary predisposing causes. The main objective of this study was to assess whether this variability is due to the interaction between clinical variables and GRS. Methods: We analyzed 276 patients with suspected polygenic HTG. An unweighted GRS was developed with the following variants: c.724C > G (ZPR1 gene), c.56C > G (APOA5 gene), c.1337T > C (GCKR gene), g.19986711A > G (LPL gene), c.107 + 1647T > C (BAZ1B gene) and g.125478730A > T (TRIB gene). Interactions between the GRS and clinical variables (body mass index (BMI), diabetes mellitus, diet, physical activity, alcohol consumption, age and gender) were evaluated. Results: The GRS was associated with triglyceride (TG) concentrations. There was a significant interaction between BMI and GRS, with the intensity of the relationship between the number of alleles and the TG concentration being greater in individuals with a higher BMI. Conclusions: GRS is associated with plasma TG concentrations and is markedly influenced by BMI. This finding could improve the stratification of patients with a high genetic risk for HTG who could benefit from more intensive healthcare interventions.