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الفكر في الصين اليوم
تناول الكتاب الفكر حول الصين اليوم حيث أنه خلال القرون الثلاثة الأخيرة التي شهدت تكون الحداثة الغربية وسيطرتها، تكونت عن الصين وترسخت صورة صين صاحبة كتابة رمزية، خاضعة لموروث استبدادي، معزولة عن سائر بقاع العالم، طوال قرون، وهو ما يفسر جمودها الفلسفي والسياسي والعلمي الذي جاء الغرب في الوقت المناسب لإيقاظها منه. فحين ننظر إلى كل هذه الترهات، سوف نجدها، بالتأكيد، بصيغ مختلفة وعلى مستويات متفاوتة التنميق، في عدد لا بأس به من المؤلفات الرائجة. وعلينا أن نضيف أن هذه المؤلفات لم تعدم، في المقابل، أن تمارس تأثيرا كبيرا في طريقة النخب الصينية تنظر بها إلى ثقافتها الخاصة، سواء في انتقاد الذات أو، خلافا لذلك كما هو الحال منذ فترة وجيزة، في مدح هذه الذات مدحا معززا بشعور قومي متزايد النخوة.
Book
Sequencing DNA with nanopores: Troubles and biases
Oxford Nanopore Technologies’ (ONT) long read sequencers offer access to longer DNA fragments than previous sequencer generations, at the cost of a higher error rate. While many papers have studied read correction methods, few have addressed the detailed characterization of observed errors, a task complicated by frequent changes in chemistry and software in ONT technology. The MinION sequencer is now more stable and this paper proposes an up-to-date view of its error landscape, using the most mature flowcell and basecaller. We studied Nanopore sequencing error biases on both bacterial and human DNA reads. We found that, although Nanopore sequencing is expected not to suffer from GC bias, it is a crucial parameter with respect to errors. In particular, low-GC reads have fewer errors than high-GC reads (about 6% and 8% respectively). The error profile for homopolymeric regions or regions with short repeats, the source of about half of all sequencing errors, also depends on the GC rate and mainly shows deletions, although there are some reads with long insertions. Another interesting finding is that the quality measure, although over-estimated, offers valuable information to predict the error rate as well as the abundance of reads. We supplemented this study with an analysis of a rapeseed RNA read set and shown a higher level of errors with a higher level of deletion in these data. Finally, we have implemented an open source pipeline for long-term monitoring of the error profile, which enables users to easily compute various analysis presented in this work, including for future developments of the sequencing device. Overall, we hope this work will provide a basis for the design of better error-correction methods.
Journal Article
The genomic basis of the Streptococcus thermophilus health-promoting properties
Background
Streptococcus thermophilus
is a Gram-positive bacterium widely used as starter in the dairy industry as well as in many traditional fermented products. In addition to its technological importance, it has also gained interest in recent years as beneficial bacterium due to human health-promoting functionalities. The objective of this study was to inventory the main health-promoting properties of
S. thermophilus
and to study their intra-species diversity at the genomic and genetic level within a collection of representative strains.
Results
In this study various health-related functions were analyzed at the genome level from 79 genome sequences of strains isolated over a long time period from diverse products and different geographic locations. While some functions are widely conserved among isolates (e.g., degradation of lactose, folate production) suggesting their central physiological and ecological role for the species, others including the tagatose-6-phosphate pathway involved in the catabolism of galactose, and the production of bioactive peptides and gamma-aminobutyric acid are strain-specific. Most of these strain-specific health-promoting properties seems to have been acquired via horizontal gene transfer events. The genetic basis for the phenotypic diversity between strains for some health related traits have also been investigated. For instance, substitutions in the
galK
promoter region correlate with the ability of some strains to catabolize galactose via the Leloir pathway. Finally, the low occurrence in
S. thermophilus
genomes of genes coding for biogenic amine production and antibiotic resistance is also a contributing factor to its safety status.
Conclusions
The natural intra-species diversity of
S. thermophilus
, therefore, represents an interesting source for innovation in the field of fermented products enriched for healthy components that can be exploited to improve human health. A better knowledge of the health-promoting properties and their genomic and genetic diversity within the species may facilitate the selection and application of strains for specific biotechnological and human health-promoting purpose. Moreover, by pointing out that a substantial part of its functional potential still defies us, our work opens the way to uncover additional health-related functions through the intra-species diversity exploration of
S. thermophilus
by comparative genomics approaches.
