Nowadays which emergency contraception? Comparison between past and present: latest news in terms of clinical efficacy, side effects and contraindications

Despite many highly effective methods of contraception are available nowadays, many pregnancies are unintended. Emergency contraception (EC) is the use of drug or device after unprotected intercourse to prevent an unwanted pregnancy. It is a woman's last chance to prevent unintended pregnancy. Nevertheless the confusion about mechanisms of action, side effects, clinical efficacy and controindications makes the intervention underused in every setting investigated. So far levonorgestrel (LNG) has been considered the gold standard for oral EC. Today, a new type of second generation progesterone receptor modulator, ulipristal acetate (UPA) has been proposed as a more effective drug than LNG in prevention of unwanted pregnancies by delaying or inhibiting ovulation; even if many other devices are disposable in commerce. We revised the literature to concern most of the data available on the role of EC and moreover clarifying the available methods, the action windows of the accessible devices, the adverse events and the controindications.     

Space flight effects on bacterial physiology

The study of bacterial behavior under space flight conditions is highly important for the early detection of changes in bacterial communities and bacteria with medical, environmental, or life support consequences for survival of the crew in closed space environments. Although many species of prokaryotes have been studied in ground simulation facilities or have been flown in space flights, at present only few hard research data are available to predict the effects of cosmic radiation, microgravity, vibration and hypervelocity on microbial behavior in space flight. The results that are available tend to be fragmentary and often lack a classical, controlled experimental context to interpret them. Thus, many basic questions concerning the effects of space on microbial behavior have yet to be resolved.     

Electroporation: basic principles, practical considerations and applications in molecular biology

There are many approaches available for introducing foreign DNA into eukaryotes and prokaryotes. The most commonly used technique and currently of more practical interest is the electroporation. This review will focus on the electroporation as a promising, highly efficient and effective means of gene transfer. We summarize a detailed assessment of the various parameters and conditions that govern electroporation of a wide range of cell types.     

Efficient and specific removal of albumin from human serum samples

Patient serum or plasma is frequently monitored for biochemical markers of disease or physiological status. Many of the rapidly evolving technologies of proteome analysis are being used to find additional clinically informative protein markers. The unusually high abundance of albumin in serum can interfere with the resolution and sensitivity of many proteome profiling techniques. We have used monoclonal antibodies against human serum albumin (HSA) to develop an immunoaffinity resin that is effective in the removal of both full-length HSA and many of the HSA fragments present in serum. This resin shows markedly better performance than dye-based resins in terms of both the efficiency and specificity of albumin removal. Immunoglobulins are another class of highly abundant serum protein. When protein G resin is used together with our immunoaffinity resin, Ig proteins and HSA can be removed in a single step. This strategy could be extended to the removal of any protein for which specific antibodies or affinity reagents are available.     

A simple and ultra-low cost homemade seamless ligation cloning extract (SLiCE) as an alternative to a commercially available seamless DNA cloning kit

The seamless ligation cloning extract (SLiCE) method is a novel seamless DNA cloning tool that utilizes homologous recombination activities in Escherichia coli cell lysates to assemble DNA fragments into a vector. Several laboratory E. coli strains can be used as a source for the SLiCE extract; therefore, the SLiCE-method is highly cost-effective.The SLiCE has sufficient cloning ability to support conventional DNA cloning, and can simultaneously incorporate two unpurified DNA fragments into vector. Recently, many seamless DNA cloning kits have become commercially available; these are generally very convenient, but expensive. In this study, we evaluated the cloning efficiencies between a simple and highly cost-effective SLiCE-method and a commercial kit under various molar ratios of insert DNA fragments to vector DNA. This assessment identified that the SLiCE from a laboratory E. coli strain yielded 30?85% of the colony formation rate of a commercially available seamless DNA cloning kit. The cloning efficiencies of both methods were highly effective, exhibiting over 80% success rate under all conditions examined. These results suggest that SLiCE from a laboratory E. coli strain can efficiently function as an effective alternative to commercially available seamless DNA cloning kits.     

