Linking oxidative and salinity stress tolerance in barley: can root antioxidant enzyme activity be used as a measure of stress tolerance?

Aims

A causal relationship between salinity and oxidative stress tolerance and a suitability of using root antioxidant activity as a biochemical marker for salinity tolerance in barley was investigated.

Methods

Net ion fluxes were measured from the mature zone of excised roots of two barley varieties contrasting in their salinity tolerance using non-invasive MIFE technique in response to acute and prolonged salinity treatment. These changes were correlated with activity of major antioxidant enzymes; ascorbate peroxidase, catalase, and superoxide dismutase.

Results

It was found that genotypic difference in salinity tolerance was largely independent of root integrity, and observed not only for short-term but also long-term NaCl exposures. Higher K⁺ retention ability (and, hence, salinity tolerance) positively correlated with oxidative stress tolerance. At the same time, antioxidant activities were constitutively higher in a sensitive but not tolerant variety, and no correlation was found between SOD activity and salinity tolerance index during large-scale screening.

Conclusion

Although salinity tolerance in barley correlates with its oxidative stress tolerance, higher antioxidant activity at one particular time does not correlate with salinity tolerance and, as such, cannot be used as a biochemical marker in barley screening programs.     

How can natural products serve as a viable source of lead compounds for the development of new/novel anti-malarials?

Background

Change of Kenyan treatment policy for uncomplicated malaria from sulphadoxine-pyrimethamine to artemether-lumefantrine (AL) was accompanied by revised recommendations promoting presumptive malaria diagnosis in young children and, wherever possible, parasitological diagnosis and adherence to test results in older children and adults. Three years after the policy implementation, health workers' adherence to malaria diagnosis and treatment recommendations was evaluated.

Methods

A national cross-sectional, cluster sample survey was undertaken at public health facilities. Data were collected using quality-of-care assessment methods. Analysis was restricted to facilities with AL in stock. Main outcomes were diagnosis and treatment practices for febrile outpatients stratified by age, availability of diagnostics, use of malaria diagnostic tests, and test result.

Results

The analysis included 1,096 febrile patients (567 aged <5 years and 529 aged ≥5 years) at 88 facilities with malaria diagnostics, and 880 febrile patients (407 aged <5 years and 473 aged ≥5 years) at 71 facilities without malaria diagnostic capacity. At all facilities, 19.8% of young children and 28.7% of patients aged ≥5 years were tested, while at facilities with diagnostics, 33.5% and 53.7% were respectively tested in each age group. Overall, AL was prescribed for 63.6% of children aged <5 years and for 65.0% of patients aged ≥5 years, while amodiaquine or sulphadoxine-pyrimethamine monotherapies were prescribed for only 2.0% of children and 3.9% of older children and adults. In children aged <5 years, AL was prescribed for 74.7% of test positive, 40.4% of test negative and 60.7% of patients without test performed. In patients aged ≥5 years, AL was prescribed for 86.7% of test positive, 32.8% of test negative and 58.0% of patients without test performed. At least one anti-malarial treatment was prescribed for 56.6% of children and 50.4% of patients aged ≥5 years with a negative test result.

Conclusions

Overall, malaria testing rates were low and, despite different age-specific recommendations, only moderate differences in testing rates between the two age groups were observed at facilities with available diagnostics. In both age groups, AL use prevailed, and prior ineffective anti-malarial treatments were nearly non-existent. The large majority of test positive patients were treated with recommended AL; however, anti-malarial treatments for test negative patients were widespread, with AL being the dominant choice. Recent change of diagnostic policy to universal testing in Kenya is an opportunity to improve upon the quality of malaria case management. This will be, however, dependent upon the delivery of a comprehensive case management package including large scale deployment of diagnostics, good quality of training, post-training follow-up, structured supervisory visits, and more intense monitoring.     

How can natural products serve as a viable source of lead compounds for the development of new/novel anti-malarials?