Journal Article
Quality of life after trigeminal nerve block in refractory trigeminal neuralgia: A retrospective cohort study and literature review
Objective
To evaluate the effect of trigeminal nerve block (TNB) on patients’ quality of life (QOL) 15 days after the procedure in patients with refractory TN.
Methods
This retrospective observational cohort study involved patients receiving TNB (levobupivacaine, clonidine, corticosteroid) between 2014 and 2018 at a postoperative pain clinic in France. Change in QOL from Day 0 (before block) to Day 15 was assessed according to SF-12.
Results
21 patients (62 ± 14 y) were included in the study. Most patients (71%) were referred following surgery or dentistry. Of the 9 patients (43%) who exhibited >10% increase in SF-12 scores and so were deemed responders, SF12-physical and SF12-mental were increased by mean differences of 17 and 9 points, respectively. The mean duration of block lasted 15 ± 59 days (range 1 to 90 days) and no severe adverse effects were observed.
Conclusion
Improved QOL was observed in approximately 50% of patients with trigeminal neuralgia (TN) two weeks after specific nerve block. The technique was easy to administer and well accepted by the patients.
Journal Article
Aspirin or Ticagrelor in Staphylococcus aureus Infective Endocarditis: Where Do We Stand?
Infective endocarditis is a challenging disease with a high mortality and morbidity rate. Antibiotic prophylaxis is currently recommended in high-risk infective endocarditis patients. However, the use of antibiotics faces the challenge of a low efficacy and contributes further to the emerging infection rate by antibiotic-resistant strains, emphasizing the need for new therapeutic strategies. Platelets are essential in the initial phase of infective endocarditis, acting as first-line immune responders. During the first phase of disease, bacteria can interact with platelets and counteract platelet antimicrobial activities. Mechanistic in vitro and animal studies on the effect of aspirin on bacteria-platelet interactions and the prevention of vegetation development showed promising results. However, data from clinical studies on the outcome of infective endocarditis patients who were receiving medically indicated aspirin therapy remain controversial. Therefore, the benefit of antiplatelet agents in infective endocarditis prevention has been questioned. Besides aspirin, it has been discovered that the platelet P2Y12 receptor antagonist ticagrelor has antibacterial properties in addition to its potent antiplatelet activity. Furthermore, a recent study in mice and a case report remarkably indicated the ability of this drug to eradicate Staphylococcus aureus bacteremia. This review will focus on current knowledge on antibacterial activity of ticagrelor, compared to aspirin, pointing out main unanswered questions. The goal is to provide food for thought as to whether a prior ticagrelor therapy might be beneficial for the prevention of infective endocarditis.
Journal Article
Ticagrelor alters the membrane of Staphylococcus aureus and enhances the activity of vancomycin and daptomycin without eliciting cross-resistance
Infections with multidrug-resistant bacteria pose a major healthcare problem with an urgent need for novel treatment options. The antiplatelet drug ticagrelor possesses antibacterial activity against Gram-positive bacteria including methicillin-resistant and vancomycin-resistant Staphylococcus aureus strains. We report a unique, dose-dependent, antibacterial mechanism of action of ticagrelor, which alters the properties and integrity of the bacterial cytoplasmic membrane. Ticagrelor retains activity against multidrug-resistant staphylococci, including isolates carrying the most common in vivo selected daptomycin resistance mutations and vancomycin-intermediate Staphylococcus aureus . Our data support the use of ticagrelor as adjunct therapy against multidrug-resistant strains. Because of the presence of multiple non-protein targets of this drug within the bacterial membrane, resistance development is expected to be slow. All these findings corroborate the accumulating observational clinical evidence for a beneficial anti-bacterial effect of ticagrelor in cardiovascular patients in need of such treatment.
Journal Article
An Extended Network of Genomic Maintenance in the Archaeon Pyrococcus abyssi Highlights Unexpected Associations between Eucaryotic Homologs
In Archaea, the proteins involved in the genetic information processing pathways, including DNA replication, transcription, and translation, share strong similarities with those of eukaryotes. Characterizations of components of the eukaryotic-type replication machinery complex provided many interesting insights into DNA replication in both domains. In contrast, DNA repair processes of hyperthermophilic archaea are less well understood and very little is known about the intertwining between DNA synthesis, repair and recombination pathways. The development of genetic system in hyperthermophilic archaea is still at a modest stage hampering the use of complementary approaches of reverse genetics and biochemistry to elucidate the function of new candidate DNA repair gene. To gain insights into genomic maintenance processes in hyperthermophilic archaea, a protein-interaction network centred on informational processes of Pyrococcus abyssi was generated by affinity purification coupled with mass spectrometry. The network consists of 132 interactions linking 87 proteins. These interactions give insights into the connections of DNA replication with recombination and repair, leading to the discovery of new archaeal components and of associations between eucaryotic homologs. Although this approach did not allow us to clearly delineate new DNA pathways, it provided numerous clues towards the function of new molecular complexes with the potential to better understand genomic maintenance processes in hyperthermophilic archaea. Among others, we found new potential partners of the replication clamp and demonstrated that the single strand DNA binding protein, Replication Protein A, enhances the transcription rate, in vitro, of RNA polymerase. This interaction map provides a valuable tool to explore new aspects of genome integrity in Archaea and also potentially in Eucaryotes.
