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841.
Md. Monirul Islam Shinobu Sato Shingo Shinozaki Shigeori Takenaka 《Bioorganic & medicinal chemistry letters》2017,27(2):329-335
To identify an effective ligand that binds to a G-quadruplex structure but not a double-stranded DNA (dsDNA), a set of biophysical and biochemical experiments were carried out using newly synthesized cyclic ferrocenylnaphthalene diimide (cFNDI, 1) or the non-cyclic derivative (2) with various structures of G-quadruplex DNAs and dsDNA. Compound 1 bound strongly to G-quadruplexes DNAs (106 M?1 order) with diminished binding to dsDNA (104 M?1 order) in 100 mM AcOH-AcOK buffer (pH 5.5) containing 100 mM KCl. Interestingly, 1 showed an approximately 50-fold higher selectivity to mixed hybrid-type telomeric G-quadruplex DNA (K = 3.4 × 106 M?1 and a 2:1 stoichiometry) than dsDNA (K = 7.5 × 104 M?1) did. Furthermore, 1 showed higher thermal stability to G-quadruplex DNAs than it did to dsDNA with a preference for c-kit and c-myc G-quadruplex DNAs over telomeric and thrombin binding aptamers. Additionally, 1 exhibited telomerase inhibitory activity with a half-maximal inhibitory concentration (IC50) of 0.4 μM. Compound 2 showed a preference for G-quadruplex; however, the binding affinity magnitude and preference were improved in 1 because the former had a cyclic structure. 相似文献
842.
Iram Parveen Naseem Ahmed Danish Idrees Parvez Khan Md. Imtaiyaz Hassan 《Bioorganic & medicinal chemistry letters》2017,27(18):4493-4499
Substituted 2-amino-7-((6-(4-(2-hydroxyethyl) piperazin-1-yl)-2-methylpyrimidin-4-yl)oxy)-4-phenyl-4H-chromene-3-carbonitriles and 2-amino-7-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)oxy)-4-phenyl-1,4-dihydroquinoline-3-carbonitriles were synthesized via an efficient multi-component one pot synthesis under mild conditions. These compounds 1–20 were evaluated against human breast cancer cell lines (MCF-7) and human embryonic kidney cells (HEK293) for cytotoxic activities. Among them, compounds 6, 7, 15, 17 and 19 showed better anti-proliferative activities as (IC50 value 48 ± 1.70, 65 ± 1.13, 92 ± 1.18, 30 ± 1.17 and 16 ± 1.10 µM) than curcumin drug (48 ± 1.11 µM). Molecular docking was also performed with active compounds 6, 7 and 15 against Bcl-2 protein which gave good binding affinity (ΔG = ?9.08, ?8.29 and ?7.70 kcal/mol) respectively. Furthermore, the structure-activity relationship (SAR) analysis revealed that the chromene and quinoline moieties, when attached with pyrimide and piperazine moieties, enhanced anti-proliferative activities. 相似文献
843.
