The Motif of the Messiah in Zechariah 9-14

Topic Zechariah 9-14 is full of prophecies regarding the coming of the messiah. The Jews at the time of Jesus awaited a messiah different from the one that came but how so? Did they misunderstand the prophecies or, by any chance, were the prophecies not clear enough? Purpose Firstly, it will be given an overview of the Book of Zechariah. Then, the messianic prophecies in Zechariah 9-14 will be examined closer and how they fit into the context of the prophets, the book of Zechariah, and the different chapters. An analysis of the similarities and differences will be written afterwards. Then Jewish expectation will be analysed. Afterwards, a conclusion will be drawn. Sources To have an in-depth study of the Texts of Zechariah, each messianic prophecy is translated with my own words from Hebrew into English. The context of the prophecies will be closer examined and the most recent and important commentaries will be considered. To understand the Jewish expectation of the messiah, Jewish literature and statements of Rabbis will be considered before a conclusion will be drawn. Conclusions The in-depth study of Zechariah showed that the messianic prophecies are in fact always in a military and judgment setting. However, it is not the messiah who acts belligerent, but it is the Lord who is fighting for his people. Zechariah shows that the messiah, was supposed to come as someone who restores the leadership and the nation, someone who restores the spiritual constitution. After this is accomplished, the restoration of the land will be the next goal. The Jews did not recognize their messiah because they did not anticipate forgiveness of their sins

Plant-symbiotic fungi as chemical engineers: multi-genome analysis of the Clavicipitaceae reveals dynamics of alkaloid Loci

The fungal family Clavicipitaceae includes plant symbionts and parasites that produce several psychoactive and bioprotective alkaloids. The family includes grass symbionts in the epichloae clade (Epichloë and Neotyphodium species), which are extraordinarily diverse both in their host interactions and in their alkaloid profiles. Epichloae produce alkaloids of four distinct classes, all of which deter insects, and some—including the infamous ergot alkaloids—have potent effects on mammals. The exceptional chemotypic diversity of the epichloae may relate to their broad range of host interactions, whereby some are pathogenic and contagious, others are mutualistic and vertically transmitted (seed-borne), and still others vary in pathogenic or mutualistic behavior. We profiled the alkaloids and sequenced the genomes of 10 epichloae, three ergot fungi (Claviceps species), a morning-glory symbiont (Periglandula ipomoeae), and a bamboo pathogen (Aciculosporium take), and compared the gene clusters for four classes of alkaloids. Results indicated a strong tendency for alkaloid loci to have conserved cores that specify the skeleton structures and peripheral genes that determine chemical variations that are known to affect their pharmacological specificities. Generally, gene locations in cluster peripheries positioned them near to transposon-derived, AT-rich repeat blocks, which were probably involved in gene losses, duplications, and neofunctionalizations. The alkaloid loci in the epichloae had unusual structures riddled with large, complex, and dynamic repeat blocks. This feature was not reflective of overall differences in repeat contents in the genomes, nor was it characteristic of most other specialized metabolism loci. The organization and dynamics of alkaloid loci and abundant repeat blocks in the epichloae suggested that these fungi are under selection for alkaloid diversification. We suggest that such selection is related to the variable life histories of the epichloae, their protective roles as symbionts, and their associations with the highly speciose and ecologically diverse cool-season grasses

Niveau de preuve du suivi therapeutique pharmacologique de la ribavirine

La ribavirine, traitement antiviral standard de l’hépatite C chronique, utilisée en association avec l’interféron alpha pégylé, présente une importante variabilité pharmacocinétique inter-individuelle. La ribavirine est responsable d’une anémie très fréquente. Au vu des données de la littérature, un suivi thérapeutique pharmacologique (STP) peut il être proposé pour la ribavirine ? Plusieurs études ont été menées chez des patients chroniquement infectés par le virus de l’hépatite C (VHC) ou co-infecté VIH-VHC pour établir l’intérêt du STP de la ribavirine. La réponse virologique soutenue (RVS), qui se définit par l’obtention d’une charge virale indétectable 6 mois après l’arrêt du traitement, est significativement associée à la concentration plasmatique résiduelle (Cmin), mesurée à S4, avec des valeurs variant entre 2 et 3 μg/mL. Concernant le lien exposition-toxicité, il existe une relation non linéaire entre la concentration plasmatique en ribavirine et la sévérité de l’anémie présentée par les patients, avec une augmentation significative du risque de survenue associée à des concentrations de ribavirine >2 μg/mL. Des études non randomisées ont montré un gain en terme d’obtention de la RVS et de la gestion de la toxicité hématologique, permettant de proposer un niveau de preuve recommandé pour le STP de la ribavirine

