Light intensity determines the extent of mercury toxicity in the cyanobacterium Nostoc muscorum

The extent of mercury (Hg) toxicity in the heterocystous cyanobacterium Nostoc muscorum grown for 72 h in three different light intensities was tested for various physiological parameters viz. growth, pigment contents, photosynthesis, respiration, reactive oxygen species (ROS), malondialdehyde formation and antioxidants. A general reduction in growth and pigments, whole cell O₂-evolution, photosynthetic electron transport activities and ¹⁴CO₂-fixation was observed in a metal concentration–dependent manner, and this effect was more pronounced in high light (130 μmol photon m⁻² s⁻¹)–exposed cells as compared to low (10 μmol photon m⁻² s⁻¹) and normal (70 μmol photon m⁻² s⁻¹) light intensity–exposed cells; however, carotenoids and respiration showed reverse trend. Among photosynthetic electron transport activities, whole chain activity was found to be most sensitive in comparison with photosystem II (PS II) and photosystem I (PS I). Comparing the different photosynthetic processes, ¹⁴CO₂-fixation was most affected in cyanobacterial cells when exposed to Hg and different light intensities. After application of various exogenous electron donors, diphenyl carbazide was found to be more effective to restore PS II activity, suggesting that site of damage lies in between oxygen evolving complex and PS II. Level of oxidative stress (superoxide radical and lipid peroxidation) was maximum at 3.0 μM of Hg when coupled with high light intensity (except hydrogen peroxide). A dose-dependent increase in enzymatic antioxidants such as superoxide dismutase, peroxidase and catalase as well as non-enzymatic antioxidants such as proline, ascorbate, cysteine (except under high light intensity) and non-protein thiols [NP-SH] was observed, which further increased with the increase in light intensity. It was noticed that Hg intoxicates N. muscorum through ROS production, which is aggravated along with the increase in light intensity. Overall results suggest that the severity of the metal stress does increase with Hg concentrations but when coupled with light, it was the light intensity that determines the extent of Hg toxicity.     

Synthesis, characterization and applications of graft copolymer (κ-carrageenan-g-vinylsulfonic acid)

The synthesis of graft copolymer (κ-carrageenan-g-vinylsulfonic acid) is carried out in nitrogen atmosphere using potassium peroxymonosulfate (PMS) and malonic acid (MA) as redox system. The effect of reaction variables including the concentration of vinylsulfonic acid 1.3×10(-2) to 6.7×10(-2) mol dm(-3), PMS 4×10(-3) to 20×10(-3) mol dm(-3), MA 1.6×10(-3) to 4.8×10(-3) mol dm(-3), sulfuric acid 1×10(-3) to 8×10(-3) mol dm(-3), κ-carrageenan 0.4-1.8 g dm(-3) as well as time duration 60-180 min and temperature 25-45 °C has been studied. The water swelling capacity of graft copolymer is investigated. Flocculation property for both coking and non-coking coals is studied for the treatment of coal mine waste water. The graft copolymer has been characterized by FTIR and thermogravimetric analysis.     

High Light Intensity Augments Mercury Toxicity in Cyanobacterium Nostoc muscorum

The present study is aimed at investigating the role of growth irradiance in determining the extent of mercury (Hg) toxicity on various physiological parameters viz. growth, pigment contents, photosynthesis, respiration, ¹⁴CO₂ fixation, photosynthetic electron transport, photorespiration and enzyme activity of cyanobacterium Nostoc muscorum. A general decline was observed in all these parameters with increasing concentration of Hg except for carotenoids content and respiratory activity which exhibited significant enhancement. This effect was more pronounced in high light (130???mol photon m^?2?s^?1) exposed cells as compared to normal (70???mol photon m^?2?s^?1) and low (10???mol photon m^?2?s^?1) light exposed cells. Among the photosynthetic electron transport activities, whole chain was found to be more sensitive than photosystem II (PSII) and photosystem I (PSI). ¹⁴CO₂ fixation was more affected as compared to O₂ evolution when exposed to Hg and different light intensities. Photorespiratory activity, which is an index of protecting organisms from light-induced damage, also showed a similar declining trend. Enzyme assay revealed that among the carboxylating enzymes, activity of RUBISCO was more severely inhibited than PEPCase. Thus, these results suggest that Hg itself was toxic at all tested concentrations and high light intensity augmented its toxicity in N. muscorum inhibiting the growth, pigment contents and photosynthetic activity of the organism.     

Hypotheses generation as supervised link discovery with automated class labeling on large-scale biomedical concept networks

Computational approaches to generate hypotheses from biomedical literature have been studied intensively in recent years. Nevertheless, it still remains a challenge to automatically discover novel, cross-silo biomedical hypotheses from large-scale literature repositories. In order to address this challenge, we first model a biomedical literature repository as a comprehensive network of biomedical concepts and formulate hypotheses generation as a process of link discovery on the concept network. We extract the relevant information from the biomedical literature corpus and generate a concept network and concept-author map on a cluster using Map-Reduce frame-work. We extract a set of heterogeneous features such as random walk based features, neighborhood features and common author features. The potential number of links to consider for the possibility of link discovery is large in our concept network and to address the scalability problem, the features from a concept network are extracted using a cluster with Map-Reduce framework. We further model link discovery as a classification problem carried out on a training data set automatically extracted from two network snapshots taken in two consecutive time duration. A set of heterogeneous features, which cover both topological and semantic features derived from the concept network, have been studied with respect to their impacts on the accuracy of the proposed supervised link discovery process. A case study of hypotheses generation based on the proposed method has been presented in the paper.     