Journal Article
Modelling of the behaviour of metal foams under shock compression
A theoretical modelling is proposed to describe the shock response of foam materials. This model is based on micromechanical and energetic arguments, and takes into account the contribution of microscale inertia. Within this framework, an analytical expression of the Hugoniot stress-strain curve is proposed for elastic-plastic cellular materials. The predictions derived from the proposed model are in excellent agreement with experimental data for open-cell aluminium foams. The case of viscoplastic foams is also considered.
Journal Article
Bioinformatic prediction, deep sequencing of microRNAs and expression analysis during phenotypic plasticity in the pea aphid, Acyrthosiphon pisum
Background
Post-transcriptional regulation in eukaryotes can be operated through microRNA (miRNAs) mediated gene silencing. MiRNAs are small (18-25 nucleotides) non-coding RNAs that play crucial role in regulation of gene expression in eukaryotes. In insects, miRNAs have been shown to be involved in multiple mechanisms such as embryonic development, tissue differentiation, metamorphosis or circadian rhythm. Insect miRNAs have been identified in different species belonging to five orders: Coleoptera, Diptera, Hymenoptera, Lepidoptera and Orthoptera.
Results
We developed high throughput Solexa sequencing and bioinformatic analyses of the genome of the pea aphid
Acyrthosiphon pisum
in order to identify the first miRNAs from a hemipteran insect. By combining these methods we identified 149 miRNAs including 55 conserved and 94 new miRNAs. Moreover, we investigated the regulation of these miRNAs in different alternative morphs of the pea aphid by analysing the expression of miRNAs across the switch of reproduction mode. Pea aphid microRNA sequences have been posted to miRBase:
http://microrna.sanger.ac.uk/sequences/
Conclusions
Our study has identified candidates as putative regulators involved in reproductive polyphenism in aphids and opens new avenues for further functional analyses.
Journal Article
Symbiotic Virus at the Evolutionary Intersection of Three Types of Large DNA Viruses; Iridoviruses, Ascoviruses, and Ichnoviruses
Background: The ascovirus, DpAV4a (family Ascoviridae), is a symbiotic virus that markedly increases the fitness of its vector, the parasitic ichneumonid wasp, Diadromus puchellus, by increasing survival of wasp eggs and larvae in their lepidopteran host, Acrolepiopsis assectella. Previous phylogenetic studies have indicated that DpAV4a is related to the pathogenic ascoviruses, such as the Spodoptera frugiperda ascovirus 1a (SfAV1a) and the lepidopteran iridovirus (family Iridoviridae), Chilo iridescent virus (CIV), and is also likely related to the ancestral source of certain ichnoviruses (family Polydnaviridae). Methodology/Principal Findings: To clarify the evolutionary relationships of these large double-stranded DNA viruses, we sequenced the genome of DpAV4a and undertook phylogenetic analyses of the above viruses and others, including iridoviruses pathogenic to vertebrates. The DpAV4a genome consisted of 119,343 bp and contained at least 119 open reading frames (ORFs), the analysis of which confirmed the relatedness of this virus to iridoviruses and other ascoviruses. Conclusions: Analyses of core DpAV4a genes confirmed that ascoviruses and iridoviruses are evolutionary related. Nevertheless, our results suggested that the symbiotic DpAV4a had a separate origin in the iridoviruses from the pathogenic ascoviruses, and that these two types shared parallel evolutionary paths, which converged with respect to virion structure (icosahedral to bacilliform), genome configuration (linear to circular), and cytopathology (plasmalemma blebbing to virion-containing vesicles). Our analyses also revealed that DpAV4a shared more core genes with CIV than with other ascoviruses and iridoviruses, providing additional evidence that DpAV4a represents a separate lineage. Given the differences in the biology of the various iridoviruses and ascoviruses studied, these results provide an interesting model for how viruses of different families evolved from one another.
Journal Article