Illuminating otoliths: New insights for life history of Balistes triggerfishes.

Our understanding of fish life-history strategies is informed by key biological processes, such as growth, survival/mortality, recruitment and sexual maturation, used to characterize fish stocks (populations). Characterizing the life-history traits of fish populations requires the application of accurate age estimation for managed species. Grey triggerfish Balistes capriscus and queen triggerfish Balistes vetula are important reef-associated species for commercial and recreational fisheries in the Atlantic Ocean. Both species exhibit a unique reproductive strategy for large-bodied fisheries-targeted reef fishes in that they are nesting benthic spawners and invest substantial energy in defence and care of their benthic nests and fertilized eggs. Until recently, our understanding of the life-history strategies of triggerfishes assumed the main method used to obtain age estimates, increments counted from thin sections of the first dorsal spine, provided an accurate characterization of population age-based parameters. However, results from bomb radiocarbon validation studies on the two Balistes species demonstrated that spines do not provide accurate ages, but sagittal otoliths do. The main goal of the current study was to provide an updated understanding for triggerfish life-history strategies by using otolith-based age estimates to characterize population age structure and growth for grey triggerfish and queen triggerfish from waters of the south-eastern U.S. Atlantic. The current study is the first to report on sex-specific age and growth information for grey triggerfish using the Δ14 C-validated otolith-based age estimation method and the results indicate that the previous characterization of Balistes species as exhibiting moderately rapid growth and as relatively short-lived, based on spine-derived age estimates, are flawed. Otolith-based ages indicated that grey triggerfish and queen triggerfish are moderately slow-growing and long-lived species, attaining maximum ages of 21 and 40 years, respectively. Management efforts for triggerfishes should evaluate these new insights and incorporate the results of otolith-based age estimation into future population monitoring efforts.

Age and growth of grey triggerfish Balistes capriscus from trans-Atlantic populations.

Anthropogenic factors that negatively impact reef fishes can include changes in life-history patterns of fisheries-targeted species. Understanding these impacts on growth and population age structure is essential in the management of exploited populations of fishes. This is the first study to directly compare age and growth for a major fisheries species between east and west populations of a transatlantic reef fish. The main goal of this study was to document age and growth in grey triggerfish Balistes capriscus from coastal waters of Ghana in the Gulf of Guinea (GOG) and compare those with the previous growth studies from that region and with the western Atlantic population. A secondary objective of this study was to evaluate the use of otoliths to age triggerfish and to provide a preliminary comparison with spine-derived age estimates. The results obtained from this study provided an updated understanding of the growth and age structure of the eastern B. capriscus population in GOG. The authors documented that shifts in population attributes occurred for B. capriscus after its major decline in abundance. The differences in physical and biotic characteristics of the East and West Atlantic regions and the differences in collection methods of samples make direct comparisons of growth parameters difficult. Nonetheless, overall differences in maximum sizes and ages were apparent; the western Atlantic population had a larger maximum size and older maximum age. The authors also documented that sagittal otoliths can be used to provide age estimates for triggerfish species, and otoliths as an ageing structure had better between-reader precision compared to dorsal spines.

Ir(III) Cyclometalated Complexes Containing Phenylphenanthridine Ligands with Different Substitutions: Effects on the Electrochemiluminescence Properties.

A family of neutral bis-cyclometalated Ir(III) complexes based on phenanthridine (phent) derivates as cyclometalating ligands and picolinate as an ancillary ligand are described. The influence of extended conjugation, rigidity, and hydrophobicity as well as the electronic nature of the substituents were investigated in relation to the photoluminescence, PL, and electrochemiluminescence, ECL, properties. A significant increase of ECL in aqueous media is observed upon extension of the aromatic system or by substituting the phenyl with a dibenzofurane moiety, in compounds 2 and 3, respectively. Under real immunoassay conditions, these complexes achieve up to 4-fold higher ECL efficiency than the commercial ruthenium standard. These values, among the highest reported in the literature under these conditions, confirm the potential of iridium complexes as alternative labels in commercial instruments.

Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia.

Chronic lymphocytic leukaemia (CLL), the most frequent leukaemia in adults in Western countries, is a heterogeneous disease with variable clinical presentation and evolution. Two major molecular subtypes can be distinguished, characterized respectively by a high or low number of somatic hypermutations in the variable region of immunoglobulin genes. The molecular changes leading to the pathogenesis of the disease are still poorly understood. Here we performed whole-genome sequencing of four cases of CLL and identified 46 somatic mutations that potentially affect gene function. Further analysis of these mutations in 363 patients with CLL identified four genes that are recurrently mutated: notch 1 (NOTCH1), exportin 1 (XPO1), myeloid differentiation primary response gene 88 (MYD88) and kelch-like 6 (KLHL6). Mutations in MYD88 and KLHL6 are predominant in cases of CLL with mutated immunoglobulin genes, whereas NOTCH1 and XPO1 mutations are mainly detected in patients with unmutated immunoglobulins. The patterns of somatic mutation, supported by functional and clinical analyses, strongly indicate that the recurrent NOTCH1, MYD88 and XPO1 mutations are oncogenic changes that contribute to the clinical evolution of the disease. To our knowledge, this is the first comprehensive analysis of CLL combining whole-genome sequencing with clinical characteristics and clinical outcomes. It highlights the usefulness of this approach for the identification of clinically relevant mutations in cancer.

Photophysics and Electrochemiluminescence of Bright Cyclometalated Ir(III) Complexes in Aqueous Solutions.

A family of neutral bis-cyclometalated iridium complexes [Ir(C^N)2(LX)] has been investigated as ECL labels under immunoassay conditions. Among them, the complex based on phenylphenanthridine (pphent) as the C^N ligand, exhibits outstanding performance and it is a candidate to substitute the commercially available Ru-based label in diagnostics.

DNA copy number profiling reveals different patterns of chromosomal instability within colorectal cancer according to the age of onset.

Chromosomal instability resulting in copy number alterations is a hallmark of colorectal cancer (CRC). However, few studies have attempted to characterize the chromosomal changes occurring in early-onset CRC in order to compare them with those taking place within the more extensively studied late-onset CRC subset. Our aim was to characterize the genomic profiles of these two groups of colorectal tumors and to compare them to each other. Array comparative genomic hybridization profiling of 146 colorectal tumors (60 early-onset and 86 late-onset) in combination with an unsupervised analysis was used to define common and specific copy number alterations. We found a number of important differences between the chromosomal instability profiles of each age subset. Thus, losses at 1p36, 1p12, 1q21, 9p13, 14q11, 16p13, and 16p12 were significantly more frequent in younger patients, whereas gains at 7q11 and 7q22 were more frequent in older patients. Moreover, the unsupervised analysis stratified the tumors into two clusters, each one of which was enriched in patients from one of the age subsets. Our findings confirm the existence of substantial differences between the chromosomal instability profiles of the two groups which are more important from a qualitative point of view. Further studies are needed to understand the clinicopathological implications of these dissimilarities.

White light-emitting electrochemical cells based on the Langmuir-Blodgett technique.

Light-emitting electrochemical cells (LECs) showing a white emission have been prepared with Langmuir-Blodgett (LB) films of the metallosurfactant bis[2-(2,4-difluorophenyl)pyridine][2-(1-hexadecyl-1H-1,2,3-triazol-4-yl)pyridine]iridium(III) chloride (1), which work with an air-stable Al electrode. They were prepared by depositing a LB film of 1 on top of a layer of poly(N,N'-diphenyl-N,N'-bis(4-hexylphenyl)-[1,1'-biphenyl]-4,4'-diamine (pTPD) spin-coated on indium tin oxide (ITO). The white color of the electroluminescence of the device contrasts with the blue color of the photoluminescence of 1 in solution and within the LB films. Furthermore, the crystal structure of 1 is reported together with the preparation and characterization of the Langmuir monolayers (π-A compression isotherms and Brewster angle microscopy (BAM)) and LB films of 1 (IR, UV-vis and emission spectroscopy, X-ray photoelectron spectroscopy (XPS), specular X-ray reflectivity (SXR), and atomic force microscopy (AFM)).

