Inhibition of Mycobacterium tuberculosis InhA: Design,synthesis and evaluation of new di-triclosan derivatives

Multi-drug resistant tuberculosis (MDR-TB) represents a growing problem for global healthcare systems. In addition to 1.3 million deaths in 2018, the World Health Organisation reported 484,000 new cases of MDR-TB. Isoniazid is a key anti-TB drug that inhibits InhA, a crucial enzyme in the cell wall biosynthesis pathway and identical in Mycobacterium tuberculosis and M. bovis. Isoniazid is a pro-drug which requires activation by the enzyme KatG, mutations in KatG prevent activation and confer INH-resistance. ‘Direct inhibitors’ of InhA are attractive as they would circumvent the main clinically observed resistance mechanisms. A library of new 1,5-triazoles, designed to mimic the structures of both triclosan molecules uniquely bound to InhA have been synthesised. The inhibitory activity of these compounds was evaluated using isolated enzyme assays with 2 (5-chloro-2-(4-(5-(((4-(4-chloro-2-hydroxyphenoxy)benzyl)oxy)methyl)-1H-1,2,3-triazol-1-yl)phenoxy)phenol) exhibiting an IC₅₀ of 5.6 µM. Whole-cell evaluation was also performed, with 11 (5-chloro-2-(4-(5-(((4-(cyclopropylmethoxy)benzyl)oxy)methyl)-1H-1,2,3-triazol-1-yl)phenoxy)phenol) showing the greatest potency, with an MIC₉₉ of 12.9 µM against M. bovis.     

Being human: Why and in what sense it is morally relevant

The debate on the question of the moral status of human beings and the boundaries of the moral community has long been dominated by the antagonism between personism and speciesism: either certain mental properties or membership of the human species is considered morally crucial. In this article, I argue that both schools of thought are equally implausible in major respects, and that these shortcomings arise from the same reason in both cases: a biological notion of being human. By contrast, I show to what extent being human is morally relevant in a non-biological sense. I establish the living human form as the essential criterion for belonging to the moral community, and defend it against a number of possible objections. This new morphological approach is capable of capturing essential elements of personism and speciesism without sharing their faults, and of reconstructing widespread moral intuitions.     

Oxalate Accumulation as Regulated by Nitrogen Forms and Its Relationship to Photosynthesis in Rice （Oryza sativa L.）

Four-leaf rice seedlings (Oryza sativa L.), which had been cultivated in Kimura B complete nutrient solution, were treated with two nitrogen forms by replacing the nitrogen element in the complete solution with sole nitrate or ammonium (2.86 mmol/L). Nitrate-N nutrition tended to increase oxalate content in all parts of the plant, including the leaves, stems, roots, and root exudates, whereas ammonium had the opposite effect. Consequently, marked differences in oxalate content were observed between the two treatments throughout the time tested (0-12 d), with maximal differences of approximately 12-fold at 6d after treatment. Photosynthetic/respiratory parameters were examined over time simultaneously with changes in oxalate content. Net photosynthetic rate, chlorophyll fluorescence parameters (i.e. maximal photochemical efficiency (Fv/Fm) and photochemical quantum yields of photosystem (PS)II (ΦPSⅡ)), and respiratory rate were not significantly different between plants treated with the two nitrogen forms, although ammonium-fed plants had apparently higher leaf chlorophyll content than nitrate-fed plants. Leaf glucose content was altered little, but the content of fructose, sucrose, and total soluble sugar was significantly higher in the leaves of ammonium-fed plants than nitrate-fed plants. The results indicate that nitrate/ammonium may serve as efficient regulators of oxalate accumulation owing to regulation of metabolism in rice leaves rather than oxalate downward transfer and root excretion, and that photosynthetic metabolism is not directly correlated with the regulation of oxalate accumulation in rice plants.     