Cancer immunotherapy: the past,the present and the future

One of the most controversial issues in immunology for over a century has been whether an effective immune response can be elicited against malignant tumours. Whether the immunology community has believed cancer immunotherapy is feasible or impossible has been largely determined by the prevailing immunological paradigms at that time. In fact, during the last 110 years it is possible to trace at least five dramatic fluctuations in attitude towards cancer immunotherapy. It now appears, however, that overwhelming evidence is available to support the view that both the innate and adaptive immune responses can recognize and eliminate tumours. On the other hand, it remains to be seen if these immune responses can be harnessed to control cancer as, at the time of diagnosis, many tumours have already been immunoselected to be highly resistant to immune elimination. Based on these observations it is argued that immunotherapy approaches, other than the generation of tumour-specific cytotoxic T lymphocytes, must be explored. Alternative strategies include recruiting tumouricidal myeloid cells into tumours, generating antiangiogenic immune responses and directing innate immunity to hypoxia-induced ligands on tumour cells.     

A vaccine against Asian schistosomiasis

There is continued transmission of schistosomiasis japonica in China and Philippines despite highly effective control programs that focus on the application of the highly effective drug praziquantel (PZQ). The massive Three Gorges Dam across the Yangtze River in Southern China, soon to be completed, is expected to significantly increase schistosomiasis transmission and introduce the disease into areas currently unaffected. After long-term experience it is generally accepted that PZQ chemotherapy, although the cornerstone of current control programs, does have significant limitations. Furthermore, efficient drug delivery requires a substantial infrastructure to regularly cover all parts of an endemic area. Although there is not yet clear-cut evidence for the existence of PZQ-resistant schistosome strains, decreased susceptibility to the drug has been observed in several countries. As a result, a protective vaccine represents an essential component for the long-term control of schistosomiasis. This article briefly reviews aspects of anti-schistosome protective immunity that are important in the context of vaccine development. The current status in the development of vaccines against Schistosoma japonicum will then be discussed as will new approaches that may improve on the efficacy of available vaccines, and aid in the identification of new targets for immune attack. With new and extensive data becoming available from the S. japonicum genome project, the prospects for developing an effective vaccine are encouraging. The challenges that remain are many but it is crucial that the momentum towards developing effective anti-schistosome vaccines is maintained.     

Dot-blot-SNP analysis for practical plant breeding and cultivar identification in rice

We report dot-blot hybridization with allele-specific oligonucleotides for single nucleotide polymorphisms (SNPs) analysis to be applicable for practical plant breeding and cultivar identification. Competitive hybridization of a digoxigenin-labeled oligonucleotide having the sequence of a mutant allele (or a wild-type allele) together with an unlabeled oligonucleotide having the sequence of a wild-type allele (or a mutant allele) was highly effective to reduce background signals in dot-blot hybridization. All 100 tested genes (200 alleles) in rice having SNPs or insertions/deletions were detected in an allele-specific manner. Genotypes of 43 rice cultivars were identified by this technique, and eight SNP markers were found to be sufficient for distinguishing all the cultivars from each other. Dot-blot analysis was also applied to genotyping of Wx and Sd1 of F₄ plants in a conventional breeding program. Since dot-blot analysis with competitive hybridization provides a highly reliable, simple, and cost-effective technique for SNP analysis of a large number of samples, this technique is expected to realize the practical use of a novel breeding method, in which plants or breeding lines are selected by SNP analyses of many genes in a laboratory.Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.     

Effects of genetically modified human skin fibroblasts,stably overexpressing hepatocyte growth factor,on hepatic functions of cocultured C3A cells

Diseases leading to terminal hepatic failure are among the most common causes of death worldwide. Transplant of the whole organ is the only effective method to cure liver failure. Unfortunately, this treatment option is not available universally due to the serious shortage of donors. Thus, alternative methods have been developed that are aimed at prolonging the life of patients, including hepatic cells transplantation and bridging therapy based on hybrid bioartificial liver devices. Parenchymal liver cells are highly differentiated and perform many complex functions, such as detoxification and protein synthesis. Unfortunately, isolated hepatocytes display a rapid decline in viability and liver‐specific functions. A number of methods have been developed to maintain hepatocytes in their highly differentiated state in vitro, amongst them the most promising being 3D growth scaffolds and decellularized tissues or coculture with other cell types required for the heterotypic cell‐cell interactions. Here we present a novel approach to the hepatic cells culture based on the feeder layer cells genetically modified using lentiviral vector to stably produce additional amounts of hepatocyte growth factor and show the positive influence of these coculture conditions on the preservation of the hepatic functions of the liver parenchymal cells' model—C3A cells.     

