, 2005). In addition, emphysema was observed

8 and 16 weeks following cigarette smoke exposure in the knockout mice, whereas no pathological abnormalities were observed in wild-type mice. Similarly, Gebel et al. confirmed the protective nature of Nrf2 against the development of emphysema in cigarette smoke exposed wild type mice versus Nrf2 knockout mice, and further investigated the relationships between Nrf2 and inflammation and cell cycle arrest ( Gebel et al., 2010). Comandini et EPZ-6438 in vitro al. conducted a meta-analysis of eight genomic studies on the mechanisms of smoke-induced lung damage in healthy smokers, COPD smokers and non-smokers ( Comandini et al., 2010). They found the Nrf2-mediated oxidative stress response Pathway to be the most significantly altered pathway in healthy smokers compared to non-smokers. In contrast, the Nrf2 pathway was not significantly differentially expressed in COPD smokers, indicating that Nrf2-regulated genes play a key role in protecting against buy FK228 the toxic effects of TSC. The authors suggest that the response of Nrf2-regulated

genes may potentially be used as a biomarker for COPD susceptibility. In the present study, we found that the NRF2-Mediated Oxidative Stress Response Pathway is also an important component of the toxicological response to MSC. IPA analyses identified it as one of the top five pathways for both time points and all concentrations of MSC, except for the lowest concentration at the 6 + 4 h time point (Table 3). A comparison of the Nrf2 pathway at the 6 h time point for the highest exposure concentrations of TSC and MSC shows many similarities ( Fig. 6). The Nrf2 gene itself was up-regulated along with several basic leucine zipper family transcription factors such as Jun, Atf4, and Maff. In addition, several antioxidant and stress response proteins such as Nqo1, Prdx1, Hmox1, Etomidate Sod, Txnrd1, Herpud1, Dnajb1/9 were up-regulated. Other studies have also noted that these genes are up-regulated following cigarette smoke exposure ( Bosio et al., 2002, Iizuka

et al., 2005 and Rangasamy et al., 2004). However, a notable difference between the two condensates studied here is that Gclc and Gclm, the rate limiting enzymes in glutathione synthesis, were significantly up-regulated by TSC (approximately 4 fold), but were not statistically significantly affected in MSC exposed cells (approximately 1.8 fold up-regulated). Furthermore Gsta genes were up-regulated in TSC and Gstm genes were down-regulated in MSC exposed cells. These findings were further confirmed by the significant up-regulation of the Glutathione Metabolism Pathway in tobacco exposed cells at all times and concentrations and the significant down-regulation of this pathway in marijuana exposed cells, particularly at the high concentration at the 6 + 4 h time point. These results suggest that exposure to MSC elicits more severe oxidative stress than exposure to TSC.

, 2007). The introduction of the meta-nitrophenylamine group in C-3 of nor-beta, leading to QPhNO2, could increase its growth inhibitory effects toward HL-60 cells, regardless of the incubation period. It is interesting to note that while QPhNO2 presents a higher Selleck Galunisertib IC50 value (0.91 μM)

after 72 h incubation, the other quinones, nor-beta and doxorubicin, presented a clear time-dependency, increasing their activity after 72 h. Quinones are redox active molecules that form semiquinones and hydroquinones that can redox cycle in the presence of oxygen, leading to the formation of reactive oxygen species (ROS) (Asche, 2005, de Abreu et al., 2002a, Hillard et al., 2008 and Ferreira et al., 2009). In fact, it is postulated that ROS generation SRT1720 cell line and the alkylation of cellular nucleophiles, including DNA and enzymes with a –SH group, account for the mechanism of cytotoxic action of drugs containing a quinone moiety (Asche, 2005, de Abreu et al., 2002a, Hillard et al., 2008 and Ferreira et al., 2009). In view of this fact, we measured the cytotoxic effect of QPhNO2 in the presence of NAC, an antioxidant that acts as a ROS scavenger (Zafarullaha et al., 2003). The IC50 value for QPhNO2 increased from 0.32 to 1.03 μM and that for nor-beta increased from 2.01 to 2.72 μM (Table 1, column 3). While these data suggest the participation of ROS in QPhNO2 cytotoxic effects,

they do not exclude other direct targets. Doxorubicin effects, in contrast, were not affected by NAC treatment (Table 1). ROS production was also evaluated in HL-60 cells by flow cytometry using the oxidation-sensitive fluorescent dye H2-DCF-DA after 1 h of incubation. QPhNO2 and nor-beta stimulated ROS generation, while doxorubicin was inactive (Fig. 2). ROS generation was higher in the first hour than after 3 h of incubation (data not shown). The pre-incubation with

