Functional Inactivation of Drosophila GCK Orthologs Causes Genomic Instability and Oxidative Stress in a Fly Model of MODY-2

Maturity-onset diabetes of the young (MODY) type 2 is caused by heterozygous inactivating mutations in the gene encoding glucokinase (GCK), a pivotal enzyme for glucose homeostasis. In the pancreas GCK regulates insulin secretion, while in the liver it promotes glucose utilization and storage. We showed that silencing the Drosophila GCK orthologs Hex-A and Hex-C results in a MODY-2-like hyperglycemia. Targeted knock-down revealed that Hex-A is expressed in insulin producing cells (IPCs) whereas Hex-C is specifically expressed in the fat body. We showed that Hex-A is essential for insulin secretion and it is required for Hex-C expression. Reduced levels of either Hex-A or Hex-C resulted in chromosome aberrations (CABs), together with an increased production of advanced glycation end-products (AGEs) and reactive oxygen species (ROS). This result suggests that CABs, in GCK depleted cells, are likely due to hyperglycemia, which produces oxidative stress through AGE metabolism. In agreement with this hypothesis, treating GCK-depleted larvae with the antioxidant vitamin B6 rescued CABs, whereas the treatment with a B6 inhibitor enhanced genomic instability. Although MODY-2 rarely produces complications, our data revealed the possibility that MODY-2 impacts genome integrity.     

Investigating the acceptability of behavioral interventions in applied conjoint behavioral consultation: Moving from analog conditions to naturalistic settings.

Whereas there exists a vast literature investigating consumer satisfaction ratings of various behavioral interventions, the majority of these studies have been limited to analogue conditions, which may compromise utility and generalization. Additionally, most research has failed to explore multiple-source, multiple-setting data in the investigation of treatment acceptability. This study investigated parent, teacher, and child treatment acceptability ratings derived from field-based conjoint behavioral consultation cases. Data indicate that overall, 67 parents (aged 23-54 yrs), 67 teachers (aged 22-57 yrs), and 67 children (aged 5-15 yrs) rated conjoint behavioral consultation-based behavioral interventions as very to highly acceptable. For parents, interventions with a reductive component were rated as more acceptable than interventions using both positive and negative components; no significant differences were found among teacher and child group ratings. For teachers, there was a positive relationship between (a) intervention complexity and treatment acceptability ratings and (b) problem severity ratings and treatment acceptability ratings... (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Fermi–Bose Correspondence and Bose–Einstein Condensation in the Two-Dimensional Ideal Gas

The ideal uniform two-dimensional (2D) Fermi and Bose gases are considered both in the thermodynamic limit and the finite case. We derive May's Theorem, viz. the correspondence between the internal energies of the Fermi and Bose gases in the thermodynamic limit. This results in both gases having the same heat capacity. However, as we shall show, the thermodynamic limit is never truly reached in two dimensions and so it is essential to consider finite-size effects. We show in an elementary manner that for the finite 2D Bose gas, a pseudo-Bose–Einstein condensate forms at low temperatures, incompatible with May's Theorem. The two gases now have different heat capacities, dependent on the system size and tending to the same expression in the thermodynamic limit.     

Becker muscular dystrophy with bundle branch reentry ventricular tachycardia

This report describes a case of Becker muscular dystrophy presenting with recurrent symptomatic wide complex tachycardia. Electrophysiologic testing demonstrated the mechanism to be bundle branch reentry ventricular tachycardia. It is important to consider this potential mechanism in patients with ventricular arrhythmias who have this particular clinical entity, since radiofrequency catheter ablation can represent a curative treatment.     

The application of nonlinear structures to the reconstruction ofbinary signals

The problem of reconstructing digital signals which have been passed through a dispersive channel and corrupted with additive noise is discussed. The problems encountered by linear equalizers under adverse conditions on the signal-to-noise ratio and channel phase are described. By considering the equalization problem as a geometric classification problem the authors demonstrate how these difficulties can be overcome by utilizing nonlinear classifiers as channel equalizers. The manner in which neural networks can be utilized as adaptive channel equalizers is described, and simulation results which suggest that the neural network equalizers offer a performance which exceeds that of the linear structures, particularly in the high-noise environment, are presented     

On the Auditory Modality Superiority Effect in Serial Recall: Separating Input and Output Factors.

