Natural antisense transcripts with coding capacity in Arabidopsis may have a regulatory role that is not linked to double-stranded RNA degradation

BACKGROUND: Overlapping transcripts in antisense orientation have the potential to form double-stranded RNA (dsRNA), a substrate for a number of different RNA-modification pathways. One prominent route for dsRNA is its breakdown by Dicer enzyme complexes into small RNAs, a pathway that is widely exploited by RNA interference technology to inactivate defined genes in transgenic lines. The significance of this pathway for endogenous gene regulation remains unclear. RESULTS: We have examined transcription data for overlapping gene pairs in Arabidopsis thaliana. On the basis of an analysis of transcripts with coding regions, we find the majority of overlapping gene pairs to be convergently overlapping pairs (COPs), with the potential for dsRNA formation. In all tissues, COP transcripts are present at a higher frequency compared to the overall gene pool. The probability that both the sense and antisense copy of a COP are co-transcribed matches the theoretical value for coexpression under the assumption that the expression of one partner does not affect the expression of the other. Among COPs, we observe an over-representation of spliced (intron-containing) genes (90%) and of genes with alternatively spliced transcripts. For loci where antisense transcripts overlap with sense transcript introns, we also find a significant bias in favor of alternative splicing and variation of polyadenylation. CONCLUSION: The results argue against a predominant RNA degradation effect induced by dsRNA formation. Instead, our data support alternative roles for dsRNAs. They suggest that at least for a subgroup of COPs, antisense expression may induce alternative splicing or polyadenylation

Evolution of antimicrobial prophylaxis in cardiovascular surgery

Objective: To examine the optimal duration of antibiotic prophylaxis in major cardiovascular surgery. Methods: In the past 15 years, four prospective randomized, controlled studies, conducted by the same group of authors, compared seven prophylactic antimicrobial regimens in 2970 patients undergoing major cardiovascular surgery. In 1980/81, a 4-day cefazolin (CFZ) prophylaxis was compared with a 2-day cefuroxime (CFX) administration (n=566). In 1982/83, a 2-day CFX prophylaxis was compared with a two shot ceftriaxone (CRO) prophylaxis (n=512). In 1984/87, a 1-day CFZ prophylaxis was compared with a single shot prophylaxis of CRO (n=883). In 1994/1995, a 4 day combination of amoxicillin (AM) and netilmicin (NET) prophylaxis was compared with a single shot prophylaxis of CFX (n=1009). Results: Total infection rate varied between 4.5 and 5.7%, despite different antimicrobial regimen used and their varying duration. Wound infection rate was 1.1% (range 0.4-2.5%), sepsis rate was 0.8% (range 0.4-1.6%), pneumonia rate 2% (0.7-2.9%), urinary tract infection rate 0.4% (range 0-1.4%), and central venous catheter-related infection rate was 0.4% (0-1%). The 30-day mortality rate was 1.3% (range 0.4-2%). All these differences were not statistically significant. Conclusions: A low infection rate (range 4.5-5.7%) occurred despite changes in duration of various prophylactic antibiotic regimen with cephalosporins of first, second or third generation. As a single shot prophylaxis could nowadays successfully be used in cardiovascular surgery, no postoperative antibiotics should be used, unless an intraoperative or a postoperative infection is documented or in presence of major perioperative complication

Development of a chemically defined medium and discovery of new mitogenic growth factors for mouse hepatocytes: Mitogenic effects of FGF1/2 and PDGF

Chemically defined serum-free media for rat hepatocytes have been useful in identifying EGFR ligands and HGF/MET signaling as direct mitogenic factors for rat hepatocytes. The absence of such media for mouse hepatocytes has prevented screening for discovery of such mitogens for mouse hepatocytes. We present results obtained by designing such a chemically defined medium for mouse hepatocytes and demonstrate that in addition to EGFR ligands and HGF, the growth factors FGF1 and FGF2 are also important mitogenic factors for mouse hepatocytes. Smaller mitogenic response was also noticed for PDGF AB. Mouse hepatocytes are more likely to enter into spontaneous proliferation in primary culture due to activation of cell cycle pathways resulting from collagenase perfusion. These results demonstrate unanticipated fundamental differences in growth biology of hepatocytes between the two rodent species. Copyright: © 2014 Reekie et al