Differences between pair-wise and multi-sequence alignment methods affect vertebrate genome comparisons

Producing complete and accurate alignments of multiple genomic sequences is complex and prone to errors, especially with sequences generated from highly diverged species. In this article, we show that multi-sequence (as opposed to pair-wise) alignment methods are substantially better at aligning (or 'capturing') all of the available orthologous sequence from phylogenetically diverse vertebrates (i.e. those separated by relatively long branch lengths). Maximum gains are obtained only when sequences from many species are aligned. Such multi-sequence alignments contain significant amounts of exonic and highly conserved non-exonic sequences that are not captured in pair-wise alignments, thus illustrating the importance of the alignment method used for performing comparative genome analyses.     

Therapy of ankylosing spondylitis and other spondyloarthritides: established medical treatment,anti-TNF-alpha therapy and other novel approaches

Therapeutic options for patients with more severe forms of spondyloarthritis (SpA) have been rather limited in recent decades. There is accumulating evidence that anti-tumor-necrosis-factor (anti-TNF) therapy is highly effective in SpA, especially in ankylosing spondylitis and psoriatic arthritis. The major anti-TNF-alpha agents currently available, infliximab (Remicade(R)) and etanercept (Enbrel(R)), are approved for the treatment of rheumatoid arthritis (RA) in many countries. In ankylosing spondylitis there is an unmet medical need, since there are almost no disease-modifying antirheumatic drugs (DMARDs) available for severely affected patients, especially those with spinal manifestations. Judging from recent data from more than 300 patients with SpA, anti-TNF therapy seems to be even more effective in SpA than in rheumatoid arthritis. However, it remains to be shown whether patients benefit from long-term treatment, whether radiological progression and ankylosis can be stopped and whether long-term biologic therapy is safe.     

Approaches to the therapy of rheumatoid arthritis

The treatment of RA is generally empirical. While there are many effective agents available, there are no agents that are curative. Progressive disease is frequently seen even in patients who are responsive to current therapies. Newer, more effective therapies are needed. The most promising area for new treatments appears to be specific biologic approaches with monoclonal antibodies or stimulants or inhibitors of lymphocytokines.     

I/NI-calls for the exclusion of non-informative genes: a highly effective filtering tool for microarray data

MOTIVATION: DNA microarray technology typically generates many measurements of which only a relatively small subset is informative for the interpretation of the experiment. To avoid false positive results, it is therefore critical to select the informative genes from the large noisy data before the actual analysis. Most currently available filtering techniques are supervised and therefore suffer from a potential risk of overfitting. The unsupervised filtering techniques, on the other hand, are either not very efficient or too stringent as they may mix up signal with noise. We propose to use the multiple probes measuring the same target mRNA as repeated measures to quantify the signal-to-noise ratio of that specific probe set. A Bayesian factor analysis with specifically chosen prior settings, which models this probe level information, is providing an objective feature filtering technique, named informative/non-informative calls (I/NI calls). RESULTS: Based on 30 real-life data sets (including various human, rat, mice and Arabidopsis studies) and a spiked-in data set, it is shown that I/NI calls is highly effective, with exclusion rates ranging from 70% to 99%. Consequently, it offers a critical solution to the curse of high-dimensionality in the analysis of microarray data. AVAILABILITY: This filtering approach is publicly available as a function implemented in the R package FARMS (www.bioinf.jku.at/software/farms/farms.html).     

Predicting Drug-Target Interactions for New Drug Compounds Using a Weighted Nearest Neighbor Profile

In silico discovery of interactions between drug compounds and target proteins is of core importance for improving the efficiency of the laborious and costly experimental determination of drug-target interaction. Drug-target interaction data are available for many classes of pharmaceutically useful target proteins including enzymes, ion channels, GPCRs and nuclear receptors. However, current drug-target interaction databases contain a small number of drug-target pairs which are experimentally validated interactions. In particular, for some drug compounds (or targets) there is no available interaction. This motivates the need for developing methods that predict interacting pairs with high accuracy also for these ''new'' drug compounds (or targets). We show that a simple weighted nearest neighbor procedure is highly effective for this task. We integrate this procedure into a recent machine learning method for drug-target interaction we developed in previous work. Results of experiments indicate that the resulting method predicts true interactions with high accuracy also for new drug compounds and achieves results comparable or better than those of recent state-of-the-art algorithms. Software is publicly available at http://cs.ru.nl/~tvanlaarhoven/drugtarget2013/.     

