Early alterations in hippocampal circuitry and theta rhythm generation in a mouse model of prenatal infection: implications for schizophrenia

Post-mortem studies suggest that GABAergic neurotransmission is impaired in schizophrenia. However, it remains unclear if these changes occur early during development and how they impact overall network activity. To investigate this, we used a mouse model of prenatal infection with the viral mimic, polyriboinosinic-polyribocytidilic acid (poly I:C), a model based on epidemiological evidence that an immune challenge during pregnancy increases the prevalence of schizophrenia in the offspring. We found that prenatal infection reduced the density of parvalbumin- but not somatostatin-positive interneurons in the CA1 area of the hippocampus and strongly reduced the strength of inhibition early during postnatal development. Furthermore, using an intact hippocampal preparation in vitro, we found reduced theta oscillation generated in the CA1 area. Taken together, these results suggest that redistribution in excitatory and inhibitory transmission locally in the CA1 is associated with a significant alteration in network function. Furthermore, given the role of theta rhythm in memory, our results demonstrate how a risk factor for schizophrenia can affect network function early in development that could contribute to cognitive deficits observed later in the disease.     

Expert opinion on laparoscopic surgery for colorectal cancer parallels evidence from a cumulative meta-analysis of randomized controlled trials

Background

This study sought to synthesize survival outcomes from trials of laparoscopic and open colorectal cancer surgery, and to determine whether expert acceptance of this technology in the literature has parallel cumulative survival evidence.

Study Design

A systematic review of randomized trials was conducted. The primary outcome was survival, and meta-analysis of time-to-event data was conducted. Expert opinion in the literature (published reviews, guidelines, and textbook chapters) on the acceptability of laparoscopic colorectal cancer was graded using a 7-point scale. Pooled survival data were correlated in time with accumulating expert opinion scores.

Results

A total of 5,800 citations were screened. Of these, 39 publications pertaining to 23 individual trials were retained. As well, 414 reviews were included (28 guidelines, 30 textbook chapters, 20 systematic reviews, 336 narrative reviews). In total, 5,782 patients were randomized to laparoscopic (n = 3,031) and open (n = 2,751) colorectal surgery. Survival data were presented in 16 publications. Laparoscopic surgery was not inferior to open surgery in terms of overall survival (HR = 0.94, 95% CI 0.80, 1.09). Expert opinion in the literature pertaining to the oncologic acceptability of laparoscopic surgery for colon cancer correlated most closely with the publication of large RCTs in 2002–2004. Although increasingly accepted since 2006, laparoscopic surgery for rectal cancer remained controversial.

Conclusions

Laparoscopic surgery for colon cancer is non-inferior to open surgery in terms of overall survival, and has been so since 2004. The majority expert opinion in the literature has considered these two techniques to be equivalent since 2002–2004. Laparoscopic surgery for rectal cancer has been increasingly accepted since 2006, but remains controversial. Knowledge translation efforts in this field appear to have paralleled the accumulation of clinical trial evidence.     

The iodocyanopindolol and SM-11044 binding protein belongs to the TM9SF multispanning membrane protein superfamily

SM-11044 is the only beta-adrenergic agonist that inhibits guinea pig eosinophil chemotaxis and induces relaxation of depolarized rat colon tonus. We have previously reported the purification of a 34 kDa photoaffinity-labeled SM-11044 binding protein (SMBP) from rat colon that may mediate the biological effects of the ligand and that differs from all known monoamine receptors (Sugasawa et al., J. Biol. Chem. 272 (1997) 21244). The present report describes partial amino acid sequence of rat SMBP and molecular cloning of corresponding human SMBP (hSMBP) cDNA. This cDNA encodes a 588 amino acid residue polypeptide comprising a signal peptide, a long hydrophilic amino-terminal region, and a highly hydrophobic C-terminal portion organized into nine putative transmembrane domains. The sequence and structure of hSMBP shows homology to members of a new transmembrane protein 9 superfamily (TM9SF). Comparison of hSMBP with related protein sequences from yeast, plant and human revealed two subgroups within TM9SF. The members of these groups differ in length and have characteristic amino acid sequence motifs in their amino-terminal portion. Northern blot analysis revealed two major SMBP mRNAs, at 3.4 and 3.8 kb, that were present in all the human tissues examined. Western blot experiments detected SMBP as a 70 kDa protein that may be further cleaved into an active 34 kDa N-terminal polypeptide. Stable Chinese Hamster Ovary cell transfectants expressing hSMBP cDNA displayed specific binding of [(125)I]iodocyanopindolol that was displaced by SM-11044 in a dose-dependent manner. Thus, SMBP is the first member of TM9SF with functional ligand binding properties, suggesting that some of these integral membrane proteins may function as channels, small molecule transporters or receptors.     

