Transient Responses to Rapid Changes in Mean and Variance in Spiking Models

The mean input and variance of the total synaptic input to a neuron can vary independently, suggesting two distinct information channels. Here we examine the impact of rapidly varying signals, delivered via these two information conduits, on the temporal dynamics of neuronal firing rate responses. We examine the responses of model neurons to step functions in either the mean or the variance of the input current. Our results show that the temporal dynamics governing response onset depends on the choice of model. Specifically, the existence of a hard threshold introduces an instantaneous component into the response onset of a leaky-integrate-and-fire model that is not present in other models studied here. Other response features, for example a decaying oscillatory approach to a new steady-state firing rate, appear to be more universal among neuronal models. The decay time constant of this approach is a power-law function of noise magnitude over a wide range of input parameters. Understanding how specific model properties underlie these response features is important for understanding how neurons will respond to rapidly varying signals, as the temporal dynamics of the response onset and response decay to new steady-state determine what range of signal frequencies a population of neurons can respond to and faithfully encode.     

A betasatellite-encoded protein regulates key components of gene silencing system in plants

Small circular single-stranded DNA satellites, called betasatellites, have been found in association with some monopartite begomovirus infections. The Cotton leaf curl Multan betasatellite (CLCuMuB) is known to influence symptom induction in cotton leaf curl disease. CLCuMuB contains a single gene, βC1, whose product is a pathogenicity determinant and a suppressor of RNA silencing. Although induction of RNA silencing by RNA and DNA viruses has been well documented in plants, the interactions between betasatellites and the host’s silencing machinery remain poorly understood. In this study, the transgenic expression of βC1 from CLCuMuB in Arabidopsis thaliana plants produced severe developmental abnormalities, which resembled those produced by mutations in the key genes of the gene silencing pathway. Analysis of transgenic plants expressing CLCuMuB βC1 using real-time PCR showed that the expression levels of both AGO1 and DCL1 genes were significantly increased. In contrast, the expression of HEN1 gene in the βC1-expressing leaf tissues was similar to that of wild-type plants. The CLCuMuB βC1 protein was found to physically interact with the AGO1 protein in a yeast two-hybrid system. It is possible that specific targeting of the gene silencing key components by the CLCuMuB βC1 inhibits the RNA silencing-based host defence.     

The impact of renin–angiotensin system,angiotensin І converting enzyme (insertion/deletion), and angiotensin ІІ type 1 receptor (A1166C) polymorphisms on breast cancer survival in Iran

Introduction

Several proteins of renin–angiotensin system (RAS) have been implicated in the process of growth promotion or inhibition of breast tissue and cancer cells. This study aimed to investigate the association between angiotensin I converting enzyme (ACE) insertion/deletion (I/D) and angiotensin receptor-1 (AGTR1) A1166C polymorphisms and survival of 110 women with breast cancer.

Materials and methods

The I/D and A1166C polymorphisms were evaluated by using Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) in 110 breast cancer patients who had been treated between 2007 and 2009. Genomic DNA was extracted from a Formalin-Fixed Paraffin-Embedded (FFPE) tissue of breast cancer sample blocks. All the potential clinical and pathological prognostic variables were analyzed to establish the impact of I/D and A1166C polymorphisms on disease-free and overall survival rates. Disease-free and overall survival rates were the primary endpoints of the study.

Results

The ACE (I/D) polymorphism was associated with 3-year disease-free survival. Disease-free survival in DD carriers was significantly increased compared to ID plus II carriers (HR = 4.75; 95% CI, 1.39–16.24; p = 0.013). No significant association was found between AGTR1 (A1166C) and 3-year disease-free survival (p = 0.233). Also, the ACE (I/D) and AGTR1 (A1166C) polymorphisms were not associated with breast cancer overall survival.

Conclusion

The ACE (I/D) polymorphism was associated with 3-year disease-free survival of the women with breast cancer. Besides, disease-free survival in DD carriers was significantly increased compared to ID plus II carriers.     

Coronary Heart Disease and Cortical Thickness,Gray Matter and White Matter Lesion Volumes on MRI

Coronary heart disease (CHD) has been linked with cognitive decline and dementia in several studies. CHD is strongly associated with blood pressure, but it is not clear how blood pressure levels or changes in blood pressure over time affect the relation between CHD and dementia-related pathology. The aim of this study was to investigate relations between CHD and cortical thickness, gray matter volume and white matter lesion (WML) volume on MRI, considering CHD duration and blood pressure levels from midlife to three decades later. The study population included 69 elderly at risk of dementia who participated in the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study. CAIDE participants were examined in midlife, re-examined 21 years later, and then after additionally 7 years (in total up to 30 years follow-up). MRIs from the second re-examination were used to calculate cortical thickness, gray matter and WML volume. CHD diagnoses were obtained from the Finnish Hospital Discharge Register. Linear regression analyses were adjusted for age, sex, follow-up time and scanner type, and additionally total intracranial volume in GM volume analyses. Adding diabetes, cholesterol or smoking to the models did not influence the results. CHD was associated with lower thickness in multiple regions, and lower total gray matter volume, particularly in people with longer disease duration (>10 years). Associations between CHD, cortical thickness and gray matter volume were strongest in people with CHD and hypertension in midlife, and those with CHD and declining blood pressure after midlife. No association was found between CHD and WML volumes. Based on these results, long-term CHD seems to have detrimental effects on brain gray matter tissue, and these effects are influenced by blood pressure levels and their changes over time.     

