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Thousands of sieve tube exudate proteins (STEP) have now been identified and predicted to fulfill a diversity of functions. However, most STEPs should be considered putative, since methods to collect sieve tube exudates have many technical drawbacks, and advanced functional characterization will be required to distinguish contaminant from bonafide proteins, and determine the latter's location and activity in sieve elements (SE). One major challenge is to develop new approaches to elucidate the function of these SE proteins, which in turn, is expected to shed light on intriguing aspects of SE cell biology. [ABSTRACT FROM AUTHOR]

Insulin, secreted from pancreatic islets of Langerhans, is of critical importance in regulating glucose homeostasis. Defective insulin secretion and/or the inability of tissues to respond to insulin results in insulin resistance and to several metabolic and organ alterations. We have previously demonstrated that BAG3 regulates insulin secretion. Herein we explored the consequences of beta-cells specific BAG3 deficiency in an animal model. We generated a beta-cells specific BAG3 knockout mouse model. Glucose and insulin tolerance tests, proteomics, metabolomics, and immunohistochemical analysis were used to investigate the role of BAG3 in regulating insulin secretion and the effects of chronic exposure to excessive insulin release in vivo. Beta-cells specific BAG3 knockout results in primary hyperinsulinism due to excessive insulin exocytosis finally leading to insulin resistance. We demonstrate that resistance is mainly muscle-dependent while the liver remains insulin sensitive. The chronically altered metabolic condition leads in time to histopathological alterations in different organs. We observe elevated glycogen and lipid accumulation in the liver reminiscent of non-alcoholic fatty liver disease as well as mesangial matrix expansion and thickening of the glomerular basement membrane, resembling the histology of chronic kidney disease. Altogether, this study shows that BAG3 plays a role in insulin secretion and provides a model for the study of hyperinsulinemia and insulin resistance. • BAG3 is involved in insulin release. • Beta-Cells specific BAG3 knockout results in primary hyperinsulinism. • Chronic hyperinsulinemia leads to insulin resistance in this mouse model. • Beta-Cells loss of BAG3 deficient mice developed multiple organ alterations. [ABSTRACT FROM AUTHOR]

Phloem and xylem tissues are necessary for the allocation of nutrients and photoassimilates. However, how the long-distance transport of carbon (C) and nitrogen (N) is coordinated with the central metabolism is largely unknown. To better understand how the genetic and environmental factors influence C and N transport, we analysed the metabolite profiles of phloem exudates and xylem saps of five Arabidopsis thaliana accessions grown in low or non-limiting N supply. We observed that xylem saps were composed of 46 or 56% carbohydrates, 27 or 45% amino acids, and 5 or 13% organic acids in low or non-limiting N supply, respectively. In contrast, phloem exudates were composed of 76 or 86% carbohydrates, 7 or 18% amino acids, and 5 or 6% organic acids. Variation in N supply impacted amino acid, organic acid and sugar contents. When comparing low N and non-limiting N, the most striking differences were variations of glutamine, aspartate, and succinate abundance in the xylem saps and citrate and fumarate abundance in phloem exudates. In addition, we observed a substantial variation of metabolite content between genotypes, particularly under high N. The content of several organic acids, such as malate, citrate, fumarate, and succinate was affected by the genotype alone or by the interaction between genotype and N supply. This study confirmed that the response of the transport of nutrients in the phloem and the xylem to N availability is associated with the regulation of the central metabolism and could be an adaptive trait. [ABSTRACT FROM AUTHOR]

Background: Caloric restriction in obese diabetic patients quickly improves glucose control, independently from weight loss. However, the early effects of a very-low-calorie diet (VLCD) on insulin sensitivity and insulin secretion in morbidly obese patients with type 2 diabetes are still unclear. Objective: The objective was to study the relative contributions of insulin sensitivity, insulin secretion, or both to improvement in glucose metabolism, after 1 wk of caloric restriction, in severely obese diabetic patients. Design: Hyperglycemic clamps were performed in 14 severely obese (BMI, in kg/m2: >40) patients with type 2 diabetes in good glucose control (glycated hemoglobin < 7.5%) before and after 7 d of a VLCD (400 kcal/d). Results: The VLCD caused a 3.22 ± 0.56% weight loss (P < 0.001), 42.0% of which was fat loss, accompanied by decreases in fasting plasma glucose (P < 0.05) and triglycerides (P < 0.01). In parallel, the Disposition Index, which measures the body's capability to dispose of a glucose load, increased from 59.0 ± 6.3 to 75.5 ± 6.3 mL- min-1 • m-2 body surface area (P < 0.01), because of improvements in indexes of both first- and second-phase insulin secretion (P < 0.02), but with no changes in insulin sensitivity (P = 0.33). Conclusion: The marked improvement in metabolic profile, observed in severely obese patients with type 2 diabetes after a 7-d VLCD, was primarily due to the amelioration of β cell function, whereas no contribution of insulin sensitivity was shown. This trial was registered at www.clinicaltrials.gov as NCT01447524. [ABSTRACT FROM AUTHOR]