NAC protected the cells from oxidative stress, reducing intracellular ROS generation. Cell death can be classified according to its morphological appearance, which may be apoptotic, necrotic, http://www.selleck.co.jp/products/Gemcitabine(Gemzar).html autophagic or associated with mitosis catastrophe (Melino, 2001 and Okada and Mak, 2004). Cells undergoing apoptosis show typical well-defined morphological changes, including plasma membrane blebbing, chromatin condensation with margination of chromatin to the nuclear membrane, karyorrhexis (nuclear fragmentation), and formation of apoptotic bodies (Kerr et al., 1972), as already described. Cells treated with QPhNO2 displayed those features, suggesting that this compound induces apoptosis in HL-60 leukemia cells (data not shown). Considering the observed morphological features, we conducted a flow cytometry analysis of several cellular and biochemical events to assess the mechanisms involved in cell death induced by the tested compounds.

Modern sunscreens may contain at least two UV filters, one with optimal performance in the UVA region and the other one in the UVB region. However, the presence of different UV filters, which usually leads to synergistic effects ZD6474 in vivo regarding both the final performance and photostabilization of the sunscreen, can also accelerate their decomposition if a photoreaction occurs between the single components (Osterwalder and Herzog, 2010, Gonzalez et al., 2007, Chatelain and Gabard, 2001 and Lhiaubet-Vallet et al., 2010). Despite the wide range of UVB filters, appropriate UVA filters are rare; among them avobenzone is probably the most important

representative. This active ingredient is present in numerous commercial sunscreen and cosmetic formulations. Avobenzone strongly absorbs UVA, but presents significant degradation under UV exposure reducing its UVA protecting effect (Paris et al., 2009 and Bouillon, 2000). The reactive intermediates of photounstable filter substances come into direct contact with the skin, where

they may behave as photo-oxidants or may also promote phototoxic or photoallergic contact dermatitis. The interaction of photodegradation products with sunscreen excipients or skin components like sebum may lead to the formation of newmolecules with unknown toxicological properties (Cambon et al., 2001, Deleo et al., 1992, Rieger, 1997, Schrader et al., 1994 and Nohynek and Schaefery, 2001). Consequently, IOX1 concentration there is an increasing concern

about the phototoxicity and photoallergy of UV filters. Phototoxicity is defined as a toxic response from a substance applied to the body which is either elicited or increased (apparent at lower dose levels) after subsequent exposure to light, or that is induced by skin irradiation after systemic administration of a substance (OECD, 2004). It is as a non-immunological light-induced skin response (dermatitis) to a photoactive chemical, and the skin response is characterized by erythema and sometimes edema, vesiculation, and pigmentation. Phototoxic reactions are comparable with primary irritation reactions in that they may be elicited after a single exposure, thus no induction period is required (Marzulli and Glutamate dehydrogenase Maibach, 1985). Photoallergic contact dermatitis is thought to arise when UV radiation interacts with a chemical to form a hapten or antigen, which in turn triggers a type IV hypersensitivity reaction (Bryden et al., 2006). As organic UV filters are used in increasing amounts, there is gradual emergence of reports of allergic and photoallergic reactions to UV filters on human skin. Epidemiological studies performed using human photopatch test, showed that avobenzone and many other UV-filters were the causal agents of these allergic and photoallergic reactions (Schauder and Ippen, 1997 and Lodén et al., 2011).

She started her scientific career in the Laboratory

of Toxicology under the supervision of Milutin Vandekar with methodological aspects of the determination of acetylcholine hydrolysis using the Warburg apparatus (Vandekar and Reiner, www.selleckchem.com/products/cb-839.html 1962). During her Alexander v. Humboldt scholarship at the Institute of Physiology at the University of Heidelberg headed by Wolfgang Hardegg she employed this method for the detection of several acetylcholine hydrolyzing enzymes in purified horse serum preparations that was published in Nature (Reiner et al., 1965). Next, Elsa Reiner spent some seven years in the M.R.C. Laboratories at Carshalton, Sussex, where a lot of this website important enzyme kinetic studies were published together with the late Norman Aldridge, culminating in their standard textbook “Enzyme inhibitors as substrates. Interactions of esterases with esters of organophosphorus and carbamic acids (Aldridge and Reiner, 1972). This legacy of the two important scientists is still a mostly cited book and a “must” for the cholinesterase community. Coming back to her Laboratory of Biochemistry at IMI in Zagreb, which she led until

