THEORETICAL STUDIES OF BILIPROTEIN CHROMOPHORES AND RELATED BILE PIGMENTS BY MOLECULAR ORBITAL AND RAMACHANDRAN TYPE CALCULATIONS

Ramachandran calculations have been used to gain insight into steric hindrance in bile pigments related to biliprotein chromophores. The high optical activity of denatured phycocyanin, as compared to phycoerythrin, has been related to the asymmetric substitution at ring A, which shifts the equilibrium towards the P-helical form of the chromophore. Geometric effects on the electronic structures and transitions have then been studied by molecular orbital calculations for several conjugation systems including the chromophores of phycocyanin. phytochrome P,, cations, cation radicals and tautomeric forms. For these different chromophores some general trends can be deduced. For instance, for a given change in the gross shape (e.g. either unfolding of the molecule from a cyclic-helical to a fully extended geometry, or upon out-of-plane twists of the pyrrole ring A) of the molecules under study, the predicted absorption spectra all change in a simikar way. Nonetheless, there are characteristic distinctions between the different n-systems, both in the transition energies and the charge distribution, which can be related to their known differences in spectroscopic properties and their reactivity

Model evaluation of marine primary organic aerosol emission schemes

In this study, several marine primary organic aerosol (POA) emission schemes have been evaluated using the GEOS-Chem chemical transport model in order to provide guidance for their implementation in air quality and climate models. These emission schemes, based on varying dependencies of chlorophyll <i>a</i> concentration ([chl <i>a</i>]) and 10 m wind speed (<i>U</i><sub>10</sub>), have large differences in their magnitude, spatial distribution, and seasonality. Model comparison with weekly and monthly mean values of the organic aerosol mass concentration at two coastal sites shows that the source function exclusively related to [chl <i>a</i>] does a better job replicating surface observations. Sensitivity simulations in which the negative <i>U</i><sub>10</sub> and positive [chl <i>a</i>] dependence of the organic mass fraction of sea spray aerosol are enhanced show improved prediction of the seasonality of the marine POA concentrations. A top-down estimate of submicron marine POA emissions based on the parameterization that compares best to the observed weekly and monthly mean values of marine organic aerosol surface concentrations has a global average emission rate of 6.3 Tg yr<sup>−1</sup>. Evaluation of existing marine POA source functions against a case study during which marine POA contributed the major fraction of submicron aerosol mass shows that none of the existing parameterizations are able to reproduce the hourly-averaged observations. Our calculations suggest that in order to capture episodic events and short-term variability in submicron marine POA concentration over the ocean, new source functions need to be developed that are grounded in the physical processes unique to the organic fraction of sea spray aerosol

Influence of chromophores on quarternary structure of phycobiliproteins from the cyanobacterium, Mastigocladus laminosus

Chromophores of C-phycocyanin and phycoerythrο-cyanin have been chemically modified by reduction to rubins , bleaching , photoisomerization , or perturbation with bulky substituents. Pigments containing modified chromophores, or hybrids containing modified and unmodified chromophores in individual protomers have been prepared. All modifications inhibit the association of the (aß)-protomers of these pigments to higher aggregates. The results demonstrate a pronounced effect of the state of the chromophores on biliprotein quaternary structure. It may be important in phycobi1isome assembly , and also in the dual function of biliproteins as (i) antenna pigments for photosynthesis and (ii) reaction centers for photomor-phogenesis

FRAP Analysis on Red Alga Reveals the Fluorescence Recovery Is Ascribed to Intrinsic Photoprocesses of Phycobilisomes than Large-Scale Diffusion

BACKGROUND: Phycobilisomes (PBsomes) are the extrinsic antenna complexes upon the photosynthetic membranes in red algae and most cyanobacteria. The PBsomes in the cyanobacteria has been proposed to present high lateral mobility on the thylakoid membrane surface. In contrast, direct measurement of PBsome motility in red algae has been lacking so far. METHODOLOGY/PRINCIPAL FINDINGS: In this work, we investigated the dynamics of PBsomes in the unicellular red alga Porphyridium cruentum in vivo and in vitro, using fluorescence recovery after photobleaching (FRAP). We found that part of the fluorescence recovery could be detected in both partially- and wholly-bleached wild-type and mutant F11 (UTEX 637) cells. Such partial fluorescence recovery was also observed in glutaraldehyde-treated and betaine-treated cells in which PBsome diffusion should be restricted by cross-linking effect, as well as in isolated PBsomes immobilized on the glass slide. CONCLUSIONS/SIGNIFICANCE: On the basis of our previous structural results showing the PBsome crowding on the native photosynthetic membrane as well as the present FRAP data, we concluded that the fluorescence recovery observed during FRAP experiment in red algae is mainly ascribed to the intrinsic photoprocesses of the bleached PBsomes in situ, rather than the rapid diffusion of PBsomes on thylakoid membranes in vivo. Furthermore, direct observations of the fluorescence dynamics of phycoerythrins using FRAP demonstrated the energetic decoupling of phycoerythrins in PBsomes against strong excitation light in vivo, which is proposed as a photoprotective mechanism in red algae attributed by the PBsomes in response to excess light energy

