Frequency of Retinal Redetachment Based on the Primary Reattachment Treatment and Intraocular Tamponade

Introduction: To observe the number and presentation of retinal redetachment after primary reattachment treatment in a national eye center. Methods: This study was designed for ob- servational-descriptive of the medical record from April 2011 to March 2012. Selected cases were identified on the secondary retinal surgery for retinal reattachment followed the failure of the primary treatment. Cases were then classified into 4 groups based on the primary reattach- ment procedure: pneumatic retinopexy (PR), scleral buckle (SB), pars plana vitrectomy (PPV), and combined SB with PPV. Furthermore, in the group of PPV and SB+PPV were then divided into 3 subgroups based on the intraocular tamponade: SF6 gas, silicone oil, and heavy silicone oil. Results: At one-year followed-up data, the presentation retinal redetachment was 7.1%, relative to the sex female (26%) was less than male (74%) with the most common age group was 41-50 years-old. Regarding with primary reattachment treatment, cases of retinal redetachment after pneumatic retinopexy was 6%, the scleral buckle was 16%, pars plana vitrectomy was 29%, and combined sclera buckle with pars plana vitrectomy was 48%. Con- clusions: Rates of retinal redetachment after primary reattachment treatment varied from 6% to 48%, that were performed by combined scleral buckling and pars plana vitrectomy with or without tamponade silicone oil

Tailoring the specificity of the type C feruloyl esterase FoFaeC from Fusarium oxysporum towards methyl sinapate by rational redesign based on small molecule docking simulations

The type C feruloyl esterase FoFaeC from Fusarium oxysporum is a newly discovered enzyme with high potential for use in the hydrolysis of lignocellulosic biomass but it shows low activity towards sinapates. In this work, small molecule docking simulations were employed in order to identify important residues for the binding of the four model methyl esters of hydroxycinnamic acids, methyl ferulate/caffeate/sinapate/p-coumarate, to the predicted structure of FoFaeC. Subsequently rational redesign was applied to the enzyme’ active site in order to improve its specificity towards methyl sinapate. A double mutation (F230H/T202V) was considered to provide hydrophobic environment for stabilization of the methoxy substitution on sinapate and a larger binding pocket. Five mutant clones and the wild type were produced in Pichia pastoris and biochemically characterized. All clones showed improved activity, substrate affinity, catalytic efficiency and turnover rate compared to the wild type against methyl sinapate, with clone P13 showing a 5-fold improvement in catalytic efficiency. Although the affinity of all mutant clones was improved against the four model substrates, the catalytic efficiency and turnover rate decreased for the substrates containing a hydroxyl substitution

Engineering tyrosine-based electron flow pathways in proteins: The case of aplysia myoglobin

Tyrosine residues can act as redox cofactors that provide an electron transfer ("hole-hopping") route that enhances the rate of ferryl heme iron reduction by externally added reductants, for example, ascorbate. Aplysia fasciata myoglobin, having no naturally occurring tyrosines but 15 phenylalanines that can be selectively mutated to tyrosine residues, provides an ideal protein with which to study such through-protein electron transfer pathways and ways to manipulate them. Two surface exposed phenylalanines that are close to the heme have been mutated to tyrosines (F42Y, F98Y). In both of these, the rate of ferryl heme reduction increased by up to 3 orders of magnitude. This result cannot be explained in terms of distance or redox potential change between donor and acceptor but indicates that tyrosines, by virtue of their ability to form radicals, act as redox cofactors in a new pathway. The mechanism is discussed in terms of the Marcus theory and the specific protonation/deprotonation states of the oxoferryl iron and tyrosine. Tyrosine radicals have been observed and quantified by EPR spectroscopy in both mutants, consistent with the proposed mechanism. The location of each radical is unambiguous and allows us to validate theoretical methods that assign radical location on the basis of EPR hyperfine structure. Mutation to tyrosine decreases the lipid peroxidase activity of this myoglobin in the presence of low concentrations of reductant, and the possibility of decreasing the intrinsic toxicity of hemoglobin by introduction of these pathways is discussed. © 2012 American Chemical Society