her (official!) retirement in 2000, important enzyme kinetic studies on cholinesterases appeared with her coworkers Vera Simeon and Mira Skrinjaric-Spoljar during the 1970s and 1980s. The field was extended to structural aspects when Zoran Radić joined the scene. The importance of an allosteric peripheral binding site in cholinesterases was elaborated together with Palmer Taylor at La Jolla and resulted in the most often cited article of Elsa Reiner’s bibliography Dichloromethane dehalogenase (Radić et al., 1991). In the 1990s Elsa

Reiner turned to another group of mammalian esterases with the capability of splitting organophosphorus compounds, the so-called paraoxonases, including phenotyping studies. These studies touched nomenclatural aspects, which resulted in a joined publication with La Du et al. (1999). At the end of the last century, Zrinka Kovarik met the group and continued investigations on the relationship of structural aspects on functional properties of cholinesterases. It is she who heads her laboratory at IMI now. Even if Elsa Reiner had (formally!) retired, she was still active and gave her input in the scientific work almost until her passing. “E. Reiner led the Laboratory of Biochemistry with a strong hand and high professional skill, but also with sensitivity for everyday life and family problems for which we are very thankful to her” wrote her old co-worker Blanka Krauthacker in 2008. Besides these fundamental studies many applied aspects were touched by Elsa Reiner who placed her wide knowledge at the disposal, e.g. of the World Health Organization where she was an Expert Panel Member for almost 30 years.

The frequencies of the mild and severe phenotypes were quantitatively evaluated as shown in Figs. 7B–D. Approximately 14% of zmsi1 KD embryos exhibited a severe phenotype in which the embryo had a very small head and tail, and insufficient formation of the eyes ( Fig. 7C). The severe group appeared to also have pericardial edema. Another 46% of zmsi1 KD exhibited a mild phenotype, in which the embryo showed a slight microcephaly

and lateral curvature of the shortened spine and fin ( Fig. 7D). In both cases, these zebrafish embryos could not swim normally and the mortality rate was higher than for the control groups ( Fig. 7E). The frequency of the microcephaly find more phenotype is shown in Fig. 7F. Representative embryos defining the normal, mild and severe phenotypes are shown in Figs. 7B–D. To confirm the reproducibility of the KD phenotype, a second MO experiment was performed, in which a 25-bp MO with a completely different sequence was used to target zmsi. The frequencies of the phenotypes were similar to the first MO KD ( Fig. 7F). To confirm the

phenotype specificity, we next performed rescue experiments with purified recombinant protein from several species (Supplementary Fig. 2A). The frequency of the microcephaly phenotype decreased with the injection of zebrafish, mouse or human Msi1 protein, which were purified via their HA-tags (Fig. 7F). A statistical analysis comparing the frequency of the rescued phenotype between the KD and rescued samples indicated that the only significant difference Inhibitor Library datasheet was in the severe phenotype MG-132 purchase group. The severe phenotype was rescued by zMsi1 injection (p = 0.003), as well as by injection of the mouse (p = 0.013) or human (p = 0.010) protein. Injection of the zMsi1 protein without MO resulted in a significant increase in whole body size by day 3 (72 hpf) compared to wild-type embryos (Supplementary Figs. 2C–E). The reason why this over-expression phenotype was not restricted to the CNS is unclear; however, the injected HA-tagged protein

was detected diffusely throughout the entire embryo. To examine the hypoplasia of the CNS, a specific marker transgenic zebrafish was used. The green fluorescent protein (GFP) transgenic zebrafish Tg(elavl3:EGFP)zf8 (Park et al., 2000), designated HuC:GFP, was used in a zmsi1 KD analysis. The HuC:GFP transgenic strain was used to observe neural tissue formation over the course of development because the expression of GFP is controlled by the promoter of a neural tissue-specific RBP, HuC ( Figs. 7G–J). In the zmsi1 KD in HuC:GFP zebrafish, a limited number of GFP positive cells were detected due to hypoplasia of the neural tissue in both the brain and spinal cord ( Figs. 7G and H). Finally, the effectiveness of the MO KD of zMsi was evaluated by anti-Msi1 immunohistochemistry using frozen sections from 48 hpf embryonic spinal cord.