Light-Induced Energetic Decoupling as a Mechanism for Phycobilisome-Related Energy Dissipation in Red Algae: A Single Molecule Study

BACKGROUND: Photosynthetic organisms have developed multiple protective mechanisms to prevent photodamage in vivo under high-light conditions. Cyanobacteria and red algae use phycobilisomes (PBsomes) as their major light-harvesting antennae complexes. The orange carotenoid protein in some cyanobacteria has been demonstrated to play roles in the photoprotective mechanism. The PBsome-itself-related energy dissipation mechanism is still unclear. METHODOLOGY/PRINCIPAL FINDINGS: Here, single-molecule spectroscopy is applied for the first time on the PBsomes of red alga Porphyridium cruentum, to detect the fluorescence emissions of phycoerythrins (PE) and PBsome core complex simultaneously, and the real-time detection could greatly characterize the fluorescence dynamics of individual PBsomes in response to intense light. CONCLUSIONS/SIGNIFICANCE: Our data revealed that strong green-light can induce the fluorescence decrease of PBsome, as well as the fluorescence increase of PE at the first stage of photobleaching. It strongly indicated an energetic decoupling occurring between PE and its neighbor. The fluorescence of PE was subsequently observed to be decreased, showing that PE was photobleached when energy transfer in the PBsomes was disrupted. In contrast, the energetic decoupling was not observed in either the PBsomes fixed with glutaraldehyde, or the mutant PBsomes lacking B-PE and remaining b-PE. It was concluded that the energetic decoupling of the PBsomes occurs at the specific association between B-PE and b-PE within the PBsome rod. Assuming that the same process occurs also at the much lower physiological light intensities, such a decoupling process is proposed to be a strategy corresponding to PBsomes to prevent photodamage of the photosynthetic reaction centers. Finally, a novel photoprotective role of gamma-subunit-containing PE in red algae was discussed

Cell-free (RNA) and cell-associated (DNA) HIV-1 and postnatal transmission through breastfeeding

<p>Introduction - Transmission through breastfeeding remains important for mother-to-child transmission (MTCT) in resource-limited settings. We quantify the relationship between cell-free (RNA) and cell-associated (DNA) shedding of HIV-1 virus in breastmilk and the risk of postnatal HIV-1 transmission in the first 6 months postpartum.</p> <p>Materials and Methods - Thirty-six HIV-positive mothers who transmitted HIV-1 by breastfeeding were matched to 36 non-transmitting HIV-1 infected mothers in a case-control study nested in a cohort of HIV-infected women. RNA and DNA were quantified in the same breastmilk sample taken at 6 weeks and 6 months. Cox regression analysis assessed the association between cell-free and cell-associated virus levels and risk of postnatal HIV-1 transmission.</p> <p>Results - There were higher median levels of cell-free than cell-associated HIV-1 virus (per ml) in breastmilk at 6 weeks and 6 months. Multivariably, adjusting for antenatal CD4 count and maternal plasma viral load, at 6 weeks, each 10-fold increase in cell-free or cell-associated levels (per ml) was significantly associated with HIV-1 transmission but stronger for cell-associated than cell-free levels [2.47 (95% CI 1.33–4.59) vs. aHR 1.52 (95% CI, 1.17–1.96), respectively]. At 6 months, cell-free and cell-associated levels (per ml) in breastmilk remained significantly associated with HIV-1 transmission but was stronger for cell-free than cell-associated levels [aHR 2.53 (95% CI 1.64–3.92) vs. 1.73 (95% CI 0.94–3.19), respectively].</p> <p>Conclusions - The findings suggest that cell-associated virus level (per ml) is more important for early postpartum HIV-1 transmission (at 6 weeks) than cell-free virus. As cell-associated virus levels have been consistently detected in breastmilk despite antiretroviral therapy, this highlights a potential challenge for resource-limited settings to achieve the UNAIDS goal for 2015 of eliminating vertical transmission. More studies would further knowledge on mechanisms of HIV-1 transmission and help develop more effective drugs during lactation.</p&gt

