Condensed tannins in the diets of primates: a matter of methods?

To understand the ways in which condensed tannins (CT) affect primate diet selection and nutritional status, correct measurements are essential. In the majority of studies of the CT contents of primate foods, a tannin source such as "quebracho" is used to standardize CT assays, but the CT in quebracho tannin may not be similar to those in the plants of interest. We investigated how the choice of standard to calibrate CT assays affects the estimation of CT in the diets of mountain gorillas (Gorilla beringei). We purified the CT from gorilla foods and compared the actual amounts of CT in the foods with estimates produced by using the quebracho tannin. When quebracho was used, the estimates of CT contents of gorilla foods were, on average, 3.6 times the actual content of CT so that the amounts in frequently eaten gorilla foods were substantially overestimated. The overestimation for a given plant could not be predicted reliably and the ranking of plants by tannin content differed according to the standard used. Our results demonstrate that accurate measurements of CT necessitate the use of tannins purified from the plant species of interest. A reevaluation of primatology studies using interspecific comparisons of tannin content will provide new insights into primate food selection and nutritional ecology.     

Transfer of tilt after-effects between second-order cues

Second-order cues are visual stimuli that are detectable by human observers, without eliciting a peak in Fourier energy that corresponds to their perceptual properties. The most commonly studied exemplars of second-order cues are those defined by modulation of local contrast (CM). It is widely accepted that such cues are initially detected separately from first-order, luminance modulated (LM), cues. However, after-effects have been shown to transfer between first- and second-order cues (LM and CM, respectively). This suggests the existence of a late link in the mechanisms that subserve their processing. To extend the investigation of the mechanisms for processing second-order cues we consider cues defined by modulations in local orientation (OM). Using a tilt-after-effect (TAE) paradigm, we found partial transfer of adaptation between LM and OM cues, confirming the presence of a link between first and second-order cues. Furthermore, we found a partial transfer of TAE between OM and CM cues. These results suggest that, at or before the site of adaptation, information from all visual cues is combined. However, as transfer of adaptation is below 100% in all cases, this is only a partial integration of information.     

THE BIOSYNTHESIS OF C13 COMPOUNDS : I. THE BIOSYNTHESIS OF C13-LABELED STARCH

1. Starch, containing 7.05 atom per cent C¹³ excess has been produced in the mesophyll cells of bean leaves, starting with C¹³O₂ containing 7.26 atom per cent C¹³ excess. Approximately 67 per cent of the C¹³ taken up by the leaves was determined in the starch fraction. 2. The soluble carbohydrate, containing 6.72 atom per cent C¹³ excess, accounts for approximately 23 per cent of the C¹³ taken up by the leaves. The remainder was principally in the coarse tissue fragments fraction (9.73 per cent of the C¹³ utilized). 3. The apparatus and procedures used in this experiment are described.     

Growth factors and glucose homeostasis in diabetic rats: effects of exercise training

To investigate the alterations of glucose homeostasis and variables of the insulin‐like growth factor‐1 (IGF‐1) growth system in sedentary and trained diabetic (TD) rats, Wistar rats were divided into sedentary control (SC), trained control (TC), sedentary diabetic (SD), and TD groups. Diabetes was induced by Alloxan (35 mg kg^?1 b.w.). Training program consisted of swimming 5 days week^?1, 1 h day^?1, during 8 weeks. Rats were sacrificed and blood was collected for determinations of serum glucose, insulin, growth hormone (GH), IGF‐1, and IGF binding protein‐3 (IGFBP‐3). Muscle and liver were removed to evaluate glycogen content. Cerebellum was extracted to determinate IGF‐1 content. Diabetes decreased serum GH, IGF‐1, IGFBP‐3, liver glycogen, and cerebellum IGF‐1 peptide content in baseline condition. Physical training recovered liver glycogen and increased serum and cerebellum IGF‐1 peptide in diabetic rats. Physical training induces important metabolic and hormonal alterations that are associated with an improvement in glucose homeostasis and serum and cerebellum IGF‐1 concentrations. Copyright © 2009 John Wiley & Sons, Ltd.     

Cryoprotectants and Extreme Freeze Tolerance in a Subarctic Population of the Wood Frog

Wood frogs (Rana sylvatica) exhibit marked geographic variation in freeze tolerance, with subarctic populations tolerating experimental freezing to temperatures at least 10-13 degrees Celsius below the lethal limits for conspecifics from more temperate locales. We determined how seasonal responses enhance the cryoprotectant system in these northern frogs, and also investigated their physiological responses to somatic freezing at extreme temperatures. Alaskan frogs collected in late summer had plasma urea levels near 10 μmol ml^-1, but this level rose during preparation for winter to 85.5 ± 2.9 μmol ml^-1 (mean ± SEM) in frogs that remained fully hydrated, and to 186.9 ± 12.4 μmol ml^-1 in frogs held under a restricted moisture regime. An osmolality gap indicated that the plasma of winter-conditioned frogs contained an as yet unidentified osmolyte(s) that contributed about 75 mOsmol kg^-1 to total osmotic pressure. Experimental freezing to –8°C, either directly or following three cycles of freezing/thawing between –4 and 0°C, or –16°C increased the liver’s synthesis of glucose and, to a lesser extent, urea. Concomitantly, organs shed up to one-half (skeletal muscle) or two-thirds (liver) of their water, with cryoprotectant in the remaining fluid reaching concentrations as high as 0.2 and 2.1 M, respectively. Freeze/thaw cycling, which was readily survived by winter-conditioned frogs, greatly increased hepatic glycogenolysis and delivery of glucose (but not urea) to skeletal muscle. We conclude that cryoprotectant accrual in anticipation of and in response to freezing have been greatly enhanced and contribute to extreme freeze tolerance in northern R. sylvatica.     