CD14, CD16 and HLA-DR reliably identifies human monocytes and their subsets in the context of pathologically reduced HLA-DR expression by CD14(hi) /CD16(neg) monocytes: Expansion of CD14(hi) /CD16(pos) and contraction of CD14(lo) /CD16(pos) monocytes in acute liver failure

Changes in monocytes and their subsets (CD14(hi) /CD16(neg) , CD14(hi) /CD16(pos) and CD14(lo) /CD16(pos) ) have been described in several diseases. The combination of CD14, CD16 and HLA-DR has been suggested to discriminate monocytes from the CD16(pos) /HLA-DR(neg) NK-cells and neutrophils but no data exist whether this strategy can be used in situations when monocyte HLA-DR expression is pathologically reduced. Monocytes and their subsets were concurrently identified through negative (exclusion of CD66b(pos) neutrophils, CD56(pos) NKcells, CD19(pos) B-cells, and CD3(pos) T-cells) and positive gating (inclusion of monocytes by expression of CD14, CD16, and HLA-DR) strategies on 30 occasions [9 healthy controls (HC) and 21 patients with conditions associated with low monocyte HLA-DR expression]. Bland-Altman and Passing and Bablok regression statistics did not demonstrate any significant measurement bias between the two strategies of monocyte identification. Monocyte subset phenotype was then compared in 18 HC and 41 patients with acute liver failure (ALF). Compared with HC, in ALF, the percentage of CD14(hi) /CD16(pos) monocytes was higher (7% vs 4%) whilst the percentage of CD14(lo) /CD16(pos) was lower (1.9% vs. 7%) (P ≤ 0.001); HLA-DR and CD86 MFIs on all monocyte subsets were lower, whilst CCR5, CD64, and CD11b MFIs were higher (P < 0.05). The relative expression by monocyte subsets of HLA-DR, CCR2, CCR5, CX3CR1, and CD11a was similar in ALF patients and HCs. Repeat analysis of an identical antibody-fluorochrome "backbone" targeting HLA-DR, CD14, and CD16 was assessed in 189 samples across 5 different experiments. There was excellent agreement in the results obtained using the positive gating strategy (interclass correlation coefficients > 0.8). Monocytes and their subsets can be reliably identified using an antibody-fluorochrome "backbone" of HLA-DR, CD14, and CD16. CD16(pos) monocytes continue to constitutively express HLA-DR even in conditions where HLA-DR is pathologically reduced on CD14(hi) /CD16(neg) monocytes. Understanding the changes in monocyte pheontype in ALF and similar clinico-pathological diseases may allow the development of novel biomarkers or therapeutic strategies. ? 2012 International Society for Advancement of Cytometry.     

Inhibition of mycolic acid transport across the Mycobacterium tuberculosis plasma membrane

New chemotherapeutics active against multidrug-resistant Mycobacterium tuberculosis are urgently needed. We report on the identification of an adamantyl urea compound that shows potent bactericidal activity against M. tuberculosis and a unique mode of action, namely the abolition of the translocation of mycolic acids from the cytoplasm, where they are synthesized to the periplasmic side of the plasma membrane and are in turn transferred onto cell wall arabinogalactan or used in the formation of virulence-associated, outer membrane, trehalose-containing glycolipids. Whole-genome sequencing of spontaneous-resistant mutants of M. tuberculosis selected in vitro followed by genetic validation experiments revealed that our prototype inhibitor targets the inner membrane transporter MmpL3. Conditional gene expression of mmpL3 in mycobacteria and analysis of inhibitor-treated cells validate MmpL3 as essential for mycobacterial growth and support the involvement of this transporter in the translocation of trehalose monomycolate across the plasma membrane.     

Defective pro-IL-1β responses in macrophages from aged mice

Background

Cytokines regulated by the inflammasome pathway have been extensively implicated in various age-related immune pathologies. We set out to elucidate the contribution of the nod-like receptor protein 3 (NLRP3) inflammasome pathway to the previously described deficiencies in IL-1β production by macrophages from aged mice. We examined the production of pro-IL-1β and its conversion into IL-1β as two separate steps and compared these cytokine responses in bone marrow derived macrophages from young (6–8 weeks) and aged (18–24 months) C57BL/6 mice.

Findings

Relative to macrophages from young mice, macrophages from aged mice produced less pro-IL-1β after TLR4 stimulation with LPS. However upon activation of the NLRP3 inflammasome with ATP, macrophages from young and aged mice were able to efficiently convert and secrete intracellular pro-cytokines as functional cytokines.

Conclusions

Lower levels of IL-1β production are a result of slower and lower overall production of pro-IL-1β in macrophages from aged mice.

     

Human embryonic stem cells have constitutively active Bax at the Golgi and are primed to undergo rapid apoptosis

Human embryonic stem (hES) cells activate a rapid apoptotic response after DNA damage but the underlying mechanisms are unknown. A critical mediator of apoptosis is Bax, which is reported to become active and translocate to the mitochondria only after apoptotic stimuli. Here we show that undifferentiated hES cells constitutively maintain Bax in its active conformation. Surprisingly, active Bax was maintained at the Golgi rather than at the mitochondria, thus allowing hES cells to effectively minimize the risks associated with having preactivated Bax. After DNA damage, active Bax rapidly translocated to the mitochondria by a p53-dependent mechanism. Interestingly, upon differentiation, Bax was no longer active, and cells were not acutely sensitive to DNA damage. Thus, maintenance of Bax in its active form is a unique mechanism that can prime hES cells for rapid death, likely to prevent the propagation of mutations during the early critical stages of embryonic development.