Overlapping neuronal circuits in addiction and obesity: evidence of systems pathology

Drugs and food exert their reinforcing effects in part by increasing dopamine (DA) in limbic regions, which has generated interest in understanding how drug abuse/addiction relates to obesity. Here, we integrate findings from positron emission tomography imaging studies on DA's role in drug abuse/addiction and in obesity and propose a common model for these two conditions. Both in abuse/addiction and in obesity, there is an enhanced value of one type of reinforcer (drugs and food, respectively) at the expense of other reinforcers, which is a consequence of conditioned learning and resetting of reward thresholds secondary to repeated stimulation by drugs (abuse/addiction) and by large quantities of palatable food (obesity) in vulnerable individuals (i.e. genetic factors). In this model, during exposure to the reinforcer or to conditioned cues, the expected reward (processed by memory circuits) overactivates the reward and motivation circuits while inhibiting the cognitive control circuit, resulting in an inability to inhibit the drive to consume the drug or food despite attempts to do so. These neuronal circuits, which are modulated by DA, interact with one another so that disruption in one circuit can be buffered by another, which highlights the need of multiprong approaches in the treatment of addiction and obesity.     

Store-operated calcium entry in physiology and pathology of mammalian cells

One of the numerous calcium-involving processes in mammalian cells is store-operated calcium entry (SOCE) -- the process in which depletion of calcium stores in the endoplasmic reticulum (ER) induces calcium influx from the extracellular space. Previously supposed to function only in non-excitable cells, SOCE is now known to play a role also in such excitable cells as neurons, muscles and neuroendocrine cells and is found in many different cell types. SOCE participates not only in processes dependent on ER calcium level but also specifically regulates some important processes such as cAMP production, T lymphocyte activation or induction of long-term potentiation. Impairment of SOCE can be an element of numerous disorders such as acute pancreatitis, primary immunodeficiency and, since it can take part in apoptosis or cell cycle regulation, SOCE may also be partially responsible for such serious disorders as Alzheimer disease and many types of cancer. Even disturbances in the 'servant' role of maintaining ER calcium level may cause serious effects because they can lead to ER homeostasis disturbance, influencing gene expression, protein synthesis and processing, and the cell cycle.     

Meniscal pathology - the evidence for treatment

Whilst arthroscopic surgery for the treatment of meniscal tears is the most commonly performed orthopaedic surgery, meniscal tears at the knee are frequently identified on magnetic resonance imaging in adults with and without knee pain. The evidence for arthroscopic treatment of meniscal tears is controversial and lacks a supporting evidence base; it may be no more efficacious than conservative therapies. Surgical approaches to the treatment of meniscal pathology can be broadly categorised into those in which partial menisectomy or repair are performed. This review highlights that the major factor determining the choice of operative approach is age: meniscal repair is performed exclusively on younger populations, while older populations are subject to partial menisectomy procedures. This is probably because the meniscus is less amenable to repair in the older population where other degenerative changes co-exist. In middle-aged to older adults, arthroscopic partial menisectomy (APM) may treat the meniscus tear, but does not address the degenerative whole organ disease of knee osteoarthritis. Thus far, there is no convincing evidence that operative approaches are superior to conservative measures as the first-line treatment of older people with knee pain and meniscal tears. However, in two randomised controlled trials (RCTs) approximately one-third of subjects in the exercise groups had persisting knee pain with some evidence of improvement following APM, although the characteristics of this subgroup are unclear. From the available data, a first-line trial of conservative therapy, which includes weight loss, is recommended for the treatment of degenerative meniscal tears in older adults. The exception to this may be when mechanical symptoms, such as knee locking, predominate. Although requiring corroboration by RCTs, there is accumulating evidence from cohort studies and case series that meniscal repair rather than APM may improve function and reduce the long-term risk of knee osteoarthritis in young adults. There is no clear evidence from RCTs that one surgical method of meniscal repair is superior to another.     

Raman spectroscopy and order in biological systems

The Raman spectra in the low 5–200 cm⁻¹ frequency region of metabolically activeE. coli cells have been analyzed to determine whether they are indicators of a possible in vivo underlying order by applying standard concepts derived from the Raman spectroscopy of crystalline systems with varying degrees of order. The analysis suggests that in-vivo space-time ordered structures involving amino acids associated with DNA exist since the low frequency lines of metabolically active cells can be assigned to lines seen in the spectra of crystals of given amino acids known to associated with DNA early in the lifetime of a cell.     

Raman spectroscopy and order in biological systems

The Raman spectra in the low 5-200 cm-1 frequency region of metabolically active E. coli cells have been analyzed to determine whether they are indicators of a possible in vivo underlying order by applying standard concepts derived from the Raman spectroscopy of crystalline systems with varying degrees of order. The analysis suggests that in-vivo space-time ordered structures involving amino acids associated with DNA exist since the low frequency lines of metabolically active cells can be assigned to lines seen in the spectra of crystals of given amino acids known to associate with DNA early in the lifetime of a cell.     