Repseek, a tool to retrieve approximate repeats from large DNA sequences

Chromosomes or other long DNA sequences contain many highly similar repeated sub-sequences. While there are efficient methods for detecting strict repeats or detecting already characterized repeats, there is no software available for detecting approximate repeats in large DNA sequences allowing for weighted substitutions and indels in a coherent statistical framework. Here, we present an implementation of a two-steps method (seed detection followed by their extension) that detects those approximate repeats. Our method is computationally efficient enough to handle large sequences and is flexible enough to account for influencing factors, such as sequence-composition biases both at the seed detection and alignment levels. AVAILABILITY: http://wwwabi.snv.jussieu.fr/public/RepSeek/     

Using ERDS to Infer Copy-Number Variants in High-Coverage Genomes

Although there are many methods available for inferring copy-number variants (CNVs) from next-generation sequence data, there remains a need for a system that is computationally efficient but that retains good sensitivity and specificity across all types of CNVs. Here, we introduce a new method, estimation by read depth with single-nucleotide variants (ERDS), and use various approaches to compare its performance to other methods. We found that for common CNVs and high-coverage genomes, ERDS performs as well as the best method currently available (Genome STRiP), whereas for rare CNVs and high-coverage genomes, ERDS performs better than any available method. Importantly, ERDS accommodates both unique and highly amplified regions of the genome and does so without requiring separate alignments for calling CNVs and other variants. These comparisons show that for genomes sequenced at high coverage, ERDS provides a computationally convenient method that calls CNVs as well as or better than any currently available method.     

Utility of different gene enrichment approaches toward identifying and sequencing the maize gene space

Maize (Zea mays) possesses a large, highly repetitive genome, and subsequently a number of reduced-representation sequencing approaches have been used to try and enrich for gene space while eluding difficulties associated with repetitive DNA. This article documents the ability of publicly available maize expressed sequence tag and Genome Survey Sequences (GSSs; many of which were isolated through the use of reduced representation techniques) to recognize and provide coverage of 78 maize full-length cDNAs (FLCs). All 78 FLCs in the dataset were identified by at least three GSSs, indicating that the majority of maize genes have been identified by at least one currently available GSS. Both methyl-filtration and high-Cot enrichment methods provided a 7- to 8-fold increase in gene discovery rates as compared to random sequencing. The available maize GSSs aligned to 75% of the FLC nucleotides used to perform searches, while the expressed sequence tag sequences aligned to 73% of the nucleotides. Our data suggest that at least approximately 95% of maize genes have been tagged by at least one GSS. While the GSSs are very effective for gene identification, relatively few (18%) of the FLCs are completely represented by GSSs. Analysis of the overlap of coverage and bias due to position within a gene suggest that RescueMu, methyl-filtration, and high-Cot methods are at least partially nonredundant.     

Therapy of ankylosing spondylitis and other spondyloarthritides: established medical treatment, anti-TNF-α therapy and other novel approaches

Therapeutic options for patients with more severe forms of spondyloarthritis (SpA) have been rather limited in recent decades. There is accumulating evidence that anti-tumor-necrosis-factor (anti-TNF) therapy is highly effective in SpA, especially in ankylosing spondylitis and psoriatic arthritis. The major anti-TNF-α agents currently available, infliximab (Remicade^®) and etanercept (Enbrel^®), are approved for the treatment of rheumatoid arthritis (RA) in many countries. In ankylosing spondylitis there is an unmet medical need, since there are almost no disease-modifying antirheumatic drugs (DMARDs) available for severely affected patients, especially those with spinal manifestations. Judging from recent data from more than 300 patients with SpA, anti-TNF therapy seems to be even more effective in SpA than in rheumatoid arthritis. However, it remains to be shown whether patients benefit from long-term treatment, whether radiological progression and ankylosis can be stopped and whether long-term biologic therapy is safe.     

Solvent accessibility, residue charge and residue volume, the three ingredients of a robust amino acid substitution matrix

Cost measure matrices or different amino acid indices have been widely used for studies in many fields of biology. One major criticism of these studies might be based on the unavailability of an unbiased and yet effective amino acid substitution matrix. Throughout this study we have devised a cost measure matrix based on the solvent accessibility, residue charge, and residue volume indices. Performed analyses on this novel substitution matrix (i.e. solvent accessibility charge volume (SCV) matrix) support the uncontaminated nature of this matrix regarding the genetic code. Although highly similar to a number of previously available cost measure matrices, the SCV matrix results in a more significant optimality in the error-buffering capacity of the genetic code when compared to many other amino acid substitution matrices. Besides, a method to compare an SCV-based scoring matrix with a number of widely used matrices has been devised, the results of which highlights the robustness of this matrix in protein family discrimination.