Malaria continues to be an enormous global health challenge, with millions of new infections and deaths reported annually. This is partly due to the development of resistance by the malaria parasite to the majority of established anti-malarial drugs, a situation that continues to hamper attempts at controlling the disease. This has spurred intensive drug discovery endeavours geared towards identifying novel, highly active anti-malarial drugs, and the identification of quality leads from natural sources would greatly augment these efforts. The current reality is that other than compounds that have their foundation in historic natural products, there are no other compounds in drug discovery as part of lead optimization projects and preclinical development or further that have originated from a natural product start-point in recent years. This paper briefly presents both classical as well as some more modern, but underutilized, approaches that have been applied outside the field of malaria, and which could be considered in enhancing the potential of natural products to provide or inspire the development of anti-malarial lead compounds.     

Peel of araticum fruit (Annona crassiflora Mart.) as a source of antioxidant compounds with α-amylase, α-glucosidase and glycation inhibitory activities

Annona crassiflora Mart., whose fruit is popularly known as araticum, is a member of the Annonaceae family found in the Brazilian Cerrado. Although this plant has several medicinal uses, its bioactive molecules are not fully understood. A bioguided assay was performed to identify the main bioactive compounds of A. crassiflora fruit peel from the ethanol extract fractions with antioxidant capacity and α-amylase, α-glucosidase and glycation inhibitory activities. Ethyl acetate and n-butanol fractions showed, respectively, higher antioxidant capacity (DPPH IC₅₀ 1.5 ± 0.1 and 0.8 ± 0.1 μg mL⁻¹, ORAC 3355 ± 164 and 2714 ± 79 μmol trolox eq/g, and FRAP 888 ± 16 and 921 ± 9 μmol trolox eq/g) and inhibitory activities against α-amylase (IC₅₀ 4.5 ± 0.8 and 1.7 ± 0.3 μg mL⁻¹), α-glucosidase (IC₅₀ 554.5 ± 158.6 and 787.8 ± 140.6 μg mL⁻¹) and glycation (IC₅₀ 14.3 ± 3.3 and 16.0 ± 4.2 μg mL⁻¹), and lower cytotoxicity, compared to the other fractions and crude ethanol extract. The HPLC-ESI-MS/MS analysis identified various biomolecules known as potent antioxidants, such as chlorogenic acid, (epi)catechin, procyanidins, caffeoyl-hexosides, quercetin-glucosides and kaempferol. The fruit peel of A. crassiflora, a specie from Cerrado, the Brazilian Savanna, provided a source of antioxidant compounds with properties to block carbohydrate digestive enzymes and formation of glycation products. Thus, there is potential to use the by-products of araticum in order to identify and isolate phytochemicals for application in nutraceutical supplements, food additives and pharmaceuticals products.     

Turkey intestine as a commercial source of heparin? Comparative structural studies of intestinal avian and mammalian glycosaminoglycans

Heparin is a glycosaminoglycan (GAG) that is extracted primarily from porcine intestinal tissues and is widely used as a clinical anticoagulant. It is biosynthesized as a proteoglycan and stored exclusively in mast cells and is partially degraded to peptidoglycan and GAG on immunologically activated mast cell degranulation. In contrast, the structurally related heparan sulfate, is the polysaccharide portion of a ubiquitous proteoglycan, localized on cell surface and in the extracellular matrix of all animal tissues. Heparin and heparan sulfate are made in the Golgi through a similar biosynthetic pathway. The current study was undertaken in a search for alternative, non-mammalian, sources of anticoagulant heparin. The heparin/heparan sulfate family of GAGs, prepared and purified from turkey intestine, were assayed for anticoagulant activity and structurally characterized. The resulting GAGs displayed a very low anticoagulant activity when compared to those obtained from porcine intestine using an identical procedure. Structural characterization studies clearly demonstrate that heparan sulfate is the major GAG in the turkey intestine. This observation is rationalized based on differences in the mammalian and avian coagulation and immune systems.     