Hepatocellular carcinomas in native livers from patients treated with orthotopic liver transplantation: Biologic and therapeutic implications

The gross and histopathologic characteristics of 212 nonfibrolamellar hepatocellular carcinomas (HCCs) discovered in native livers removed at the time of liver transplantation were correlated with features of invasive growth and tumor-free survival. The results show that most HCCs begin as small well-differentiated tumors that have an increased proliferation rate and induce neovascularization, compared with the surrounding liver. But at this stage, they maintain a near-normal apoptosis/mitosis ratio and uncommonly show vascular invasion. As tumors enlarge, foci of dedifferentiation appear within the neoplastic nodules, which have a higher proliferation rate and show more pleomorphism than surrounding better-differentiated areas. Vascular invasion, which is the strongest predictor of disease recurrence, correlates significantly with tumor number and size, tumor giant cells and necrosis, the predominant and worst degree of differentiation, and the apoptosis/mitosis ratio. In the absence of macroscopic or large vessel invasion, largest tumor size (P <.006), apoptosis/mitosis ratio (P <.03), and number of tumors (P <.04) were independent predictors of tumor-free survival and none of 24 patients with tumors having an apoptosis/mitosis ratio greater than 7.2 had recurrence. A minority of HCCs (< 15%) quickly develop aggressive features (moderate or poor differentiation, low apoptosis/mitosis ratio, and vascular invasion) while still small, similar to flat carcinomas of the bladder and colon. In conclusion, hepatic carcinogenesis in humans is a multistep and multifocal process. As in experimental animal studies, aggressive biologic behavior (vascular invasion and recurrence) correlates significantly with profound alterations in the apoptosis/mitosis ratio and with architectural and cytologic alterations that suggest a progressive accumulation of multiple genetic abnormalities

Modeling and Simulation of Multi-Lane Traffic Flow

A most important aspect in the field of traffic modeling is the simulation of bottleneck situations. For their realistic description a macroscopic multi-lane model for uni-directional freeways including acceleration, deceleration, velocity fluctuations, overtaking and lane-changing maneuvers is systematically deduced from a gas-kinetic (Boltzmann-like) approach. The resulting equations contain corrections with respect to previous models. For efficient computer simulations, a reduced model delineating the coarse-grained temporal behavior is derived and applied to bottleneck situations.Comment: For related work see http://www.theo2.physik.uni-stuttgart.de/helbing.htm

An optimized TOPS+ comparison method for enhanced TOPS models

This article has been made available through the Brunel Open Access Publishing Fund.Background Although methods based on highly abstract descriptions of protein structures, such as VAST and TOPS, can perform very fast protein structure comparison, the results can lack a high degree of biological significance. Previously we have discussed the basic mechanisms of our novel method for structure comparison based on our TOPS+ model (Topological descriptions of Protein Structures Enhanced with Ligand Information). In this paper we show how these results can be significantly improved using parameter optimization, and we call the resulting optimised TOPS+ method as advanced TOPS+ comparison method i.e. advTOPS+. Results We have developed a TOPS+ string model as an improvement to the TOPS [1-3] graph model by considering loops as secondary structure elements (SSEs) in addition to helices and strands, representing ligands as first class objects, and describing interactions between SSEs, and SSEs and ligands, by incoming and outgoing arcs, annotating SSEs with the interaction direction and type. Benchmarking results of an all-against-all pairwise comparison using a large dataset of 2,620 non-redundant structures from the PDB40 dataset [4] demonstrate the biological significance, in terms of SCOP classification at the superfamily level, of our TOPS+ comparison method. Conclusions Our advanced TOPS+ comparison shows better performance on the PDB40 dataset [4] compared to our basic TOPS+ method, giving 90 percent accuracy for SCOP alpha+beta; a 6 percent increase in accuracy compared to the TOPS and basic TOPS+ methods. It also outperforms the TOPS, basic TOPS+ and SSAP comparison methods on the Chew-Kedem dataset [5], achieving 98 percent accuracy. Software Availability: The TOPS+ comparison server is available at http://balabio.dcs.gla.ac.uk/mallika/WebTOPS/.This article is available through the Brunel Open Access Publishing Fun