Debris flows, responsible for economic losses and occasionally casualties in the alpine region, are mainly triggered by heavy rains characterized by hourly peaks of varying intensity, depending on the features of the basin under consideration. By integrating a recent classification of alpine basins with the radar storm tracking method, an innovative early warning system called DEFENSE (DEbris Flows triggEred by storms - Nowcasting SystEm) was developed using a Geographical Information System (GIS). Alpine catchments were classified into three main classes based on the weathering capacity of the bedrock into clay or clay-like minerals, the amount of which, in unconsolidated material, directly influences the debris flow rheology, and thus the sedimentary processes, the alluvial fan architecture, as well as the triggering frequency and seasonal occurrence probability of debris flows. Storms were identified and tracked by processing weather radar observations; subsequently, rainfall intensities and storm severity were estimated over each classified basin. Due to rainfall threshold values determined for each basin class, based on statistical analysis of historical records, an automatic corresponding warning could be issued to municipalities. [ABSTRACT FROM AUTHOR]

Objective: Nonlymphoma-associated bcl-2/IgH rearrangements (NLABRs) are frequently amplified by PCR in blood of lymphoma-free subjects (LFS), but the temporal kinetics and phenotypic nature of NLABR-positive cells are unknown. To address these issues we prospectively monitored a panel of NLABR-positive LFS. Methods: LFS have been studied by nested PCR, real-time PCR, and DNA sequencing. Cell selection studies were also performed to define the nature of NLABR-bearing clones. Results: Of 125 donors, 16 (12.8%) were found to be bcl-2/IgH positive and were monitored at least every 6 months for a median time of 22 months (range 6–50). In half of the subjects the same NLABR detected initially was again reamplified at follow-up thrice or more. In 5, the same NLABR was constantly amplified in every follow-up sample. With a median follow-up of 22 months (range 9–50), no stable disappearance of a recurrent clone has been so far recorded. Real-time PCR indicated that persistent NLABR-positive clones are stable over time in the same subject. Cell separation studies indicate that NLABRs belong to CD19+, CD5−, CD23−, CD10+/− cells. Conclusions: Our results indicate that NLABR-positive clones are persistent populations phenotypically related to follicular lymphoma (FL). This suggests the existence of a FL-related clonal expansion of undetermined significance, which might be either a premalignant or a nonmalignant counterpart of FL. [Copyright &y& Elsevier]

Background Few studies in the literature have examined the effects of benzene on blood cells. Aim The aim of this study was to evaluate the possible correlation between the blood benzene levels and the blood cell counts. Materials and methods From a population of 2658 workers, we studied a group of 215 subjects. Each worker underwent blood sampling for the assessment of the blood benzene levels and the blood cell counts. The Mann–Whitney U test for two-mode variables and the Kruskal–Wallis test for more-than-two-mode variables were performed on all subjects. We estimated the Pearson correlation index between the variables in the total sample and the subgroups divided according to sex, the smoking habit, and job. After the main confounding factors were evaluated, multiple linear regression was performed on both the total sample and the subgroups. Results A significant inverse correlation was found among the blood benzene levels and the white blood cells, lymphocytes, and neutrophils in traffic policemen, motorcyclists, and other outdoor workers. We did not find any significant correlation with any other parameters of blood cell count. Discussion and conclusions Our results, which must be considered preliminary, indicate that increased blood benzene levels in outdoor workers lead to decreased counts of white blood cells, neutrophils, and lymphocytes, because of possible immune effects. These are worth investigating in the future by specific immune tests. [ABSTRACT FROM AUTHOR]

Abstract: Molecular remission (MR) is associated with improved outcome in mantle cell lymphoma (MCL). If MR is not achieved, patients are at high risk of relapse. We retrospectively describe the molecular and clinical follow-ups of 4 patients with molecular relapses (M-rels) who were treated with rituximab. The 4 patients received rituximab-supplemented, high-dose sequential chemotherapy and autologous stem cell transplantation as induction treatment and achieved clinical remission and MR. M-rel was defined as polymerase chain reaction (PCR) positivity in 2 consecutive samples in the absence of clinical relapse. M-rels occurred at 3, 6, 39, and 52 months and were always confirmed by direct sequencing of the clonal rearrangement. Minimal residual disease was monitored by qualitative and real-time quantitative PCR. All patients received 4 courses of rituximab, with 2 additional infusions if PCR positivity remained. After 4-6 courses of rituximab, all patients re-entered MR. No clinical relapses were recorded at 3, 6, 18, and 62 months from treatment, although 1 patient had a second M-rel that was sensitive to rituximab. Our results indicate that rituximab is active against residual MCL cells and suggest that molecularly tailored maintenance therapy needs to be investigated in clinical trials. [Copyright &y& Elsevier]