Attenuated Leishmania induce pro-inflammatory mediators and influence leishmanicidal activity by p38 MAPK dependent phagosome maturation in Leishmania donovani co-infected macrophages

Promastigote form of Leishmania, an intracellular pathogen, delays phagosome maturation and resides inside macrophages. But till date limited study has been done to manipulate the phagosomal machinery of macrophages to restrict Leishmania growth. Attenuated Leishmania strain exposed RAW 264.7 cells showed a respiratory burst and enhanced production of pro-inflammatory mediators. The augmentation of pro-inflammatory activity is mostly attributed to p38 MAPK and p44/42 MAPK. In our study, these activated macrophages are found to induce phagosome maturation when infected with pathogenic Leishmania donovani. Increased co-localization of carboxyfluorescein succinimidyl ester labeled pathogenic L. donovani with Lysosome was found. Moreover, increased co-localization was observed between pathogenic L. donovani and late phagosomal markers viz. Rab7, Lysosomal Associated Membrane Protein 1, Cathepsin D, Rab9, and V-ATPase which indicate phagosome maturation. It was also observed that inhibition of V-type ATPase caused significant hindrance in attenuated Leishmania induced phagosome maturation. Finally, it was confirmed that p38 MAPK is the key player in acidification and maturation of phagosome in attenuated Leishmania strain preexposed macrophages. To our knowledge, this study for the first time reported an approach to induce phagosome maturation in L. donovani infected macrophages which could potentiate short-term prophylactic response in futur

The influence of allogenic blood transfusion in patients having free-flap primary surgery for oral and oropharyngeal squamous cell carcinoma

The influence of perioperative blood transfusion in oral and oropharyngeal squamous cell carcinoma remains uncertain. It is believed that blood transfusion downregulates the immune system and may have an influence on cancer recurrence and survival. In all, 559 consecutive patients undergoing primary surgery for oral and oropharyngeal squamous cell carcinoma between 1992 and 2002 were included in this study. Known prognostic variables along with transfusion details were obtained from head and neck cancer and blood transfusion service databases, respectively. Adjusting for relevant prognostic factors in Cox regression, the hazard ratio for patients having 3 or more transfused units relative to those not transfused was 1.52 (95% confidence interval (CI) 0.93–2.47) for disease-specific and 1.52 (95% CI 1.05–2.22) for overall mortality. Blood transfusion of 3 or more units might confer a worse prognosis in patients undergoing primary surgery for oral and oropharyngeal squamous cell carcinoma. Therefore, every effort should be made to limit the amount of blood transfused to the minimum requirement

Enamel thickness variation in the deciduous dentition of extant large-bodied hominoids

Objectives: Enamel thickness features prominently in hominoid evolutionary studies. To date, however, studies of enamel thickness in humans, great apes, and their fossil relatives have focused on the permanent molar row. Comparatively little research effort has been devoted to tissue proportions within deciduous teeth. Here we attempt to fill this gap by documenting enamel thickness variation in the deciduous dentition of extant large‐bodied hominoids. Materials and methods: We used microcomputed tomography to image dental tissues in 80 maxillary and 78 mandibular deciduous premolars of Homo sapiens, Pan troglodytes, Gorilla, and Pongo. Two‐dimensional virtual sections were created from the image volumes to quantify average (AET) and relative (RET) enamel thickness, as well as its distribution across the crown. Results: Our results reveal no significant differences in enamel thickness among the great apes. Unlike the pattern present in permanent molars, Pongo does not stand out as having relatively thicker‐enameled deciduous premolars than P. troglodytes and Gorilla. Humans, on the other hand, possess significantly thicker deciduous premolar enamel in comparison to great apes. Following expectations from masticatory biomechanics, we also find that the “functional” side (protocone, protoconid) of deciduous premolars generally possesses thicker enamel than the “nonfunctional” side. Discussion: Our study lends empirical support to anecdotal observations that patterns of AET and RET observed for permanent molars of large‐bodied apes do not apply to deciduous premolars. By documenting enamel thickness variation in hominoid deciduous teeth, this study provides the comparative context to interpret rates and patterns of wear of deciduous teeth and their utility in life history reconstructions