Noisy neural nets exhibiting memory domains

Previous studies with probabilistic neural nets in which the neural connections are set up by means of chemical markers, revealed the existence of multiple memory domains. We generalized these studies by considering the intrinsic noise of the systems, caused by the spontaneous release of synaptic transmitter substance. A simple mathematical model is developed, which yields characteristics of multiple memory domains analogous to those occurring in noiseless nets.     

Mycorrhizal suppression and phosphorus addition influence the stability of plant community composition and function in a temperate steppe

Nutrient enrichment can reduce ecosystem stability, typically measured as temporal stability of a single function, e.g. plant productivity. Moreover, nutrient enrichment can alter plant–soil interactions (e.g. mycorrhizal symbiosis) that determine plant community composition and productivity. Thus, it is likely that nutrient enrichment and interactions between plants and their soil communities co-determine the stability in plant community composition and productivity. Yet our understanding as to how nutrient enrichment affects multiple facets of ecosystem stability, such as functional and compositional stability, and the role of above–belowground interactions are still lacking. We tested how mycorrhizal suppression and phosphorus (P) addition influenced multiple facets of ecosystem stability in a three-year field study in a temperate steppe. Here we focused on the functional and compositional stability of plant community; functional stability is the temporal community variance in primary productivity; compositional stability is represented by compositional resistance, turnover, species extinction and invasion. Community variance was partitioned into population variance defined as community productivity weighted average of the species temporal variance in performance, and species synchrony defined as the degree of temporal positive covariation among species. Compared to treatments with mycorrhizal suppression, the intact AM fungal communities reduced community variance in primary productivity by reducing species synchrony at high levels of P addition. Species synchrony and population variance were linearly associated with community variance with the intact AM fungal communities, while these relationships were decoupled or weakened by mycorrhizal suppression. The intact AM fungal communities promoted the compositional resistance of plant communities by reducing compositional turnover, but this effect was suppressed by P addition. P addition increased the number of species extinctions and thus promoted compositional turnover. Our study shows P addition and AM fungal communities can jointly and independently modify the various components of ecosystem stability in terms of plant community productivity and composition.     

Interplay between apoptotic and autophagy pathways after exposure to cerium dioxide nanoparticles in human monocytes

Engineered nanomaterials, defined as having at least one dimension smaller than 100 nm, have revolutionized many technology sectors ranging from therapeutics and diagnostics to environmental monitoring and remediation. This has resulted in a rapid increase in their manufacture over the past few years, accompanied by an increased human exposure potential. However, understanding of the interactions of nanomaterials with biological systems is still rudimentary. We have described that an environmentally and medically relevant nano metal (cerium dioxide) can affect primary human monocyte viability and interact with programmed cell death pathways leading to apoptosis and autophagic cell death. Cerium dioxide nanoparticles (CeO₂ NPs)-induced autophagy acts as a prodeath mechanism and leads to increased cytotoxicity of human monocytes. A better understanding of the implication and biological significance of CeO₂ NPs-induced autophagy and apoptosis will help us understand the risks associated with its uses and develop safer nanomedicine.     

Radiochemical and radiobiological assessment of a pyridyl-S-cysteine functionalized bombesin derivative labeled with the 99mTc(CO)3+ core

Bombesin is a neuropeptide widely studied due to its ability to target various types of cancers. Technetium-99m on the other hand is ideal for diagnostic tumor targeting. The aim of the present study is the investigation of the coupling of the ligand (S)-(2-(2′-pyridyl)ethyl)-d,l-cysteine with the BN-peptide Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met(CONH₂) through the spacer aminohexanoic acidand the labeling of the resulting derivative MBN with the synthon [M(CO)₃(H₂O)₃]⁺ (M = ^99mTc, Re). The peptide was synthesized according to the SPPS method, purified and characterized by ESI-MS. The new ^99mTc-labeled biomolecule was stable in vitro, showed high affinity for the human GRP receptor expressed in PC3 cells and the rate of internalization was found to be time-dependent tissue distribution of the radiopeptide was evaluated in normal mice and in prostate cancer experimental models and significant radioactivity uptake was observed in the pancreas of normal mice as well as in PC3 tumors. Dynamic studies of the radiopeptide showed satisfactory tumor images.     

Quinidine: an “Endangered Species” Drug Appropriate for Management of Electrical Storm in Brugada Syndrome

Brugada syndrome is an inherited channelopathy associated with an increased risk of syncope and sudden cardiac death. In rare cases it can be manifested with electrical storm. We report two cases of Brugada syndrome that presented with electrical storm and were treated successfully with oral quinidine, an "endangered species" drug.     

Effect of Acute Negative and Positive Energy Balance on Basal Very-Low Density Lipoprotein Triglyceride Metabolism in Women

Background

Acute reduction in dietary energy intake reduces very low-density lipoprotein triglyceride (VLDL-TG) concentration. Although chronic dietary energy surplus and obesity are associated with hypertriglyceridemia, the effect of acute overfeeding on VLDL-TG metabolism is not known.

Objective

The aim of the present study was to investigate the effects of acute negative and positive energy balance on VLDL-TG metabolism in healthy women.

