Synthesis and evaluation of 7-chloro-4-(piperazin-1-yl)quinoline-sulfonamide as hybrid antiprotozoal agents

A new series of 4-aminochloroquinoline based sulfonamides were synthesized and evaluated for antiamoebic and antimalarial activities. Out of the eleven compounds evaluated (F1–F11), two of them (F3 and F10) showed good activity against Entamoeba histolytica (IC₅₀ <5 μM). Three of the compounds (F5, F7 and F8) also displayed antimalarial activity against the chloroquine-resistant (FCR-3) strain of Plasmodium falciparum with IC₅₀ values of 2 μM. Compound F7, whose crystal structure was also determined, inhibited β-haematin formation more potently than quinine. To further understand the action of hybrid molecules F7 and F8, molecular docking was carried out against the homology model of P. falciparum enzyme dihydropteroate synthase (PfDHPS). The complexes showed that the inhibitors place themselves nicely into the active site of the enzyme and exhibit interaction energy which is in accordance with our activity profile data. Application of Lipinski ‘rule of five’ on all the compounds (F1–F11) suggested high drug likeness of F7 and F8, similar to quinine.     

Encystment of <Emphasis Type="Italic">Azotobacter nigricans</Emphasis> grown diazotrophically on kerosene as sole carbon source

Encystment of Azotobacter nigricans was induced by its diazotrophic cultivation on kerosene. Its growth and nitrogenase activity were affected by kerosene in comparison to cultures grown on sucrose. Electron microscopy of vegetative cells showed that when nitrogenase activity was higher and the poly-β-hydroxybutyrate granules were not present to a significant extent, peripheral bodies were abundant. After 8 days of culture on kerosene, the presence of cysts with intracellular bunches of poly-β-hydroxybutyrate granules was observed. Germination of cysts bears germinating multicelled yet unbroken capsule cysts with up to three cells inside. This is the first report of encystment induction of Azotobacter species grown on kerosene.     

Cesarean Section Rates and Indications in Sub-Saharan Africa: A Multi-Country Study from Medecins sans Frontieres

Objectives

The World Health Organization considers Cesarean section rates of 5–15% to be the optimal range for targeted provision of this life saving intervention. However, access to safe Cesarean section in resource-limited settings is much lower, estimated at 1–2% reported in sub-Saharan Africa. This study reports Cesarean sections rates and indications in Democratic Republic of Congo, Burundi, and Sierra Leone, and describe the main parameters associated with maternal and early neonatal mortality.

Methods

Women undergoing Cesarean section from August 1 2010 to January 31 2011 were included in this prospective study. Logistic regression was used to model determinants of maternal and early neonatal mortality.

Results

1276 women underwent a Cesarean section, giving a frequency of 6.2% (range 4.1–16.8%). The most common indications were obstructed labor (399, 31%), poor presentation (233, 18%), previous Cesarean section (184, 14%), and fetal distress (128, 10%), uterine rupture (117, 9%) and antepartum hemorrhage (101, 8%). Parity >6 (adjusted odds ratio [aOR] = 8.6, P = 0.015), uterine rupture (aOR = 20.5; P = .010), antepartum hemorrhage (aOR = 13.1; P = .045), and pre-eclampsia/eclampsia (aOR = 42.9; P = .017) were associated with maternal death. Uterine rupture (aOR = 6.6, P<0.001), anterpartum hemorrhage (aOR = 3.6, P<0.001), and cord prolapse (aOR = 2.7, P = 0.017) were associated with early neonatal death.

Conclusions

This study demonstrates that target Cesarean section rates can be achieved in sub-Saharan Africa. Identifying the common indications for Cesarean section and associations with mortality can target improvements in antenatal services and emergency obstetric care.     

HUPO 2011: The new Cardiovascular Initiative - integrating proteomics and cardiovascular biology in health and disease

A newly reorganized HUPO Cardiovascular Initiative was announced at the HUPO 2011 Cardiovascular Initiative Workshop at Geneva. The new initiative is now part of the biology- and disease-driven component of the HUPO Human Proteome Project (B/D-HPP). Here we report the recent achievements and future directions of the initiative, and offer a perspective on the present challenges of cardiovascular proteomics and its integration with the cardiovascular biology community at large.     