Conditional Genetic Elimination of Hepatocyte Growth Factor in Mice Compromises Liver Regeneration after Partial Hepatectomy

Hepatocyte growth factor (HGF) has been shown to be indispensable for liver regeneration because it serves as a main mitogenic stimulus driving hepatocytes toward proliferation. We hypothesized that ablating HGF in adult mice would have a negative effect on the ability of hepatocytes to regenerate. Deletion of the HGF gene was achieved by inducing systemic recombination in mice lacking exon 5 of HGF and carrying the Mx1-cre or Cre-ERT transgene. Analysis of liver genomic DNA from animals 10 days after treatment showed that a majority (70-80%) of alleles underwent cre-induced genetic recombination. Intriguingly, however, analysis by RT-PCR showed the continued presence of both unrecombined and recombined forms of HGF mRNA after treatment. Separation of liver cell populations into hepatocytes and non-parenchymal cells showed equal recombination of genomic HGF in both cell types. The presence of the unrecombined form of HGF mRNA persisted in the liver in significant amounts even after partial hepatectomy (PH), which correlated with insignificant changes in HGF protein and hepatocyte proliferation. The amount of HGF produced by stellate cells in culture was indirectly proportional to the concentration of HGF, suggesting that a decrease in HGF may induce de novo synthesis of HGF from cells with residual unrecombined alleles. Carbon tetrachloride (CCl4)-induced regeneration resulted in a substantial decrease in preexisting HGF mRNA and protein, and subsequent PH led to a delayed regenerative response. Thus, HGF mRNA persists in the liver even after genetic recombination affecting most cells; however, PH subsequent to CCl4 treatment is associated with a decrease in both HGF mRNA and protein and results in compromised liver regeneration, validating an important role of this mitogen in hepatic growth. © 2013 Nejak-Bowen et al

Macroscopic Dynamics of Multi-Lane Traffic

We present a macroscopic model of mixed multi-lane freeway traffic that can be easily calibrated to empirical traffic data, as is shown for Dutch highway data. The model is derived from a gas-kinetic level of description, including effects of vehicular space requirements and velocity correlations between successive vehicles. We also give a derivation of the lane-changing rates. The resulting dynamic velocity equations contain non-local and anisotropic interaction terms which allow a robust and efficient numerical simulation of multi-lane traffic. As demonstrated by various examples, this facilitates the investigation of synchronization patterns among lanes and effects of on-ramps, off-ramps, lane closures, or accidents.Comment: For related work see http://www.theo2.physik.uni-stuttgart.de/helbing.htm

Gallstone Obstructive Ileus 3 Years Post-cholecystectomy to a Patient with an Old Ileoileal Anastomosis

The present case is one of gallstone obstructive ileus due to gallstones 3 yr after laparoscopic cholecystectomy. It is interesting because of the sex of the patient, the fact that ileus occurred 3 yr after cholecystectomy and that the localization of the obstruction was an old side-to-side ileoileal anastomosis due to a diverticulectomy following intussusception of Meckels' diverticulum at the age of 3

Anterior chest wall tuberculous abscess: a case report

The granulomatous inflammation of tuberculosis usually involves the lungs and the hilar lymph nodes. Musculoskeletal tuberculosis (TB) occurs in 1–3% of patients with TB, while TB of the chest wall constitutes 1% to 5% of all cases of musculoskeletal TB. Furthermore, nowadays it is rarer to find extrapulmonary TB in immunocompetent rather that non-immunocompetent patients. The present case reports a fifty-six-year-old immunocompetent man with an anterior chest wall tuberculous abscess. The rarity of the present case relates both to the localization of the tuberculous abscess, and to the fact that the patient was immunocompetent. The diagnosis of musculoskeletal tuberculous infection remains a challenge for clinicians and requires a high index of suspicion. The combination of indolent onset of symptoms, positive tuberculin skin test, and compatible radiographic findings, strongly suggests the diagnosis. TB, however, must be confirmed by positive culture or histologic proof. Prompt diagnosis and treatment are important to prevent serious bone and joint destruction