Design

Ten healthy women (age: 22.0±2.9 years, BMI: 21.2±1.3 kg/m²) underwent a stable isotopically labeled tracer infusion study to determine basal VLDL-TG kinetics after performing, in random order, three experimental trials on the previous day: i) isocaloric feeding (control) ii) hypocaloric feeding with a dietary energy restriction of 2.89±0.42 MJ and iii) hypercaloric feeding with a dietary energy surplus of 2.91±0.32 MJ. The three diets had the same macronutrient composition.

Results

Fasting plasma VLDL-TG concentrations decreased by ∼26% after hypocaloric feeding relative to the control trial (P = 0.037), owing to decreased hepatic VLDL-TG secretion rate (by 21%, P = 0.023) and increased VLDL-TG plasma clearance rate (by ∼12%, P = 0.016). Hypercaloric feeding increased plasma glucose concentration (P = 0.042) but had no effect on VLDL-TG concentration and kinetics compared to the control trial.

Conclusion

Acute dietary energy deficit (∼3MJ) leads to hypotriglyceridemia via a combination of decreased hepatic VLDL-TG secretion and increased VLDL-TG clearance. On the other hand, acute dietary energy surplus (∼3MJ) does not affect basal VLDL-TG metabolism but disrupts glucose homeostasis in healthy women.     

Inter‐α‐inhibitor deficiency in the mouse is associated with alterations in anxiety‐like behavior,exploration and social approach

In recent years, several genome‐wide association studies have identified candidate regions for genetic susceptibility in major mood disorders. Most notable are regions in a locus in chromosome 3p21, encompassing the genes NEK4‐ITIH1‐ITIH3‐ITIH4. Three of these genes represent heavy chains of the composite protein inter‐α‐inhibitor (IαI). In order to further establish associations of these genes with mood disorders, we evaluated behavioral phenotypes in mice deficient in either Ambp/bikunin, which is necessary for functional ITIH1 and ITIH3 complexes, or in Itih4, the gene encoding the heavy chain Itih4. We found that loss of Itih4 had no effect on the behaviors tested, but loss of Ambp/bikunin led to increased anxiety‐like behavior in the light/dark and open field tests and reduced exploratory activity in the elevated plus maze, light/dark preference and open field tests. Ambp/bikunin knockout mice also exhibited a sex‐dependent exaggeration of acoustic startle responses, alterations in social approach during a three‐chamber choice test, and an elevated fear conditioning response. These results provide experimental support for the role of ITIH1/ITIH3 in the development of mood disorders.     

Intravascular heavy chain-modification of hyaluronan during endotoxic shock

During inflammation, the covalent linking of the ubiquitous extracellular polysaccharide hyaluronan (HA) with the heavy chains (HC) of the serum protein inter alpha inhibitor (IαI) is exclusively mediated by the enzyme tumor necrosis factor α (TNFα)-stimulated-gene-6 (TSG-6). While significant advances have been made regarding how HC-modified HA (HC-HA) is an important regulator of inflammation, it remains unclear why HC-HA plays a critical role in promoting survival in intraperitoneal lipopolysaccharide (LPS)-induced endotoxemia while exerting only a modest role in the outcomes following intratracheal exposure to LPS. To address this gap, the two models of intraperitoneal LPS-induced endotoxic shock and intratracheal LPS-induced acute lung injury were directly compared in TSG-6 knockout mice and littermate controls. HC-HA formation, endogenous TSG-6 activity, and inflammatory markers were assessed in plasma and lung tissue. TSG-6 knockout mice exhibited accelerated mortality during endotoxic shock. While both intraperitoneal and intratracheal LPS induced HC-HA formation in lung parenchyma, only systemically-induced endotoxemia increased plasma TSG-6 levels and intravascular HC-HA formation. Cultured human lung microvascular endothelial cells secreted TSG-6 in response to both TNFα and IL1β stimulation, indicating that, in addition to inflammatory cells, the endothelium may secrete TSG-6 into circulation during systemic inflammation. These data show for the first time that LPS-induced systemic inflammation is uniquely characterized by significant vascular induction of TSG-6 and HC-HA, which may contribute to improved outcomes of endotoxemia.     

Genetic variation among Mediterranean populations of Sesamia nonagrioides (Lepidoptera: Noctuidae) as revealed by RFLP mtDNA analysis

Restriction fragment length polymorphism analysis of two segments of mitochondrial DNA (COI and 16S rRNA) was used to examine genetic variation in Sesamia nonagrioides (Lefèbvre) populations from the Mediterranean basin. Four populations were collected from central and southern Greece, and five from northern latitudes: Greece, Italy, France and Spain. No variation was observed in COI, while 16S rRNA segment proved highly polymorphic and 28 different haplotypes were found. Lower intra-population polymorphism was found in the northern populations than in southern ones. Although no significant isolation by distance was found, the UPGMA tree based on Nei's raw number of nucleotide differences separated the populations into two major groups, i.e. one with the northern (40.6 degrees N-43.4 degrees N) and the other with the southern populations (37.3 degrees N-39.2 degrees N). Analysis of molecular variance revealed that most of the variation was between the two major groups (Phi(CT)=0.559), and all pairwise comparisons between the northern and southern populations resulted in high and significant F(ST) values (overall F(ST)=0.604). The high F(ST) values and the strong spatial genetic structure indicate that long-distance migration may be a rare event. The populations do not seem to have experienced a strong historical bottleneck. The occurrence of a few widespread haplotypes and the genetic similarity of the northern populations could be attributed to a historical expansion of certain haplotypes from the south towards to the northern borders of the species' distribution area.