Evolutionary relationships can be more important than abiotic conditions in predicting the outcome of plant–plant interactions

Positive and negative plant–plant interactions are major processes shaping plant communities. They are affected by environmental conditions and evolutionary relationships among the interacting plants. However, the generality of these factors as drivers of pairwise plant interactions and their combined effects remain virtually unknown. We conducted an observational study to assess how environmental conditions (altitude, temperature, irradiance and rainfall), the dispersal mechanism of beneficiary species and evolutionary relationships affected the co‐occurrence of pairwise interactions in 11 Stipa tenacissima steppes located along an environmental gradient in Spain. We studied 197 pairwise plant–plant interactions involving the two major nurse plants (the resprouting shrub Quercus coccifera and the tussock grass S. tenacissima) found in these communities. The relative importance of the studied factors varied with the nurse species considered. None of the factors studied were good predictors of the co‐ocurrence between S. tenacissima and its neighbours. However, both the dispersal mechanism of the beneficiary species and the phylogenetic distance between interacting species were crucial factors affecting the co‐occurrence between Q. coccifera and its neighbours, while climatic conditions (irradiance) played a secondary role. Values of phylogenetic distance between 207–272.8 Myr led to competition, while values outside this range or fleshy‐fruitness in the beneficiary species led to positive interactions. The low importance of environmental conditions as a general driver of pairwise interactions was caused by the species‐specific response to changes in either rainfall or radiation. This result suggests that factors other than climatic conditions must be included in theoretical models aimed to generally predict the outcome of plant–plant interactions. Our study helps to improve current theory on plant–plant interactions and to understand how these interactions can respond to expected modifications in species composition and climate associated to ongoing global environmental change.     

Geographical variation in cloacal microflora and bacterial antibiotic resistance in a threatened avian scavenger in relation to diet and livestock farming practices

The impact on wildlife health of the increase in the use of antimicrobial agents with the intensification of livestock production remains unknown. The composition, richness and prevalence of cloacal microflora as well as bacterial resistance to antibiotics in nestlings and full-grown Egyptian vultures Neophron percnopterus were assessed in four areas of Spain in which the degree of farming intensification differs. Differences in diet composition, especially the role of stabled livestock carrion, appear to govern the similarities of bacterial flora composition among continental populations, while the insular vulture population (Fuerteventura, Canary Islands) showed differences attributed to isolation. Evidence of a positive relationship between the consumption of stabled livestock carrion and bacterial resistance to multiple antibiotics was found. Bacterial resistance was high for semisynthetic penicillins and enrofloxacin, especially in the area with the most intensive stabled livestock production. The pattern of antibiotic resistance was similar for the different bacterial species within each area. Bacterial resistance to antibiotics may be determined by resistance of bacteria present in the livestock meat remains that constituted the food of this species, as indicated by the fact that resistance to each antibiotic was correlated in Escherichia coli isolated from swine carrion and Egyptian vulture nestlings. In addition, resistance in normal faecal bacteria (present in the microflora of both livestock and vultures) was higher than in Staphylococcus epidermidis, a species indicator of the transient flora acquired presumably through the consumption of wild rabbits. Potential negative effects of the use of antimicrobials in livestock farming included the direct ingestion of these drug residues and the effects of bacterial antibiotic resistance on the health of scavengers.     