A new lignan and a new alkaloid,and α-glucosidase inhibitory compounds from the grains of Echinochloa utilis Ohwi & Yabuno

A new lignan, utilisin (1), and a new alkaloid, echinoutilin (2), together with eleven known compounds 3–13 were isolated from the grains of Echinochloa utilis Ohwi & Yabuno. Their structures were identified through the analysis of spectroscopic data. The absolute configuration of 2 was determined by Mosher’s method. These compounds were evaluated for α-glucosidase inhibitory activity. Among them, compounds 2, 3 and 6 exhibited considerable α-glucosidase inhibitory activity with IC₅₀ values of 42.1 ± 1.3, 58.9 ± 3.7, and 40.9 ± 1.1 μM, respectively. The results indicate that the grains of E. utilis will be useful in the treatment of diabetes control agents.     

Hairy root cultures of Taxus × media var. Hicksii Rehd. as a new source of paclitaxel and 10-deacetylbaccatin III

Hairy root cultures of Taxus × media var. Hicksii were established by infection of the plantlets with the Agrobacterium rhizogenes strain LBA 9402. The paclitaxel accumulation in hairy root cultures increased after 100 M methyl jasmonate treatment from 69 to 210 g g^–1 dry wt while the 10-deacetybaccatin III content was not affected by the elicitor.     

Novel oxazolxanthone derivatives as a new type of α-glucosidase inhibitor: synthesis,activities, inhibitory modes and synergetic effect

Xanthone derivatives have shown good α-glucosidase inhibitory activity and have drawn increased attention as potential anti-diabetic compounds. In this study, a series of novel oxazolxanthones were designed, synthesized, and investigated as α-glucosidase inhibitors. Inhibition assays indicated that compounds 4–21 bearing oxazole rings exhibited up to 30-fold greater inhibitory activity compared to their corresponding parent compound 1b. Among them, compounds 5–21 (IC₅₀?=?6.3?±?0.4–38.5?±?4.6?μM) were more active than 1-deoxynojirimycin (IC₅₀?=?60.2?±?6.2?μM), a well-known α-glucosidase inhibitor. In addition, the kinetics of enzyme inhibition measured by using Lineweaver–Burk analysis shows that compound 4 is a competitive inhibitor, while compounds 15, 16 and 20 are non-competitive inhibitors. Molecular docking studies showed that compound 4 bound to the active site pocket of the enzyme while compounds 15, 16, and 20 did not. More interestingly, docking simulations reveal that some of the oxazolxanthone derivatives bind to different sites in the enzyme. This prediction was further confirmed by the synergetic inhibition experiment, and the combination of representative compounds 16 and 20 at the optimal ratio of 4:6 led to an IC₅₀ value of 1.9?±?0.7?μM, better than the IC₅₀ value of 7.1?±?0.9?μM for compound 16 and 8.6?±?0.9?μM for compound 20.     

A new insight into the oxidative mechanism of caffeine and related methylxanthines in aprotic medium: May caffeine be really considered as an antioxidant?

Background

Antioxidant properties have been recently suggested for caffeine that seems showing protective effects against damages caused by oxidative stress. In particular, a HO scavenging activity has been ascribed to caffeine. Even if the oxidation of caffeine has been widely studied, the antioxidant mechanism is still far to be understood.

The Enemy as a Patient: What can be Learned from the Emotional Experience of Physicians and Why does it Matter Ethically?

