Structure-activity studies of irumamycin type macrolides from Streptomyces sp. INA-Ac-5812
Three natural glycosylated macrolide compounds, known irumamycin 1 and X-14952B 2, as well as new
isoirumamycin 3, were isolated from ethyl acetate mycelium extract of Streptomyces sp. INA-Ac-5812.
Structures of the compounds were elucidated using 1D and 2D NMR. Isoirumamycin 3 was found to
be an isomer of irumamycin with an 18-membered macrolactone ring instead of 20-membered macrolide
in irumamycin. A previously unknown stereo configuration of irumamycin epoxide (C23, C24) and
hemiketal (C3, C7) fragments was deduced from NMR data (ROESY/NOESY and HSQMBC). Cytotoxic, antifungal
and antibacterial activities were studied for all isolated compounds. Comparison of the collected
data showed crucial importance of 20-membered macrolactone ring for antimicrobial properties of this
New biologically active substances isolated from natural sources provide valuable information on structural motifs that are important for a specifi c type of activity and can also be used as drugs or serve as raw materials for chemical modifi cation in order to develop new pharmaceuticals. This review considers natural antibiotics combining two pharmacophores in their structure: a redox-active naphthoquinone moiety and a membrane-active polyol macrolide. Data on their structures and the spectrum of biological activity are summarized.
One of the key advances in genome assembly that has led to a significant improvement in contig lengths has been improved algorithms for utilization of paired reads (mate-pairs). While in most assemblers, mate-pair information is used in a post-processing step, the recently proposed Paired de Bruijn Graph (PDBG) approach incorporates the mate-pair information directly in the assembly graph structure. However, the PDBG approach faces difficulties when the variation in the insert sizes is high. To address this problem, we first transform mate-pairs into edge-pair histograms that allow one to better estimate the distance between edges in the assembly graph that represent regions linked by multiple mate-pairs. Further, we combine the ideas of mate-pair transformation and PDBGs to construct new data structures for genome assembly: pathsets and pathset graphs.
Many environmental stimuli present a quasi-rhythmic structure at different timescales that the brain needs to decompose and integrate. Cortical oscillations have been proposed as instruments of sensory de-multiplexing, i.e., the parallel processing of different frequency streams in sensory signals. Yet their causal role in such a process has never been demonstrated. Here, we used a neural microcircuit model to address whether coupled theta–gamma oscillations, as observed in human auditory cortex, could underpin the multiscale sensory analysis of speech. We show that, in continuous speech, theta oscillations can flexibly track the syllabic rhythm and temporally organize the phoneme-level response of gamma neurons into a code that enables syllable identification. The tracking of slow speech fluctuations by theta oscillations, and its coupling to gamma-spiking activity both appeared as critical features for accurate speech encoding. These results demonstrate that cortical oscillations can be a key instrument of speech de-multiplexing, parsing, and encoding.
Papers about natural protection territories
Hypoxia of trophoblast cells is an important regulator of normal development of the placenta. However, some pathological states associated with hypoxia, e.g. preeclampsia, impair the functions of placental cells. Oxyquinoline derivative inhibits HIF-prolyl hydroxylase by stabilizing HIF-1 transcription complex, thus modeling cell response to hypoxia. In human choriocarcinoma cells BeWo b30 (trophoblast model), oxyquinoline increased the expression of a core hypoxia response genes along with up-regulation of NOS3, PDK1, and BNIP3 genes and down-regulation of the PPARGC1B gene. These changes in the expression profile attest to activation of the metabolic cell reprogramming mechanisms aimed at reducing oxygen consumption by enabling the switch from aerobic to anaerobic glucose metabolism and the respective decrease in number of mitochondria. The possibility of practical use of the therapeutic properties of oxyquinoline derivatives is discussed.