How well documented is Australia's flora? Understanding spatial bias in vouchered plant specimens
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Md. Mohasinul Haque David A. Nipperess Rachael V. Gallagher Linda J. Beaumont 《Austral ecology》2017,42(6):690-699
Massive digitization of natural history collections (NHC) has opened the door for researchers to conduct inferential studies on the collection of biological diversity across space and time. The widespread use of NHCs in scientific research makes it essential to characterize potential sources of spatial bias. In this study, we assessed spatial patterns in records from the Australian Virtual Herbarium (AVH), based on >3 000 000 vouchered specimens of around 21 000 native plant species. The AVH is the main database for describing Australia's flora, and identifying its limitations is of paramount interest for the validity of conservation and environmental studies. We characterized how sampling effort is distributed across each Interim Bioregion of Australia (IBRA), then asked: (i) How complete are species inventories for each bioregion? We define completeness (C) as the ratio of observed to estimated species richness, using the Chao 1 estimator, (ii) How is sampling effort related to a commonly used Human Influence Index (HII)? and (iii) What is the probability that additional collections would result in the identification of previously unrecorded species in each bioregion? Sampling effort across bioregions is unequal, which partially reflects the collecting behaviour of naturalists in relation to species richness patterns. The density of records in bioregions ranges from 0.02–8.37 km?2. At the bioregional scale, completeness is generally high with 79% of bioregions estimated to have records for at least 80% of their species. Completeness is partly explained by sampling effort (r = 0.43, p = 0.01), although some bioregions (e.g. Northern Kimberley and Burt Plain) have high completeness yet relatively low sampling effort. The inventory of Hampton, however, is substantially less complete than other bioregions (C = 0.66). Bioregions with high HII consistently have high completeness, while regions with low HII span the full range of completeness values. We calculated that an additional specimen collected from a bioregion has a 0.33% (Wet Tropics) to 11.7% (Arnhem Coast) probability of representing a new species for that region. Our assessment can assist with directing future systematic survey efforts by identifying bioregions where additional surveying may result in the greatest return, in terms of increasing knowledge of species richness and diversity. 相似文献
844.
Rhamnose synthase activity is required for pathogenicity of the vascular wilt fungus Verticillium dahliae 总被引:1,自引:0,他引:1
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Parthasarathy Santhanam Jordi C. Boshoven Omar Salas Kyle Bowler Md Tohidul Islam Mojtaba Keykha Saber Grardy C. M. van den Berg Maor Bar‐Peled Bart P. H. J. Thomma 《Molecular Plant Pathology》2017,18(3):347-362
The initial interaction of a pathogenic fungus with its host is complex and involves numerous metabolic pathways and regulatory proteins. Considerable attention has been devoted to proteins that play a crucial role in these interactions, with an emphasis on so‐called effector molecules that are secreted by the invading microbe to establish the symbiosis. However, the contribution of other types of molecules, such as glycans, is less well appreciated. Here, we present a random genetic screen that enabled us to identify 58 novel candidate genes that are involved in the pathogenic potential of the fungal pathogen Verticillium dahliae, which causes vascular wilt diseases in over 200 dicotyledonous plant species, including economically important crops. One of the candidate genes that was identified concerns a putative biosynthetic gene involved in nucleotide sugar precursor formation, as it encodes a putative nucleotide‐rhamnose synthase/epimerase‐reductase (NRS/ER). This enzyme has homology to bacterial enzymes involved in the biosynthesis of the nucleotide sugar deoxy‐thymidine diphosphate (dTDP)‐rhamnose, a precursor of L‐rhamnose, which has been shown to be required for virulence in several human pathogenic bacteria. Rhamnose is known to be a minor cell wall glycan in fungi and has therefore not been suspected as a crucial molecule in fungal–host interactions. Nevertheless, our study shows that deletion of the VdNRS/ER gene from the V. dahliae genome results in complete loss of pathogenicity on tomato and Nicotiana benthamiana plants, whereas vegetative growth and sporulation are not affected. We demonstrate that VdNRS/ER is a functional enzyme in the biosynthesis of uridine diphosphate (UDP)‐rhamnose, and further analysis has revealed that VdNRS/ER deletion strains are impaired in the colonization of tomato roots. Collectively, our results demonstrate that rhamnose, although only a minor cell wall component, is essential for the pathogenicity of V. dahliae. 相似文献
845.
Syeda Shahnaz Parvez Mohammad Masud Parvez Yoshiharu Fujii Hiroshi Gemma 《Plant Growth Regulation》2004,42(3):245-252
Allelopathic performance of the bark and seed of Tamarindus indica L. tree was evaluated through bioassay-guided studies using seven common agronomic crops (asparagus, cucumber, lettuce, radish,
sesame, tomato and welsh onion) and seven weed species (barnyard grass, Chinese milk vetch, perennial ryegrass, phacelia,
timothy grass, white clover and wild ginger) under laboratory conditions. As demonstrated by a sandwich method, the bark of
the tamarind tree caused strong growth inhibition (compared to the corresponding controls) in both radicles and hypocotyls
of the species tested, and the inhibitory effect was highest in barnyard grass (52–65%) and lowest in welsh onion (19–13%).