New unsymmetric dinuclear Cu(II)Cu(II) complexes and their relevance to copper(II) containing metalloenzymes and DNA cleavage

The new homodinuclear complexes, [Cu(2)(II)(HLdtb)(mu-OCH(3))](ClO(4))(2) (1) and [Cu(2)(II)(Ldtb)(mu-OCH(3))](BPh(4)) (2), with the unsymmetrical N(5)O(2) donor ligand (H(2)Ldtb) - {2-[N,N-Bis(2-pyridylmethyl)aminomethyl]-6-[N',N'-(3,5-di-tert-butylbenzyl-2-hydroxy)(2-pyridylmethyl)]aminomethyl}-4-methylphenol have been synthesized and characterized in the solid state by X-ray crystallography.In both cases the structure reveals that the complexes have a common {Cu(II)(mu-phenoxo)(mu-OCH(3))Cu(II)} structural unit.Magnetic susceptibility studies of 1 and 2 reveal J values of -38.3 cm(-1) and -2.02 cm(-1), respectively, and that the degree of antiferromagnetic coupling is strongly dependent on the coordination geometries of the copper centers within the dinuclear {Cu(II)(mu-OCH(3))(mu-phenolate)Cu(II)} structural unit.Solution studies in dichloromethane, using UV-Visible spectroscopy and electrochemistry, indicate that under these experimental conditions the first coordination spheres of the Cu(II) centers are maintained as observed in the solid state structures, and that both forms can be brought into equilibrium ([Cu(2)(HLdtb)(mu-OCH(3))](2+)=[Cu(2)(Ldtb)(mu-OCH(3))](+)+H(+)) by adjusting the pH with Et(3)N (Ldtb(2-) is the deprotonated form of the ligand).On the other hand, potentiometric titration studies of 1 in an ethanol/water mixture (70:30 V/V; I=0.1M KCl) show three titrable protons, indicating the dissociation of the bridging CH(3)O(-) group.The catecholase activity of 1 and 2 in methanol/water buffer (30:1 V/V) demonstrates that the deprotonated form is the active species in the oxidation of 3,5-di-tert-butylcatechol and that the reaction follows Michaelis-Menten behavior with k(cat)=5.33 x 10(-3)s(-1) and K(M)=3.96 x 10(-3)M. Interestingly, 2 can be electrochemically oxidized with E(1/2)=0.27 V vs.Fc(+)/Fc (Fc(+)/Fc is the redox pair ferrocinium/ferrocene), a redox potential which is believed to be related to the formation of a phenoxyl radical.Since these complexes are redox active species, we analyzed their activity toward the nucleic acid DNA, a macromolecule prone to oxidative damage.Interestingly these complexes promoted DNA cleavage following an oxygen dependent pathway.     

A new Species of <Emphasis Type="Italic">Ceratozamia</Emphasis> (Zamiaceae) from the Sierra Norte of Puebla,Mexico

Recent collections of Ceratozamia from the Sierra Norte of Puebla, Mexico, point to a new undescribed species, which was previously subsumed under the concept of C. mexicana. Identification of this new species resulted from a review of three associated species: C. mexicana, C. tenuis, and C. delucana. Here we describe Ceratozamia totonacorum and provide information regarding its distribution and natural history. The Ceratozamia species from the Sierra Madre Oriental, Mexico, are circumscribed using morphological characters, including a detailed evaluation of reproductive structures such as the apex, position, color and shape of the ovulate strobilus.     

Dormancy and germination: making every seed count in restoration

From 50 to 90% of wild plant species worldwide produce seeds that are dormant upon maturity, with specific dormancy traits driven by species' occurrence geography, growth form, and genetic factors. While dormancy is a beneficial adaptation for intact natural systems, it can limit plant recruitment in restoration scenarios because seeds may take several seasons to lose dormancy and consequently show low or erratic germination. During this time, seed predation, weed competition, soil erosion, and seed viability loss can lead to plant re‐establishment failure. Understanding and considering seed dormancy and germination traits in restoration planning are thus critical to ensuring effective seed management and seed use efficiency. There are five known dormancy classes (physiological, physical, combinational, morphological, and morphophysiological), each requiring specific cues to alleviate dormancy and enable germination. The dormancy status of a seed can be determined through a series of simple steps that account for initial seed quality and assess germination across a range of environmental conditions. In this article, we outline the steps of the dormancy classification process and the various corresponding methodologies for ex situ dormancy alleviation. We also highlight the importance of record‐keeping and reporting of seed accession information (e.g. geographic coordinates of the seed collection location, cleaning and quality information, storage conditions, and dormancy testing data) to ensure that these factors are adequately considered in restoration planning.