Why are literature data for H2O2 contents so variable? A discussion of potential difficulties in the quantitative assay of leaf extracts

Leaf metabolism produces H₂O₂ at high rates, but current conceptssuggest that the potent signalling effects of this oxidant requirethat concentrations be controlled by a battery of antioxidativeenzymes. The extent to which H₂O₂ is allowed to accumulate remainsunclear. There is little consensus on leaf H₂O₂ values in theliterature and measured concentrations in unstressed conditionsrange from 50–5000 nmol g^–1 fresh weight, a differencethat probably reflects technical inaccuracies as much as biologicalvariability. This article uses new experimental and literaturedata to examine some of the difficulties in accurately measuringH₂O₂ in leaf extracts. Potential problems relate to sensitivity,interference from other redox-active compounds, and H₂O₂ stabilityduring sample preparation. Particular attention is drawn tothe influence of tissue mass/extraction volume in the quantitativeestimation of H₂O₂ contents, and the possibility that this factorcould contribute to the variability of literature data. Key words: Ascorbate, chemiluminescence, oxidative stress, redox signalling, xylenol orange Received 4 June 2007; Revised 18 June 2007 Accepted 23 June 2007     

Viability of brown trout embryos positively linked to melanin-based but negatively to carotenoid-based colours of their fathers

'Good-genes' models of sexual selection predict significant additive genetic variation for fitness-correlated traits within populations to be revealed by phenotypic traits. To test this prediction, we sampled brown trout (Salmo trutta) from their natural spawning place, analysed their carotenoid-based red and melanin-based dark skin colours and tested whether these colours can be used to predict offspring viability. We produced half-sib families by in vitro fertilization, reared the resulting embryos under standardized conditions, released the hatchlings into a streamlet and identified the surviving juveniles 20 months later with microsatellite markers. Embryo viability was revealed by the sires' dark pigmentation: darker males sired more viable offspring. However, the sires' red coloration correlated negatively with embryo survival. Our study demonstrates that genetic variation for fitness-correlated traits is revealed by male colour traits in our study population, but contrary to predictions from other studies, intense red colours do not signal good genes.     

Three-dimensional quantitative structure-activity relationship (CoMFA and CoMSIA) studies on galardin derivatives as gelatinase A (matrix metalloproteinase 2) inhibitors

Three-dimensional quantitative structure-activity relationship models have been derived using comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA) and molecule docking for the training sets of galardin-based matrix metalloproteinase inhibitors (MMPIs). The statistical values for the best models are significant. The models showed that the steric effect near the S1' pocket and hydrogen-bonding effect of the zinc binding group play key roles on the inhibitory activity of gelatinase A. The sets of the training and test proved the models were stable and predictive, and may have a good prediction for the inhibition activities of galardin derivatives as gelatinase A inhibitors. The results not only lead to a better understanding of the molecular mechanisms and structural requirements of gelatinase A inhibitors but also can help to design novel inhibitors against gelatinase A.     

quantiNemo: an individual-based program to simulate quantitative traits with explicit genetic architecture in a dynamic metapopulation

quantiNemo is an individual-based, genetically explicit stochastic simulation program. It was developed to investigate the effects of selection, mutation, recombination and drift on quantitative traits with varying architectures in structured populations connected by migration and located in a heterogeneous habitat. quantiNemo is highly flexible at various levels: population, selection, trait(s) architecture, genetic map for QTL and/or markers, environment, demography, mating system, etc. quantiNemo is coded in C++ using an object-oriented approach and runs on any computer platform. Availability: Executables for several platforms, user's manual, and source code are freely available under the GNU General Public License at http://www2.unil.ch/popgen/softwares/quantinemo.     

Influence of shoes increasing dorsiflexion and decreasing metatarsus flexion on lower limb muscular activity during fitness exercises, walking, and running

The aim of the present study was to compare electromyographic activity during fitness exercises, walking, and running among 3 different dorsiflexion shoes (+2 degrees , +4 degrees , and +10 degrees ) and standard shoes (-4 degrees ). The 3 different dorsiflexion shoes tested in this study have a curvature placed in the middle of the sole. This design was specially projected to decrease the metatarsus flexion. Electromyographic activity of 9 lower limb muscles was measured on 12 healthy female subjects during 5 fitness exercises (unload squat, side and front step, submaximal ballistic plantar flexion, and lunge exercise), and during running (10 km x h(-1)) and walking (4.5 km x h(-1)) on a treadmill. EMG signal was analyzed with the root mean square (RMS) and integrated EMG. All RMS data measured during these exercises were expressed as percentages of maximum voluntary isometric contraction. The results show that dorsiflexion affects muscle recruitment and reorganizes the motor pattern. The general tendency was that the tibialis anterior activity increased with dorsiflexion. However, an optimal dorsiflexion existed for various exercises. It is concluded that shoes with moderate dorsiflexion can activate lower limb muscles differently compared with both standard shoes and shoes with large dorsiflexion during submaximal exercises and locomotion.