The crude-water soluble extracts of bark at different concentrations (1, 5 and 10%) (w/v) exhibited a strong growth inhibition
in all the plant species tested, and a proportional increase in the percentage of growth inhibition was observed with an increase
in the concentrations of the extracts. The magnitude of inhibition in weed species was higher (5–60%) than those of agronomic
crop species (3–40%). The growth of all the weed species tested was strongly inhibited (17–56%), while the agronomic crop
species showed both inhibited (5–21%) and stimulated (5–27%) growth due to the effect of crude-water soluble exudates of tamarind
seed. Among the agronomic crop species tested, lettuce (22–27%) followed by radish (20–25%) and sesame (5–8%) showed stimulatory
growth with the crude-water soluble exudates of seed. In the pot culture experiments using four agronomic crops (lettuce,
radish, tomato and cucumber) and two weed species (barnyard grass and white clover), spraying of crude-water soluble extracts
of tamarind seed-coat at three different concentrations (1, 5 and 10%) (w/v) showed that the growth of lettuce (35–62%) and
radish (32–56%) was stimulated, while all other species tested showed growth inhibition (29–61%). When the spraying of crude
extracts of seed-coat was turned off, the growth of both lettuce and radish continued to be stimulated (4–7%) and all other
previously inhibited species recovered well, the recovery percentage ranging between 78 and 82%. However, when spraying of
crude extracts of seed-coat was continued, growth increased (10–14%) in lettuce and radish, and reduced (37–76%) in four other
species tested. The inhibitory or stimulatory effects of the crude extracts on agronomic crop and weed species were higher
in the radicle than the hypocotyl and reached a peak with 10% (w/v) concentrations. These results clearly demonstrated the
differential allelopathic effects (inhibitory and excitatory) of bark and seed of tamarind tree in the species tested. Thus,
it is evident that these two organs contain certain biologically active true growth regulator(s) and are either additively
or synergistically involved in the plant-specific expression, particularly by the seed-coat. 相似文献
846.
Md Torikul Islam Shelby A. Hall Tavia Dutson Samuel I. Bloom R. Colton Bramwell John Kim Jordan R. Tucker Daniel R. Machin Anthony J. Donato Lisa A. Lesniewski 《Aging cell》2024,23(2):e14040
Systemic inhibition of the mammalian target of rapamycin (mTOR) delays aging and many age-related conditions including arterial and metabolic dysfunction. However, the mechanisms and tissues involved in these beneficial effects remain largely unknown. Here, we demonstrate that activation of S6K, a downstream target of mTOR, is increased in arteries with advancing age, and that this occurs preferentially in the endothelium compared with the vascular smooth muscle. Induced endothelial cell-specific deletion of mTOR reduced protein expression by 60–70%. Although this did not significantly alter arterial and metabolic function in young mice, endothelial mTOR reduction reversed arterial stiffening and improved endothelium-dependent dilation (EDD) in old mice, indicating an improvement in age-related arterial dysfunction. Improvement in arterial function in old mice was concomitant with reductions in arterial cellular senescence, inflammation, and oxidative stress. The reduction in endothelial mTOR also improved glucose tolerance in old mice, and this was associated with attenuated hepatic gluconeogenesis and improved lipid tolerance, but was independent of alterations in peripheral insulin sensitivity, pancreatic beta cell function, or fasted plasma lipids in old mice. Lastly, we found that endothelial mTOR reduction suppressed gene expression of senescence and inflammatory markers in endothelial-rich (i.e., lung) and metabolically active organs (i.e., liver and adipose tissue), which may have contributed to the improvement in metabolic function in old mice. This is the first evidence demonstrating that reducing endothelial mTOR in old age improves arterial and metabolic function. These findings have implications for future drug development. 相似文献
847.