Several lines of evidence, however, show that all neoplasms, not just those arising on the background of chronic inflammation, thrive with inflammatory cell stimuli. Indeed, many times the tumor elicited immune response is unable to eliminate a rapidly growing population of cells that is always one step ahead due to the natural selection advantage. Instead, it shapes the tumor stroma in favor of cancer cell survival and expansion

in a manner similar to that observed in tissue remodeling and repair [2], [3], [6] and [7]. In that sense, the view of cancer as “a wound that does not heal” [10] has been further solidified. Consequently, key regulators of wound healing, such as immune cells and proteases, are now recognized Ceritinib concentration as fundamental rather than secondary players in neoplasmatogenesis [3]. One such regulator is urokinase-type plasminogen activator (uPA), a protease that has a dominant role in the proteolytic network and is primarily involved in fibrinolysis, tissue remodeling, and cell migration [11], [12], [13] and [14]. uPA catalyzes the conversion of plasminogen to plasmin and also activates other important proteases, including cathepsin B and matrix metalloproteinases. The targets of uPA in turn activate an array of proteins with a broad spectrum of biologic activities [13] and [14]. In the tumor microenvironment, the complex cascades initiated

by uPA check details promote tumor progression. First, they facilitate neoplastic cell invasion, motility, and metastasis by degrading epithelial basement

membranes and the extracellular matrix. Second, they support tumor growth by stroma remodeling and angiogenesis. Finally, they are involved in proliferating and antiapoptotic tumor cell signaling [8], [14], [15], [16], [17] and [18]. These facts, supported by many studies in both animal models [19], [20], [21], [22], [23] and [24] and humans [15] and [25], have placed uPA among the tumor promoting molecules with emerging importance. To date, uPA is considered as a poor prognosis factor and a potential therapeutic target for most types of cancer including colorectal cancer [15], [25] and [26]. Transforming growth factor–β1 Buspirone HCl (TGF-β1) is one of the most important factors activated by the uPA-generated plasmin [14] and [27]. TGF-β1 is ubiquitously produced by a variety of cells and excreted in the extracellular matrix in a latent form. The cleavage of this form by plasmin results in the production of the biologically active TGF-β1 [28], which has been shown to act as a tumor suppressor in the early stages of tumor development and as a major regulator of immune events in the tumor microenvironment [29] and [30]. As with the corruption of normal TGF-β1 signaling pathways at the gene level [29] and [30], the lack of extracellular active TGF-β1 protein may also increase the risk of cancer initiation. Following this reasoning, we hypothesized that uPA and TGF-β1 may have an interlinked tumor-suppressive function.

As cathepsin L prefers a hydrophobic residue at P2 and cathepsin B prefers an arginine at the same position ( Barrett et al., 1998), S. levis

cysteine proteinase is a cathepsin L-like proteinase. Its molecular mass, as determined by SDS-PAGE (37 kDa), is somewhat larger than and its optimal pH (6.0) is similar to known insect cathepsin L-like proteinases (see, for example, BGB324 Cristofoletti et al., 2005). The food ingested by insects generally passes through the foregut and is enclosed by the PM in the midgut, where it is digested first by enzymes that penetrate into the endoperitrophic space (inside the PM), then by enzymes acting on diffuse material in the ectoperitrophic space (between the PM and midgut epithelium) and finally on the midgut cell surface (Terra and Ferreira, 1994 and Terra and Ferreira, 2005).

The PM is a film that surrounds the food bolus in most insects and is formed by a network of chitin and proteins to which enzymes and other components associate. selleck screening library This structure shares with the ancestral gastrointestinal mucus the functions of protection against food abrasion and microorganisms, but also has specific functions in digestion associated to the compartmentalization of luminal contents (Terra, 2001 and Bolognesi et al., 2008). Occasionally, the film surrounding the food may have a gel consistency, forming a non-membranous structure known as peritrophic gel (PG) (Terra, 2001 and Terra and Ferreira, 2005). The presence of a conspicuous PM in S. levis was confirmed by dissection only in the middle and posterior regions of the midgut, whereas the observations of the present study indicate the occurrence of a PG in the anterior midgut. Enzyme assays in S. levis demonstrated that the initial digestion of starch must be carried out by amylase in the anterior and middle portions of the midgut, whereas final starch digestion