FREQUENCY OF RETINAL REDETACHMENT BASED ON THE PRIMARY REATTACHMENT TREATMENT AND INTRAOCULAR TAMPONADE

ABSTRACT Introduction: To observe the number and  presentation of retinal redetachment after primary reattachment treatment in a national eye  center. Methods:  This study was designed for ob- servational-descriptive of the medical record  from April 2011  to March 2012.  Selected cases were identified on the secondary retinal surgery for retinal reattachment followed the failure of the primary treatment. Cases were then classified into 4 groups based on the primary reattach- ment procedure: pneumatic retinopexy (PR), scleral buckle (SB), pars plana vitrectomy (PPV), and combined SB with PPV. Furthermore, in the group of PPV and SB+PPV  were then divided into 3 subgroups based on the intraocular tamponade: SF6  gas, silicone oil, and heavy  silicone oil. Results:  At one-year followed-up data, the presentation retinal redetachment was 7.1%, relative to the sex female (26%) was less than  male (74%) with the most common age  group was 41-50  years-old. Regarding with primary reattachment treatment, cases  of retinal redetachment after pneumatic retinopexy was 6%,  the  scleral buckle was 16%,  pars plana vitrectomy was 29%, and  combined sclera buckle with pars plana vitrectomy was 48%. Con- clusions: Rates of retinal redetachment after primary reattachment treatment varied from 6% to 48%, that were  performed by combined scleral buckling and  pars plana vitrectomy with or without tamponade silicone oil. Keyword : Retinal redetachment, pars plana vitrectomy, scleral buckle, silicon oil, intraocular gas

Spectral Decomposition of Regulatory Thresholds for Climate-Driven Fluctuations in Hydro- and Wind Power Availability

Abstract Climate-driven fluctuations in the runoff and potential energy of surface water are generally large in comparison to the capacity of hydropower regulation, particularly when hydropower is used to balance the electricity production from covarying renewable energy sources such as wind power. To define the bounds of reservoir storage capacity, we introduce a dedicated reservoir volume that aggregates the storage capacity of several reservoirs to handle runoff from specific watersheds. We show how the storage bounds can be related to a spectrum of the climate-driven modes of variability in water availability and to the covariation between water and wind availability. A regional case study of the entire hydropower system in Sweden indicates that the longest regulation period possible to consider spans from a few days of individual subwatersheds up to several years, with an average limit of a couple of months. Watershed damping of the runoff substantially increases the longest considered regulation period and capacity. The high covariance found between the potential energy of the surface water and wind energy significantly reduces the longest considered regulation period when hydropower is used to balance the fluctuating wind power

Pharmacological development of target-specific delocalized lipophilic cation-functionalized carboranes for cancer therapy

PURPOSE: Tumor cell heterogeneity and microenvironment represent major hindering factors in the clinical setting toward achieving the desired selectivity and specificity to malignant tissues for molecularly targeted cancer therapeutics. In this study, the cellular and molecular evaluation of several delocalized lipophilic cation (DLC)-functionalized carborane compounds as innovative anticancer agents is presented. METHODS: The anticancer potential assessment of the DLC-carboranes was performed in established normal (MRC-5, Vero), cancer (U-87 MG, HSC-3) and primary glioblastoma cancer stem (EGFRpos, EGFRneg) cultures. Moreover, the molecular mechanism of action underlying their pharmacological response is also analyzed. RESULTS: The pharmacological anticancer profile of DLC-functionalized carboranes is characterized by: a) a marked in vitro selectivity, due to lower concentration range needed (ca. 10 fold) to exert their cell growth-arrest effect on U-87 MG and HSC-3, as compared with that on MRC-5 and Vero; b) a similar selective growth inhibition behavior towards EGFRpos and EGFRneg cultures (>10 fold difference in potency) without, however, the activation of apoptosis in cultures; c) notably, in marked contrast to cancer cells, normal cells are capable of recapitulating their full proliferation potential following exposure to DLC-carboranes; and, d) such pharmacological effects of DLC-carboranes has been unveiled to be elicited at the molecular level through activation of the p53/p21 axis. CONCLUSIONS: Overall, the data presented in this work indicates the potential of the DLC-functionalized carboranes to act as new selective anticancer therapeutics that may be used autonomously or in therapies involving radiation with thermal neutrons. Importantly, such bifunctional capacity may be beneficial in cancer therapy

Identification and Characterization of Alternative Promoters, Transcripts and Protein Isoforms of Zebrafish R2 Gene

Ribonucleotide reductase (RNR) is the rate-limiting enzyme in the de novo synthesis of deoxyribonucleoside triphosphates. Expression of RNR subunits is closely associated with DNA replication and repair. Mammalian RNR M2 subunit (R2) functions exclusively in DNA replication of normal cells due to its S phase-specific expression and late mitotic degradation. Herein, we demonstrate the control of R2 expression through alternative promoters, splicing and polyadenylation sites in zebrafish. Three functional R2 promoters were identified to generate six transcript variants with distinct 5′ termini. The proximal promoter contains a conserved E2F binding site and two CCAAT boxes, which are crucial for the transcription of R2 gene during cell cycle. Activity of the distal promoter can be induced by DNA damage to generate four transcript variants through alternative splicing. In addition, two novel splice variants were found to encode distinct N-truncated R2 isoforms containing residues for enzymatic activity but no KEN box essential for its proteolysis. These two N-truncated R2 isoforms remained in the cytoplasm and were able to interact with RNR M1 subunit (R1). Thus, our results suggest that multilayered mechanisms control the differential expression and function of zebrafish R2 gene during cell cycle and under genotoxic stress