Properties of Antigenomic HDV Ribozyme Consisting of Two RNA Chains

B:LS ribozyme, a trans-variant of naturally occurring HDV ribozyme, has been constructed. The ribozyme consists of a substrate-containing LS chain and a catalytic B chain and differs from previously constructed trans-ribozymes in the length and nucleotide sequence of its oligonucleotide chains (33 and 34 bp, respectively). The chains readily associate with each other at room temperature, at which the LS cleavage reaction is negligible, which makes it possible to investigate association of the intact chains. At the same time, the self-cleavage rate constant for the trans-ribozyme B:LS at 50°C is close to those for the previously studied permuted cis-ribozymes, especially the LSB variant. In addition, the dependence of trans-ribozyme on reaction conditions (Mg²⁺ concentration, pH, and temperature) resembled that of cis-ribozyme. Similar to other trans-ribozymes, B:LS ribozyme demonstrated the ability for multiple turnover of the B strand with an excess of the substrate LS chain. The kinetic model of the self-cleavage reaction for B:LS is presented at http://www.cardio.ru/labgen/RZ_r.html. Taken together, our results show that the novel trans-variant of HDV ribozyme can be used as a model for analyzing the process of HDV ribozyme self-cleavage.     

Does Neighborhood Floral Display Matter? Fruit Set in Carpenter Bee‐pollinated Heterophragma quadriloculare and Beetle‐pollinated Lasiosiphon eriocephalus

Fruit set is pollen‐limited in the self‐incompatible tree Heterophragma quadriloculare (Bignoniaceae), pollinated by long‐distance flying carpenter bees, and in the self‐compatible shrub Lasiosiphon eriocephalus (Thymdeaceae), pollinated by weak‐flying, sedentary beetles. We studied a single H. quadriloculare population over high and low flowering years and found no difference in bee visitation rates between these years. For H. quadriloculare, neighborhood floral display did not make a significant contribution to reproductive success. We investigated dense and sparse L. eriocephalus populations in the same year. In the low density L. eriocephalus population, individual floral displays were higher than in the dense population, yet reproductive success was low, indicating that plant isolation was a major factor influencing fruit set. This result was due to the extremely low number of beetles per plant and per flower in this population. In the dense L. eriocephalus population, although the displays of individual neighbors were smaller and plants were closer, neighborhood floral display did not contribute significantly to reproductive success, whereas the effect of individual floral display was ambiguous. Species with self‐incompatible rather than self‐compatible breeding systems are expected to experience neighborhood effects on reproductive success; however, at the spatial scale and floral display levels of plants in this study, only individual floral display affected fruit set in H. quadriloculare, whereas neither individual nor neighborhood display influenced fruit set in L. eriocephalus. Therefore, pollinator type, pollinator behavior, and plant and population isolation, rather than breeding system alone, will determine if neighborhood floral display affects fruit set.     

内蒙古、宁夏维管植物新资料

报道了宁夏地区3个新分布记录种--卵叶铁角蕨、野青茅、藏芨芨草和内蒙古地区青兰属(唇形科)一新变型--白花香青兰,该新变型花冠白色,明显不同于原变型的蓝紫色花冠.     

Mechanism and regulation of the violaxanthin cycle: The role of antenna proteins and membrane lipids

The violaxanthin cycle describes the reversible conversion of violaxanthin to zeaxanthin via the intermediate antheraxanthin. This light-dependent xanthophyll conversion is essential for the adaptation of plants and algae to different light conditions and allows a reversible switch of photosynthetic light-harvesting complexes between a light-harvesting state under low light and a dissipative state under high light. The photoprotective functions of zeaxanthin have been intensively studied during the last decade, but much less attention has been directed to the mechanism and regulation of xanthophyll conversion. In this review, an overview is given on recent progress in the understanding of the role of (i) xanthophyll binding by antenna proteins and of (ii) the lipid properties of the thylakoid membrane in the regulation of xanthophyll conversion. The consequences of these findings for the mechanism and regulation of xanthophyll conversion in the thylakoid membrane will be discussed.     