must be performed by maltase. Protein digestion starts under the action of a cathepsin L-like proteinase in the anterior and middle midgut, Exoribonuclease continues with trypsin in middle and posterior midgut and finishes on the surface of cells in the middle and posterior midgut by a membrane-bound aminopeptidase. Soluble trypsin and capthepsin L-like enzymes found associated with midgut tissue probably correspond to enzyme molecule entrapped in the cell glycocalyx, as shown in other beetles ( Ferreira et al., 1990). Membrane-bound trypsin has been described in other insect midguts and seems to be enzyme molecules en route to be secreted ( Terra and Ferreira, 1994 and Terra and Ferreira, 2005). The activities of amylase, cysteine proteinase and trypsin decrease throughout the contents of the midgut. This is what one would expect when there is a flux of fluid from the posterior midgut to the anterior midgut in the ectoperitrophic space, as described for most insects (for reviews, see Terra and Ferreira, 1994 and Terra and Ferreira, 2005).

None of the respondents indicated that the damages caused their businesses to close permanently and, despite sustaining financial losses, these mTOR inhibitor businesses have since been able to rebuild. Only two respondents indicated that the negative impact of the hurricane on their business meant they needed to rely on alternative income sources (e.g. carpentry and restaurant work) ( Table 5). Several respondents noted that as a result of the severe impacts of hurricane Luis on Anguilla, it is now common-place for hotels on the

island to close during the hurricane season (n=3). Many respondents (n=8) stated they would be concerned if hurricane risk increased, because of the implications of the hurricane season on tourism and the impacts sustained from hurricane Luis. Only two respondents said that they were not worried about hurricane risk. Like the fishers, perceptions regarding climate change elicited relatively few responses (n=5) from the tourist operators ( Table 6). The climate change related threats that were of concern included increasing water temperature and coral bleaching (n=2), changing weather and tide patterns

(n=2) and the increasing risk of hurricanes (n=1). When the tourist operators were asked RG7204 specifically for their perceptions on the condition of the coral reef ecosystems, eight respondents stated that they had witnessed negative changes in the state of the reefs during their lifetime (i.e. physical damage to reefs (n=5), reduction in coral

cover (n=3), and loss of colour or bleaching (n=2)). Hurricane and storm damage was mentioned by most respondents (n=10) as the primary cause of coral reef decline in Anguilla. The second most commonly mentioned stressor was fishing (n=8), and respondents spoke of the combination of too many fishers, irresponsible fishing practices and a lack of enforcement leading to major declines in fish and shellfish abundance, with knock-on implications for the coral reef. Increased prevalence of coral bleaching Dipeptidyl peptidase was a concern of some tourist operators (n=3). Additional changes to the coral reefs were also mentioned by individual respondents, including the growing prevalence of algae, damage caused to reefs by boat anchors and marine-based pollution. The majority of respondents (n=11, 85%) stated that coral reef condition affects their business, because unhealthy coral reefs mean there are fewer fish, and their client-base wishes to see fish and coral. Several respondents also referred to tourist demand for seafood, and that coral reef condition affects this aspect of the tourism market. Many Caribbean islands are heavily dependent on tourism and fisheries for livelihood opportunities.

g., body fluids) onto their surface. The adsorption process is influenced by surface energy, surface charge and the affinity to specific biomolecules. Hydrophilic silica can effectively adsorb high-molecular proteins of synthetic and natural origin. Dutta and co-workers showed that the protein adsorption profiles for 50–1000-nm amorphous silica particles were comparable ( Dutta et al., 2007). Silica particles may also adsorb bronchoalveolar lining fluid components, including

lung surfactant and proteins, such as the surfactant protein D (SP-D) ( Hamilton et al., 2008). Hence, before inhaled silica particles come into contact with alveolar macrophages, lung surfactant composed of phospholipids and surfactant ABT-263 research buy proteins (SP) could potentially coat the outer surface of the silica particles modifying the surface chemistry and ultimately influence the toxicity ( Hamilton et al., 2008). A high specific surface area may promote the adsorption of