Spectroscopic Studies of the Iron and Manganese Reconstituted Tyrosyl Radical in Bacillus Cereus Ribonucleotide Reductase R2 Protein

Ribonucleotide reductase (RNR) catalyzes the rate limiting step in DNA synthesis where ribonucleotides are reduced to the corresponding deoxyribonucleotides. Class Ib RNRs consist of two homodimeric subunits: R1E, which houses the active site; and R2F, which contains a metallo cofactor and a tyrosyl radical that initiates the ribonucleotide reduction reaction. We studied the R2F subunit of B. cereus reconstituted with iron or alternatively with manganese ions, then subsequently reacted with molecular oxygen to generate two tyrosyl-radicals. The two similar X-band EPR spectra did not change significantly over 4 to 50 K. From the 285 GHz EPR spectrum of the iron form, a g1-value of 2.0090 for the tyrosyl radical was extracted. This g1-value is similar to that observed in class Ia E. coli R2 and class Ib R2Fs with iron-oxygen cluster, suggesting the absence of hydrogen bond to the phenoxyl group. This was confirmed by resonance Raman spectroscopy, where the stretching vibration associated to the radical (C-O, ν7a = 1500 cm−1) was found to be insensitive to deuterium-oxide exchange. Additionally, the 18O-sensitive Fe-O-Fe symmetric stretching (483 cm−1) of the metallo-cofactor was also insensitive to deuterium-oxide exchange indicating no hydrogen bonding to the di-iron-oxygen cluster, and thus, different from mouse R2 with a hydrogen bonded cluster. The HF-EPR spectrum of the manganese reconstituted RNR R2F gave a g1-value of ∼2.0094. The tyrosyl radical microwave power saturation behavior of the iron-oxygen cluster form was as observed in class Ia R2, with diamagnetic di-ferric cluster ground state, while the properties of the manganese reconstituted form indicated a magnetic ground state of the manganese-cluster. The recent activity measurements (Crona et al., (2011) J Biol Chem 286: 33053–33060) indicates that both the manganese and iron reconstituted RNR R2F could be functional. The manganese form might be very important, as it has 8 times higher activity

Key criteria for developing ecosystem service indicators to inform decision making

Decision makers are increasingly interested in information from ecosystem services (ES) assessments. Scientists have for long recognised the importance of selecting appropriate indicators. Yet, while the amount and variety of indicators developed by scientists seems to increase continuously, the extent to which the indicators truly inform decision makers is often unknown and questioned. In this viewpoint paper, we reflect and provide guidance on how to develop appropriate ES indicators for informing decision making, building on scientific literature and practical experience collected from researchers involved in seven case studies. We synthesized 16 criteria for ES indicator selection and organized them according to the widely used categories of credibility, salience, legitimacy (CSL). We propose to consider additional criteria related to feasibility (F), as CSL criteria alone often seem to produce indicators which are unachievable in practice. Considering CSL & F together requires a combination of scientific knowledge, communication skills, policy and governance insights and on-field experience. We present a checklist to evaluate CSL & F of your ES indicators. This checklist helps to detect and mitigate critical shortcomings in an early phase of the development process, and aids the development of effective indicators to inform actual policy decisions

Semi-Automated Image Analysis for the Assessment of Megafaunal Densities at the Arctic Deep-Sea Observatory HAUSGARTEN

Megafauna play an important role in benthic ecosystem function and are sensitive indicators of environmental change. Non-invasive monitoring of benthic communities can be accomplished by seafloor imaging. However, manual quantification of megafauna in images is labor-intensive and therefore, this organism size class is often neglected in ecosystem studies. Automated image analysis has been proposed as a possible approach to such analysis, but the heterogeneity of megafaunal communities poses a non-trivial challenge for such automated techniques. Here, the potential of a generalized object detection architecture, referred to as iSIS (intelligent Screening of underwater Image Sequences), for the quantification of a heterogenous group of megafauna taxa is investigated. The iSIS system is tuned for a particular image sequence (i.e. a transect) using a small subset of the images, in which megafauna taxa positions were previously marked by an expert. To investigate the potential of iSIS and compare its results with those obtained from human experts, a group of eight different taxa from one camera transect of seafloor images taken at the Arctic deep-sea observatory HAUSGARTEN is used. The results show that inter- and intra-observer agreements of human experts exhibit considerable variation between the species, with a similar degree of variation apparent in the automatically derived results obtained by iSIS. Whilst some taxa (e. g. Bathycrinus stalks, Kolga hyalina, small white sea anemone) were well detected by iSIS (i. e. overall Sensitivity: 87%, overall Positive Predictive Value: 67%), some taxa such as the small sea cucumber Elpidia heckeri remain challenging, for both human observers and iSIS