Relationship between order of entry in slaughterhouse raceway and time to traverse raceway

Problems with agitated cattle have been observed in slaughter houses. This study was conducted to determine if at the beginning of the slaughter process fewer handling problems were present. Time spent to cover a distance of 20 m in a single file race to the stunner was measured in 180 cattle. A positive relation was found (r=0.99) between the order of entry and time taken to traverse the single file runway within the groups of steers. Animals at the beginning of each group of five to seven cattle traversed the runway more quickly.     

Optimizing the evidence for linkage by permuting marker order

We developed a new marker-reordering algorithm to find the best order of fine-mapping markers for multipoint linkage analysis. The algorithm searches for the best order of fine-mapping markers such that the sum of the squared differences in identity-by-descent distribution between neighboring markers is minimized. To test this algorithm, we examined its effect on the evidence for linkage in the simulated and the Collaborative Studies on Genetics of Alcoholism (COGA) data. We found enhanced evidence for linkage with the reordered map at the true location in the simulated data (p-value decreased from 1.16 x 10(-9) to 9.70 x 10(-10)). Analysis of the White population from the COGA data with the reordered map for alcohol dependence led to a significant change of the linkage signal (p = 0.0365 decreased to p = 0.0039) on chromosome 1 between marker D1S1592 and D1S1598. Our results suggest that reordering fine-mapping markers in candidate regions when the genetic map is uncertain can be a critical step when considering a dense map.     

Dysregulation pathology of hemopoietic and immune systems under infectious process

Blood system and immune system play the crucial role in maintenance of anti-infectious defence of macroorganism. Meanwhile, infectious agents, differencing by their nature, have marked mutafacient effect on immunocompetent cells of blood. Dysregulation of DNK-reparation systems, apoptosis and immunity, maintaining genetic homeostasis of organism, is considered to be the basic reason of cytogenetic instability under infectious process. It has been established, that disturbances in blood and immunity systems, following infectious process, are caused by not only direct or indirect action of infectious agents on mature immunocytes, but else by their stimulating or suppressed influence on functional properties of early cells-precursors of hemo- and immunopoesis and hemopoietic microenvironment.     

Theligonaceae: Pigment and ultrastructural evidence which excludes it from the order centrospermae

The discovery of anthocyanins (and no betalains) along with S-type sieve-element plastids in Theligonum cynocrambe supports the exclusion of this taxon from the order Centrospermae.     

Worldwide phylogeography of limpets of the order Patellogastropoda: molecular, morphological and palaeontological evidence

A molecular phylogeny, based on sequence data from three mitochondrial(12S rRNA, 16S rRNA and COI) genes, is presented for the Patellogastropoda,including representatives of almost all genera belonging tothe Acmaeidae, Lepetidae, Lottiidae, Nacellidae and Patellidae.For comparison, a smaller dataset of sequences from two nuclear(18S rRNA and 28S rRNA) genes is presented. The mitochondrialgene phylogeny shows considerable disagreement with earlierhypotheses derived from morphological data. The Patellidae,Nacellidae and Lepetidae are monophyletic, but the Acmaeidaeand Lottiidae are polyphyletic. The family Acmaeidae is dividedinto two clades corresponding to the subfamilies Acmaeinae andPectinodontinae, but these two do not form a clade. The Acmaeinaeare synonymized with the Lottiidae, and the Pectinodontinaeare elevated to familial rank. Our results suggest that thePatelloida profunda group (formerly assigned to the Lottiidae)is the most basal group within the Patellogastropoda. We assignthis group to a new genus, Eoacmaea, in the new family Eoacmaeidae.We used a Bayesian Markov-Chain Monte Carlo approach togetherwith the fossil record to estimate divergence times from thecombined DNA sequence data. The lineage of extant Patellogastropodais estimated to have originated as long ago as Late Jurassic.The phylogeny also suggests that the principal clades and antitropicaldistribution pattern of the Patellogastropoda formed duringthe Mesozoic to early Cenozoic, in association with the disruptionof Pangea and following the establishment and decline of thecircumglobal equatorial current. (Received 6 November 2006; accepted 19 December 2006)     

Genetic evidence supporting caveolae microdomain regulation of calcium entry in endothelial cells

Various cellular signals initiate calcium entry into cells, and there is evidence that lipid rafts and caveolae may concentrate proteins that regulate transmembrane calcium fluxes. Here, using mice deficient in caveolin-1 (Cav-1) and Cav-1 knock-out reconstituted with endothelium-specific Cav-1, we show that Cav-1 is essential for calcium entry in endothelial cells and governs the localization and protein-protein interactions between transient receptor channels C4 and C1. Thus, Cav-1 is required for calcium entry in vascular endothelial cells and perhaps other specialized cell types containing caveolae.