Hoonhee Seo Sukyung Kim Hafij Al Mahmud Md Imtiazul Islam Youjin Yoon Hyun-Deuk Cho Kung-Woo Nam Jiwon Choi Young Sig Gil Byung-Eui Lee Ho-Yeon Song 《PLoS biology》2022,20(5)
The continued spread of drug-resistant tuberculosis is one of the most pressing and complex challenges facing tuberculosis management worldwide. Therefore, developing a new class of drugs is necessary and urgently needed to cope with the increasing threat of drug-resistant tuberculosis. This study aims to discover a potential new class of tuberculosis drug candidates different from existing tuberculosis drugs. By screening a library of compounds, methyl (S)-1-((3-alkoxy-6,7-dimethoxyphenanthren-9-yl)methyl)-5-oxopyrrolidine-2-carboxylate (PP) derivatives with antitubercular activity were discovered. MIC ranges for PP1S, PP2S, and PP3S against clinically isolated drug-resistant Mycobacterium tuberculosis strains were 0.78 to 3.13, 0.19 to 1.56, and 0.78 to 6.25 μg/ml, respectively. PPs demonstrated antitubercular activities in macrophage and tuberculosis mouse models, showing no detectable toxicity in all assays tested. PPs specifically inhibited M. tuberculosis without significantly changing the intestinal microbiome in mice. Mutants selected in vitro suggest that the drug targets the PE-PGRS57, which has been found only in the genomes of the M. tuberculosis complex, highlighting the specificity and safety potency of this compound. As PPs show an excellent safety profile and highly selective toxicity specific to M. tuberculosis, PPs are considered a promising new candidate for the treatment of drug-resistant tuberculosis while maintaining microbiome homeostasis.This study identifies a new class of PP derivatives as Mycobacterium tuberculosis-targeting antimicrobials with microbiome-safe properties that do not disrupt normal flora, making them a promising candidate for the treatment of drug-resistant tuberculosis. 相似文献
848.
849.
850.
Zhonghao Chen Ying Zhang Meng Wang Md Sahidul Islam Ping Liao Yuanjia Hu Xin Chen 《International journal of biological sciences》2022,18(12):4629
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has undergone multiple mutations since its emergence, and its latest variant, Omicron (B.1.1.529), is the most contagious variant of concern (VOC) which poses a major and imminent threat to public health. Since firstly reported by World Health Organization (WHO) in November 2021, Omicron variant has been spreading rapidly and has become the dominant variant in many countries worldwide. Omicron is the most mutated variant so far, containing 60 mutations in its genome, including 37 mutations in the S-protein. Since all current COVID-19 vaccines in use were developed based on ancestral SARS-CoV-2 strains, whether they are protective against Omicron is a critical question which has been the center of study currently. In this article, we systemically reviewed the studies regarding the effectiveness of 2- or 3-dose vaccines delivered in either homologous or heterologous manner. The humoral and cellular immune responses elicited by various vaccine regimens to protect against Omicron variant are discussed. Current understanding of the molecular basis underlying immune escape of Omicron was also analyzed. These studies indicate that two doses of vaccination are insufficient to elicit neutralizing antibody responses against Omicron variant. Nevertheless, Omicron-specific humoral immune responses can be enhanced by booster dose of almost all type vaccines in certain degree, and heterologous vaccination strategy may represent a better choice than homogenous regimens. Intriguingly, results of studies indicate that all current vaccines are still able to elicit robust T cell response against Omicron. Future focus should be the development of Omicron variant vaccine, which may induce potent humoral as well as cellular immune responses simultaneously against all known variants of the SARS-CoV-2 virus. 相似文献