Prediction of Recurrence and Survival for Triple-Negative Breast Cancer (TNBC) by a Protein Signature in Tissue Samples

To date, there is no available targeted therapy for patients who are diagnosed with triple-negative breast cancers (TNBC). The aim of this study was to identify a new specific target for specific treatments. Frozen primary tumors were collected from 83 adjuvant therapy-naive TNBC patients. These samples were used for global proteome profiling by iTRAQ-OFFGEL-LC-MS/MS approach in two series: a training cohort (n = 42) and a test set (n = 41). Patients who remains free of local or distant metastasis for a minimum of 5 years after surgery were classified in the no-relapse group; the others were in the relapse group. OPLS and Kaplan–Meier analyses were performed to select candidate markers, which were validated by immunohistochemistry. Three proteins were identified in the training set and validated in the test set by Kaplan–Meier method and immunohistochemistry (IHC): TrpRS as a good prognostic markers and DP and TSP1 as bad prognostic markers. We propose the establishment of an IHC test to calculate the score of TrpRS, DP, and TSP1 in TNBC tumors to evaluate the degree of aggressiveness of the tumors. Finally, we propose that DP and TSP1 could provide therapeutic targets for specific treatments.Triple-negative breast cancers (TNBC)¹ are defined by a lack of expression of estrogen (ER), progesterone (PR), and HER2/neu receptors and account for about 15% of all breast cancers. This subtype is associated with poor prognosis (1) in terms of distant free survival (DFS) and overall survival (OS), and to date, there is no clinically available targeted therapy for patients diagnosed with TNBC. Because of the absence of specific treatment guidelines for this group of patients, TNBC are managed with standard adjuvant chemotherapy (2), which, however, seems to be less effective in those cancers. In order to improve survival, it is important to determine new specific-targeted treatment.A proteomic analysis has several inherent advantages over a genomic approach in that measured mRNA levels do not necessarily correlate to corresponding protein levels. In addition, protein detection is probably also more reflective of the tumor microenvironment. Several proteomic studies have been conducted on TNBC (3–5), but no proteomic study was conducted on large cohorts including the clinical outcome of the patients, except a recent comparative proteome analysis that identified a 11-protein signature for aggressive TNBC in a large cohort of 93 microdissected tumors (6). Although microdissection was necessary to elucidate the contribution of TNBC cells, it did not reflect the tumor with its microenvironment that is increasingly described as fundamental to explain the tumor outcome. Thus, it is now recognized that carcinomas derive from phenomena that occur in tissues, not in individual cancer cells. From this perspective, the microenvironment becomes an integral, essential part of the tumor (7, 8). In this context, taking into account the tumor microenvironment, we investigated a cohort of 83 TNBC samples without microdissection by a quantitative proteomic approach using iTRAQ labeling. Based on clinical data, we established a protein signature of the most aggressive tumors. From these differentially expressed proteins, some of them appeared to be potential therapeutic targets.     

A Role for the Chaperone Complex BAG3-HSPB8 in Actin Dynamics,Spindle Orientation and Proper Chromosome Segregation during Mitosis

The co-chaperone BAG3, in complex with the heat shock protein HSPB8, plays a role in protein quality control during mechanical strain. It is part of a multichaperone complex that senses damaged cytoskeletal proteins and orchestrates their seclusion and/or degradation by selective autophagy. Here we describe a novel role for the BAG3-HSPB8 complex in mitosis, a process involving profound changes in cell tension homeostasis. BAG3 is hyperphosphorylated at mitotic entry and localizes to centrosomal regions. BAG3 regulates, in an HSPB8-dependent manner, the timely congression of chromosomes to the metaphase plate by influencing the three-dimensional positioning of the mitotic spindle. Depletion of BAG3 caused defects in cell rounding at metaphase and dramatic blebbing of the cortex associated with abnormal spindle rotations. Similar defects were observed upon silencing of the autophagic receptor p62/SQSTM1 that contributes to BAG3-mediated selective autophagy pathway. Mitotic cells depleted of BAG3, HSPB8 or p62/SQSTM1 exhibited disorganized actin-rich retraction fibres, which are proposed to guide spindle orientation. Proper spindle positioning was rescued in BAG3-depleted cells upon addition of the lectin concanavalin A, which restores cortex rigidity. Together, our findings suggest the existence of a so-far unrecognized quality control mechanism involving BAG3, HSPB8 and p62/SQSTM1 for accurate remodelling of actin-based mitotic structures that guide spindle orientation.