Development and Growth Form of the Neotropical Liana <Emphasis Type="Italic">Croton nuntians</Emphasis>: The Effect of Light and Mode of Attachment on the Biomechanics of the Stem

The neotropical liana Croton nuntians (Euphorbiaceae) can occur in a variety of different growth habits. Juvenile freestanding plants are mechanically stable without support and resemble morphologically young trees or shrubs, whereas adult plants are climbers. Ontogenetic variation of bending and torsion properties of different growth phases are analyzed by measurements of flexural stiffness, structural bending modulus, torsional stiffness and structural torsional modulus. Mechanical and anatomical data show two fundamentally different patterns for juvenile freestanding and adult climbing plants. In freestanding plants, mechanical properties and the contribution of cortex, wood, and pith to the stem cross-section vary only little during ontogeny as is typical for semi-self-supporting plants. In contrast, climbing plants become significantly more flexible during ontogeny, as is characteristic for lianas. This is accompanied by a transition to the formation of a less dense wood type with large diameter vessels and an increasing contribution of flexible tissues (less dense wood and cortex) to the cross-sectional area and the axial second moment of area of the stems. Depending on the environmental conditions, freestanding plants can differ considerably in their appearance due to differences in branching system or stem taper. Therefore the influence of light quantity, measured as percentage of canopy opening, on the mechanical properties and the stem anatomy was tested. Freestanding plants grown with strong shade are significantly more stiff in bending compared with plants grown with a moderate light environment.     

Looks matter: changes in flower form affect pollination effectiveness in a sexually deceptive orchid

Many species of the sexually deceptive genus Ophrys are characterized by insect‐like flowers. Their form has been traditionally considered to play an important role in pollinator attraction and manipulation. Yet, the evolution of the floral form remains insufficiently understood. We hypothesize that pollinator‐mediated selection is essential for driving floral form evolution in Ophrys, but that form components are being subjected to varying selection pressures depending on their role in mediating interactions with pollinators. By using the Eucera‐pollinated Ophrys leochroma as a model, our aim has been to assess whether and in what manner pollination effectiveness is altered by experimental manipulation of the flower form. Our results show that floral form plays an essential and, so far, underestimated role in ensuring effective pollination by mechanically guiding pollinators towards the reproductive structures of the flower. Pollinators are significantly less effective in interacting with flowers having forms altered to resemble those of species pollinated by different hymenopteran genera. Further, those components used by pollinators as gripping points were found to be more effective in ensuring pollinia transfer than those with which pollinators do not directly interact. Thus, mechanically active and inactive components appear to be under different selection pressures. As a consequence, mechanically active components of the flower form could reflect adaptations to the interaction with particular pollinator groups, whereas mechanically inactive components can vary more freely. Disentangling selection patterns between the functionally different components of flower form may provide valuable insights into the mechanisms driving the morphological diversification of sexually deceptive pollination systems.     

Concentrations and chemical forms of heavy metals in agricultural soil near the world’s largest and oldest tungsten mine located in China

Abstract

Tungsten (W) mining has taken place in Ganzhou in China for about 100 years. Such long-term W mining may release large amount of metals to soils and waters around these mines. Twenty soil samples were taken from the area around the W mines and 10 soil samples from an area much farther away. These soil samples were analysed for physicochemical properties, heavy metal content and their chemical forms. Results show that long-term W mining significantly increased both total and labile contents of Cd, Cu, Pb and Zn, but did not, or only slightly, increased the total content of Co, Cr and Ni in the soil near the mine. Average enrichment factor (EF) in the agricultural soils was 4.0, 2.4, 2.2, and 2.0 for Cd, Cu, Pb and Zn, respectively. The labile fraction was dominated by the carbonate-bound fraction for Cd (54.5%) and organic matter-bound fraction for Cu (37.9%), while the major labile fractions for Pb and Zn were associated with carbonates (30.2% and 6.4%), oxides (17.9% and 10.6%) and organic matter (9.2% and 18.8%). Consequently, there is a need to be cautious about Cd in the soils contaminated by W mining.