Erastin order peptides and proteins contained in the alveolar lining fluid. Though agglomerated and aggregated particles in the μm range might theoretically be broken down to the size of the primary nanoparticle within the body, research results show the robustness of aggregates and agglomerates to disaggregation, even in the context of high-energy processing (Maier et al., 2006). The denaturation of cell membrane proteins by proton-donating silanol groups is the major underlying mechanism for membrane damage. Pandurangi et al. (1990) found a strong correlation between surface silanol groups (Si O H) and the haemolytic activity of amorphous silica and suggested that the surface hydrogen of silica bonds to protein components of the membrane and subsequently abstracts these proteins from the membrane. The haemolytic activity is highly specific for silanol and seems to depend only on the concentration PRKACG of negatively charged silanol groups that are accessible by the cell membranes of erythrocytes (Slowing et al., 2009). A strong distortion of the membrane

after interaction with silica particles can lead to loss of membrane flexibility and resiliency as well as the release of haemoglobin (haemolysis). The agglutination of erythrocytes can be enhanced due to interaction with aggregates of SAS particles which prevent the electrostatic repulsive interaction of negatively charged cells due to the strong interaction of SAS particles with proteins integrated into the cell membranes (Chuiko, 2003). In contrast, the haemolytic potential of hydrophobic silica particles with a siloxane surface structure is low. Translocation of particles into cells is dependent on interactions with the cell membrane, i.e., processes of endocytosis (mainly pinocytosis and phagocytosis or receptor-mediated endocytosis).

Schmaier Eva Schmelzer Marcus Schwaiger Frank Sciurba James A. Shayman Donna Shewach Rebecca Shilling Vijay Shivaswamy Imad Shureiqi Stephen Skaper Melissa Snyder Osama Soliman Peter Sporn Jack Stapleton Sokrates Stein Arthur Strauch Bodo Eckehard Strauer LY2157299 mw Jakob Strom Hong-shuo Sun Mark Sussman Kathy Svoboda Andrew Talal Sakae Tanaka Jose Tanus-Santos Milton Taylor Beverly Teicher Patricia Teixeira Daniela Tirziu Jorn Tongers Jordi Torrelles Niels Tørring Cory Toth George C. Tsokos Antonino Tuttolomondo

Dimitrios Tziafas Mark Udden Mohammad Uddin Terry G. Unterman Celalettin Ustun Nosratola Vaziri Jelena Vekic Hector Ventura Gregory M. Vercellotti Vassilis Voudris Jil Waalen Hiroo Wada Richard L. Wahl Qin Wang Chunyu Wang Lorraine Ware Saman Warnakulasuriya Donald Wesson Christof Westenfelder “
“The Editors of Translational Research have retracted the article titled “Desalted deep-sea water improves cognitive function in mice by increasing the production of insulin-like growth factor-I in the hippocampus” by Harada et al. After an Investigation Committee on Scientific Misconduct was formed at Nagoya City University to investigate 19 articles written by Drs. Naoaki

Harada and Kenji Okajima, the committee brought one article, published in Translational Research, to our attention. The committee concluded that Figures 4D, 4E, 4G and 4H in Translational Research (Harada et al., 2011) were derived from the same photograph as Figures 8D, 8E, 8G Amisulpride and 8H in the Journal selleckchem of Pharmacology and Experimental Therapeutics (Narimatsu et al., 2009). While Figures D and G represent control data in both articles, Figures 4E and 4H and Figures 8E and 8H represent data from two different sets of animals treated with either desalted deep sea water or donepezil, respectively. The Nagoya City University

Committee concluded that Figure 4 in Translational Research (Harada et al., 2011) contains fabricated data. After the Committee pointed out these fabrications to the authors, they replaced Figures 4A-4I and an Erratum was published in Translational Research (Transl Res. 2011 Dec;158(6):387). However, the Committee has informed us that they have been unsuccessful in confirming that the new figures are the appropriate ones. Attempts to contact Drs. Harada and Okajima were made through the Nagoya Committee, and the authors declined to respond. The Editors “
“We wish to acknowledge the outstanding contribution of our reviewers and Editorial Advisory Board. The quality and breadth of the Journal is only made possible by the dedicated efforts of our reviewers. Joseph Ahearn S. Ansar Ahmed Ziyad Al-Aly Mary Alpaugh Ajjai Alva Elias Anaissie David Archer Lois Arend Robert F. Ashman Muhammad Ashraf Ravi Ashwath Pal Aukrust Edwin Avery Abul Azad Rathindranath Baral Robert P.