This qualitative research examines the influence of animosity on physicians during clinical encounters and its ethical implications. Semi‐structured interviews were conducted with ten Israeli‐Jewish physicians: four treated Syrians and six treated Palestinian terrorists/Hezbollah militants or Palestinian civilians. An interpretive phenomenological analysis was used to uncover main themes in these interviews. Whereas the majority of physicians stated they are obligated to treat any patient, physicians who treated Syrians exhibited stronger emotional expression and implicit empathy, while less referring to the presence of the Israeli‐Arab conflict. In contrast, physicians who treated enemy combatants or Palestinian civilians showed the exact opposite. Linking these results to the “Implicit Bias” theory, the role of empathy and the beneficence principle in medical ethics, we argue that: (a) the unconscious decreased emotional involvement among the latter group of physicians is a deficiency that needs to be recognized; and (b) this deficiency undermines the principle of beneficence, thereby possibly influencing the fulfillment of the commitment to treat patients. Acknowledging and addressing the potential emotional and ethical deficiencies entailed in encounters with the so‐called enemy‐patients are of importance to the global medical community, since such encounters are increasingly an integral part of the current political realities faced by both the developed and developing worlds.     

δ1-Pyrroline-5-carboxylate reductase as a new target for therapeutics: inhibition of the enzyme from Streptococcus pyogenes and effects in vivo

Compounds able to interfere with amino acid biosynthesis have the potential to inhibit cell growth. In both prokaryotic and eukaryotic microorganisms, unless an ornithine cyclodeaminase is present, the activity of δ¹-pyrroline-5-carboxylate (P5C) reductase is mandatory to proline production, and the enzyme inhibition should result in amino acid starvation, blocking in turn protein synthesis. The ability of some substituted derivatives of aminomethylenebisphosphonic acid and its analogues to interfere with the activity of the enzyme from the human pathogen Streptococcus pyogenes was investigated. Several compounds were able to suppress activity in the micromolar range of concentrations, with a mechanism of uncompetitive type with respect to the substrate P5C and non-competitive with respect to the electron donor NAD(P)H. The actual occurrence of enzyme inhibition in vivo was supported by the effects of the most active derivatives upon bacterial growth and free amino acid content.     

A new genus and eight new species of the subtribe Anillina (Carabidae,Trechinae, Bembidiini) from Mexico,with a cladistic analysis and some notes on?the?evolution of the genus

One new genus and eight new species of anilline carabids are described from southern Mexico. The new genus, Zapotecanillus gen. n., is established for Z. oaxacanus (type species) sp. n., Z. nanus sp. n., Z. iviei sp. n., Z. ixtlanus sp. n., Z. montanus sp. n., and Z. kavanaughi sp. n. from the Sierra Madre de Oaxaca, Z. pecki sp. n. from the Sierra Madre del Sur, and Z. longinoi sp. n. from the Sierra Madre de Chiapas. A taxonomic key for all described species of Zapotecanillus and a cladistic analysis, based on morphological data, are provided. Morphological, behavioral and biogeographical aspects of the speciation in the genus obtained from the resulting cladogram are discussed.     

Should Bromus secalinus (rye brome) be considered a crop?: Analysis of Bromus rich assemblages from protohistoric and historic sites in northern France and textual references

Vegetation History and Archaeobotany - Several hundred archaeobotanical studies now provide a broad overview of plant husbandry practices in northern France from the Bronze Age to the medieval...     

Can land crabs be used as a rapid ecosystem evaluation tool? A test using distribution and abundance of several genera from the Seychelles

Habitat destruction and the introduction of exotic species are the primary causes of biodiversity loss in tropical island ecosystems. Conservation efforts on oceanic islands are often biased towards charismatic vertebrate faunas, neglecting invertebrate assemblages. We sampled the land crab community on five islands in the central Seychelles; in the intertidal zone, in the supralittoral zone and in nine different inland habitat types to explore the impacts of exotic vegetation and environmental variables on land crab abundance and community composition, and investigate whether land crabs can be used as a tool for the rapid assessment of habitat quality on tropical oceanic islands. We found that species richness and the abundance of the dominant ghost crab Ocypode cordimana was higher in native habitat types than habitats dominated by exotic vegetation. Available ground substrate suitable for burrowing may be a limiting factor for O. cordimana in exotic habitat types. Coenobita rugosus, the dominant crab in the supralittoral zone is largely absent where there is no supralittoral vegetation. These results suggest that land crabs could be reliable indicators of habitat quality on oceanic islands. The abundance of land crabs could be used in the rapid assessment of ecosystem perturbation and identification of sites requiring restoration or management.     