The modality effect in immediate recall refers to superior recall of the last few items within lists presented in spoken as opposed to printed form. The locus of this well-known effect has been unclear. N. Cowan, J. S. Saults, E. M. Elliott, and M. Moreno (2002) introduced a new method to distinguish between the effects of input serial position, output serial position, and the number of items yet to be recalled and found that large modality effects occurred only in conditions in which delay and interference at output (from items already recalled) was high. The authors replicated that finding, even when the response period included output interference acoustically similar to the spoken stimuli to be recalled. However, the authors found that output delay and interference act only by lowering the level of performance to a more sensitive range. The modality effect thus originates during encoding of the list to be recalled, not during output. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Constraints on CD4 recovery postchemotherapy in adults: thymic insufficiency and apoptotic decline of expanded peripheral CD4 cells

To examine the mechanisms of CD4 reconstitution in an adult population, lymphocyte repopulation was assessed following dose-intense chemotherapy in 25 breast cancer patients, ages 33 to 69 years. Chemotherapy resulted in a greater than 60% reduction in total CD4 T cells and, in particular, a greater than 90% loss of the CD45RA+ CD4 cells. CD4 recovery was protracted, achieving less than 50% of pretreatment levels after 12 to 14 months. Two facets of the CD4 recovery were notable. First, generation of CD45RA+ CD4 cells played only a minor role in the first year, suggesting that thymic production was not the main route of CD4 regeneration. Indeed, recovery of CD45RA+ CD4 cell levels remained limited in half of the patients even after 2 years. Second, expansion of the mature peripheral CD4 cells (CD45RO+) remaining after chemotherapy was the main source of early CD4 repopulation, peaking at 3 to 6 months postchemotherapy. This expansion was limited in duration, however, and was followed by a secondary decline, such that the total CD45RO+ CD4 levels at 9 to 12 months were lower than at 6 months. When stimulated by mitogens, an increased susceptibility to apoptosis was observed in postchemotherapy CD4 cells as compared with those from normal donors. The elevated expression of markers such as HLA-DR during chemotherapy and for several months postchemotherapy is consistent with the presence of an activated T-cell population. CD4 apoptotic frequency correlated with the frequency of HLA-DR expression on T cells. Thus, CD4 recovery is constrained in adults by a limited thymic regenerative capacity and by an increased susceptibility to apoptosis within the expanding peripheral CD4 population.     

Timed reactions to an object in apparent motion: evidence on Cartesian and non-Cartesian perceptual hypotheses

In three experiments on apparent motion, subjects were to press a computer key as quickly as possible either when the apparently moving stimulus passed the midpoint of its trajectory or when it reached the endpoint. If motion is perceived as a trajectory through a series of spatial locations, and if this type of percept is the basis of deliberate responding (assumptions that can be considered Cartesian in origin), then reaction times should be faster to the midpoint than to the endpoint. In contrast to these assumptions, there was no difference between reaction times to these two points. Alternative accounts of the results are discussed.     

MMP1 and MMP11 Expression in Peripheral Blood Mononuclear Cells upon Their Interaction with Breast Cancer Cells and Fibroblasts

Tumor-infiltrating immune cells phenotype is associated with tumor progression. However, little is known about the phenotype of the peripheral blood mononuclear cells (PBMC) from breast cancer patients. We investigated MMP1 and MMP11 expression in PBMC from breast cancer patients and we analyzed gene expression changes upon their interaction with cancer cells and cancer-associated fibroblasts (CAF). We measured the impact of PBMC on proinflammatory gene expression in breast cancer cells, normal fibroblast (NF), and CAF and the impact on proliferation and invasiveness capacity of breast cancer cells. Gene expression of MMP1 and MMP11 in PBMC from breast cancer patients (n = 54) and control (n = 28); expression of IL1A, IL6, IL17, IFNβ, and NFĸB in breast cancer cell lines (MCF-7 and MDA-MB-231); and, additionally, IL10 and MMP11 in CAF and NF were analyzed by qRT-PCR before and after co-culture. Our results show the existence of a subpopulation of breast cancer patients (25.9%) with very high levels of MMP11 gene expression in PBMC. Also, gene expression of MMP1 and MMP11 increases in PBMC after co-culture with breast cancer cell lines, NF or CAF. PBMC from healthy or breast cancer patients induce an increased proliferation rate on MCF-7 and an increased invasiveness capacity of MDA-MB-231. Finally, we show a differential expression profile of inflammatory genes in NF and CAF when co-cultured with control or breast cancer PBMC. We have observed that MMPs’ expression in PBMC is regulated by the microenvironment, while the expression of inflammatory genes in NF or CAF is differentially regulated by PBMC. These findings confirm the importance of the crosstalk between stromal cells and suggest that PBMC would play a role in promoting aggressive tumor behavior.