Clin Pharmacol Ther

Boffito et al. recalled the critical importance to correctly interpret protein binding. Changes of lopinavir pharmacokinetics in COVID-19 are a perfect illustration. Indeed, several studies described that total lopinavir plasma concentrations were considerably higher in severe COVID-19 patients than those reported in HIV patients. These findings have led to a reduction of the dose of lopinavir in some patients, hypothetizing an inhibitory effect of inflammation on lopinavir metabolism. Unfortunately, changes in plasma protein binding were never investigated. We performed a retrospective cohort study. Data were collected from the medical records of patients hospitalized for COVID-19 treated with lopinavir/ritonavir in intensive care units or infectious disease departments of Toulouse university hospital (France). Total and unbound concentrations of lopinavir, C reactive protein, albumin and alpha-1-acid glycoprotein (AAG) levels were measured during routine care on the same samples. In COVID-19 patients, increased total lopinavir concentration is the result of an increased AAG-bound lopinavir concentration whereas the unbound concentration remains constant, and insufficient to reduce the SARS-CoV-2 viral load. Although international guidelines have recently recommended against using lopinavir/ritonavir to treat severe COVID-19, the description of lopinavir pharmacokinetics changes in COVID-19 is a textbook case of the high risk of misinterpretation of a total drug exposure when changes in protein binding are not taken into consideration

AtLAST Science Overview Report

International audienceSubmillimeter and millimeter wavelengths provide a unique view of the Universe, from the gas and dust that fills and surrounds galaxies to the chromosphere of our own Sun. Current single-dish facilities have presented a tantalising view of the brightest (sub-)mm sources, and interferometers have provided the exquisite resolution necessary to analyse the details in small fields, but there are still many open questions that cannot be answered with current facilities. In this report we summarise the science that is guiding the design of the Atacama Large Aperture Submillimeter Telescope (AtLAST). We demonstrate how tranformational advances in topics including star formation in high redshift galaxies, the diffuse circumgalactic medium, Galactic ecology, cometary compositions and solar flares motivate the need for a 50m, single-dish telescope with a 1-2 degree field of view and a new generation of highly multiplexed continuum and spectral cameras. AtLAST will have the resolution to drastically lower the confusion limit compared to current single-dish facilities, whilst also being able to rapidly map large areas of the sky and detect extended, diffuse structures. Its high sensitivity and large field of view will open up the field of submillimeter transient science by increasing the probability of serendipitous detections. Finally, the science cases listed here motivate the need for a highly flexible operations model capable of short observations of individual targets, large surveys, monitoring programmes, target of opportunity observations and coordinated observations with other observatories. AtLAST aims to be a sustainable, upgradeable, multipurpose facility that will deliver orders of magnitude increases in sensitivity and mapping speeds over current and planned submillimeter observatories

Deciphering the cryptic genome: Genome-wide analyses of the rice pathogen <em>Fusarium fujikuroi</em> reveal complex regulation of secondary metabolism and novel metabolites.

The fungus Fusarium fujikuroi causes &ldquo;bakanae&rdquo; disease of rice due to its ability to produce gibberellins (GAs), but it is also known for producing harmful mycotoxins. However, the genetic capacity for the whole arsenal of natural compounds and their role in the fungus&#39; interaction with rice remained unknown. Here, we present a high-quality genome sequence of F. fujikuroi that was assembled into 12 scaffolds corresponding to the 12 chromosomes described for the fungus. We used the genome sequence along with ChIP-seq, transcriptome, proteome, and HPLC-FTMS-based metabolome analyses to identify the potential secondary metabolite biosynthetic gene clusters and to examine their regulation in response to nitrogen availability and plant signals. The results indicate that expression of most but not all gene clusters correlate with proteome and ChIP-seq data. Comparison of the F. fujikuroi genome to those of six other fusaria revealed that only a small number of gene clusters are conserved among these species, thus providing new insights into the divergence of secondary metabolism in the genus Fusarium. Noteworthy, GA biosynthetic genes are present in some related species, but GA biosynthesis is limited to F. fujikuroi, suggesting that this provides a selective advantage during infection of the preferred host plant rice. Among the genome sequences analyzed, one cluster that includes a polyketide synthase gene (PKS19) and another that includes a non-ribosomal peptide synthetase gene (NRPS31) are unique to F. fujikuroi. The metabolites derived from these clusters were identified by HPLC-FTMS-based analyses of engineered F. fujikuroi strains overexpressing cluster genes. In planta expression studies suggest a specific role for the PKS19-derived product during rice infection. Thus, our results indicate that combined comparative genomics and genome-wide experimental analyses identified novel genes and secondary metabolites that contribute to the evolutionary success of F. fujikuroi as a rice pathogen