PCO(2) in the large intestine of mice, rats, guinea pigs, and dogs and effects of the dietary substrate.

PCO(2) in the lumen and serosa of cecum and colon was measured in rats, guinea pigs, and dogs to examine the relationship between serosal PCO(2) and the incidence of intestinal necrotic lesions after administration of gas-carrier contrast agents in rodents. The effects of the dietary substrate were tested in a group of mice maintained on a diet based on glucose as the only carbohydrate source. The anesthetic used was a fentanyl-fluanison-midazolam mixture (rodents) and pentobarbital (dogs). PCO(2) was measured in vivo and postmortem, and the kinetics of the postmortem serosal PCO(2) [transmural CO(2) flux (J(CO(2)))] was calculated. PCO(2) in the cecal serosa and lumen, respectively, was 64 +/- 4 and 392 +/- 18 Torr in rats, 67 +/- 3 and 276 +/- 17 Torr in guinea pigs, and 73 +/- 6 and 137 +/- 7 Torr in mice on glucose-based diet. In the colon serosa and lumen of dogs, PCO(2) was 30 +/- 6 and 523 +/- 67 Torr, respectively. Serosal PCO(2) increased rapidly after death in rats and slower in guinea pigs and mice, and the slowest change was observed in dogs. Compared with dogs, serosal PCO(2) and J(CO(2)) of rats and guinea pigs were significantly higher. Serosal PCO(2) of guinea pigs was similar to that of rats, whereas the J(CO(2)) of guinea pigs was significantly lower. These data suggest a causal relationship between the ability of the cecal and colonic wall to act as a barrier to CO(2) diffusion and the presence of characteristic gas-carrier contrast agent-induced intestinal lesions in mice and rats and their absence in guinea pigs, dogs, and other species.     

Identification of potential predictive markers of dexamethasone resistance in childhood acute lymphoblastic leukemia

Response to dexamethasone (DEXA), as a hallmark drug in the treatment of childhood acute lymphoblastic leukemia (ALL), is one of the pivotal prognostic factors in the prediction of outcome in ALL. Identification of predictive markers of chemoresistance is beneficial to selecting of the best therapeutic protocol with the lowest effect adverse. Hence, we aimed to find drug targets using the 2DE/MS proteomics study of a DEXA-resistant cell line (REH) as a model for poor DEXA responding patients before and after drug treatment. Using the proteomic methods, three differentially expressed proteins were detected, including voltage dependent anion channel 1 (VDAC1), sorting Nexin 3 (SNX3), and prefoldin subunit 6 (PFDN6). We observed low expression of three proteins after DEXA treatment in REH cells. We subsequently verified low expression of resulted proteins at the mRNA level using the quantitative PCR method. These proteins are promising proteins because of their important roles in drug resistance and regulation of apoptosis (VDAC1), protein trafficking (SNX3), and protein folding (PFDN6). Additionally, mRNA expression level of these proteins was assessed in 17 bone marrow samples from children with newly diagnosed ALL and 7 non-cancerous samples as controls. The results indicated that independent of the molecular subtypes of leukemia, mRNA expression of VDAC1, SNX3, and PFDN6 decreased in ALL samples compared with non-cancerous samples particularly in VDAC1 (p?<?0.001). Additionally, mRNA expression of three proteins was also declined in high-risk samples compared with standard risk cases. These results demonstrated diagnostic and prognostic value of these proteins in childhood ALL. Furthermore, investigation of protein-protein interaction using STRING database indicated that these proteins involved in the signaling pathway of NR3C1 as dexamethasone target. In conclusion, our proteomic study in DEXA resistant leukemic cells revealed VDAC1, SNX3, and PFDN6 are promising proteins that might serve as potential biomarkers of prognosis and chemotherapy in childhood ALL.     

Multiple introductions and invasion pathways for the invasive ctenophore Mnemiopsis leidyi in Eurasia

The introduction and spread of non-indigenous species (NIS) in marine ecosystems accelerated during the twentieth century owing to human activities, notably international shipping. Genetic analysis has proven useful in understanding the invasion history and dynamics of colonizing NIS and identifying their source population(s). Here we investigated sequence variation in the nuclear ribosomal Internal Transcribed Spacer region of the ctenophore Mnemiopsis leidyi, a species considered one of the most invasive globally. We surveyed four populations from the native distribution range along the Atlantic coasts of the United States and South America, as well as six populations in the introduced range from the Black, Azov, Caspian and Baltic seas. Allelic and nucleotide diversity of introduced populations were comparable to those of native populations from which they were likely drawn. Introduced populations typically exhibited lower genetic differentiation (F _ST = ?0.014?C0.421) than native populations (F _ST = 0.324?C0.688). Population genetic analyses supported the invasion of Eurasia from at least two different pathways, the first from the Gulf of Mexico (e.g., Tampa Bay) to the Black Sea and thence to the Caspian Sea, the second from the northern part of the native distribution range (e.g., Narragansett Bay) to the Baltic Sea. The relatively high genetic diversity observed in introduced populations is consistent with large inocula and/or multiple invasions, both of which are possible given ballast water transport and the extensive native distribution of the ctenophore in the Atlantic Ocean.