Can oxidative DNA damage be used as a biomarker of cancer risk in humans? Problems, resolutions and preliminary results from nutritional supplementation studies

Damage to DNA by oxygen radicals and other reactive oxygen/nitrogen/chlorine species occurs in vivo despite the presence of multiple antioxidant defence and repair systems. Such damage is thought to make a significant contribution to the age-related development of cancer. Modulation of oxidative DNA damage by diet thus constitutes a "biomarker" putatively predictive of the effect of diet on cancer incidence, provided that DNA damage can be accurately quantitated by validated methods. Current issues addressed in this article include the problems of artifactual DNA oxidation during isolation and analysis, the relative merits of different analytical methods, the advantages and disadvantages of relying on measurement of 8-hydroxydeoxyguanosine (8OHdG, 8-oxodG) as an index of oxidative DNA damage, and the limited data that are so far available on how diet can affect "steady-state" levels of oxidative DNA damage in humans. It appears that such damage can be modulated by vegetable intake, although the effects of vegetables may be mediated by components different from the "classical" antioxidants vitamin C, alpha-tocopherol and beta-carotene.     

FaGT2: a multifunctional enzyme from strawberry (<Emphasis Type="Italic">Fragaria</Emphasis> × <Emphasis Type="Italic">ananassa</Emphasis>) fruits involved in the metabolism of natural and xenobiotic compounds

Fragaria × ananassa UDP-glucose:cinnamate glucosyltransferase (FaGT2) catalyzes the formation of cinnamic acid and p-coumaric acid glucose esters during strawberry fruit ripening. Here, the ripening and oxidative stress induced enzyme was further characterized by testing a range of structurally different substrates of natural and unnatural origin in vitro and comparing their kinetic parameters to elucidate its additional biological functions. The accepted substrates ranged from derivatives of cinnamic acid and benzoic acid to heterocyclic and aliphatic compounds resulting in the formation of O- and S-glucose esters, as well as O-glucosides. In planta assays confirmed the formation of glucose derivatives after injection of the substrates into strawberry fruits. Common chemical and structural features required for activity were the easy subtraction of a proton from the glucosylation site and the conjugation of the formed anion with π-electrons as best realized in the simplest substrate sorbic acid. In addition to cinnamic acid, the natural compounds anthranilic acid, trans-2-hexenoic acid, nicotinic acid and 2,5-dimethyl-4-hydroxy-3[2H]-furanone were glucosylated in vitro. But FaGT2 was also capable of efficiently converting xenobiotic substances like the herbicide 2,4,5-trichlorophenol and the herbicide analogue 3,5-dichloro-4-hydroxybenzoic acid. The results suggest that FaGT2 is involved in the detoxification of xenobiotics in accordance to its induction by oxidative stress. GenBank Accession number of FaGT2: AY663785.     

Did the historical range of the European bison (<Emphasis Type="Italic">Bison bonasus</Emphasis> L.) extend further south?—a new finding from the Yenikapı Metro and Marmaray excavation,Turkey

The origin of the European bison (Bison bonasus, Linnaeus, 1758) has been widely discussed and investigated in recent years. The species had a wide historic geographic distribution throughout the European continent during the middle and late Holocene, ranging from France in the west to the Caucasus in the east. However, archaeological evidence is needed to resolve the southern extent of the European bison distribution. We discovered one bison skull fragment during archaeological excavations in 2008 in the area of Yenikap? Metro and Marmaray (Turkey). Radiocarbon dating indicated the skull was deposited during the Byzantine period (seventh to eighth century AD). Mitochondrial genome analyses provided clear evidence that the skull was from a European bison. This is the first unambiguous evidence of the presence of this species in southeastern Europe during Byzantine times, which validates the historical written records of a potentially wider range of the European bison in historical times.