Reciprocal translocations in myelodysplastic syndromes and chronic myelomonocytic leukemias: review of 5,654 patients with an evaluable karyotype.

The infrequency of translocations in myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemias (CMML) makes their identification and reporting interesting for the recognition of the recurrent ones and the genes involved in these neoplasias. The aims of this study were to identify new translocations associated with MDS and CMML and to establish their frequency in a cohort of 8,016 patients from the Spanish Group of MDS database. The karyotype was evaluable in 5,654 (70%) patients. Among those, 2,014 (36%) had chromosomal abnormalities, including 213 (10%) translocations identified in 195 patients. The translocations were balanced in 183 (86%) cases and unbalanced in 30 (14%) cases. All chromosomes were found to be involved in translocations, with the single exception of the Y chromosome. The chromosomes most frequently involved were in decreasing frequency: 3, 1, 7, 2, 11, 5, 12, 6, and 17. Translocations were found in karyotypes as the unique chromosomal abnormality (33%), associated with another chromosomal abnormality (11%), as a part of a complex karyotype (17%), and as a part of a monosomal karyotype (38%). There were 155 translocations not previously described in MDS or CMML and nine of them appeared to be recurrent.

Puzzling parrotfishes: Radiocarbon age validation and updated longevity estimates for western Atlantic species in support of sustainable fisheries management.

For management efforts to succeed in Caribbean fisheries, local fishers must support and be willing to comply with fishing regulations. This is more likely when fishers are included in a stock assessment process that utilizes robust scientific evidence, collected in collaboration with fishers, to evaluate the health of fish stocks. Caribbean parrotfishes are important contributors to coral reef ecosystem health while also contributing to local fisheries. Scientifically robust stock assessments require regional species-specific information on age-based key life history parameters, derived from fish age estimates. Evaluation of the accuracy of age estimation methods for fish species is a critical initial step in managing species for long-term sustainable harvest. The current study resulted from a collaborative research program between fish biologists and local fishers investigating age, growth, and reproductive biology of the seven parrotfish species landed in U.S. Caribbean fisheries; specifically, we validated age estimation for stoplight parrotfish Sparisoma viride and queen parrotfish Scarus vetula. This is the first study to directly validate age estimation for any parrotfish species through analysis of Δ14C from eye lens cores. Our age estimation validation results show that enumeration of opaque zones from thin sections of sagittal otoliths for a Sparisoma and a Scarus species provides accurate age estimates. The oldest stoplight parrotfish and queen parrotfish in the Δ14C age estimation validation series were 14 y and 16 y; while the oldest stoplight parrotfish and queen parrotfish we aged to-date using the Δ14C validated age estimation method were 20 y and 21 y, respectively. Fish longevity (maximum age attained/life span) is a key life history parameter used for estimation of natural mortality, survivorship, and lifetime reproductive output. Past reviews on parrotfishes from the Pacific and Atlantic concluded that most Caribbean/western Atlantic parrotfish species are relatively short-lived with estimated maximum ages ranging from 3-9 y. However, information from our collaborative research in the U.S. Caribbean combined with recently published age estimates for Brazilian parrotfish species indicate that many western Atlantic parrotfishes are relatively long-lived with several species attaining maximum ages in excess of 20 y.

Response to lenalidomide in myelodysplastic syndromes with del(5q): influence of cytogenetics and mutations.

Lenalidomide is an effective drug in low-risk myelodysplastic syndromes (MDS) with isolated del(5q), although not all patients respond. Studies have suggested a role for TP53 mutations and karyotype complexity in disease progression and outcome. In order to assess the impact of complex karyotypes on treatment response and disease progression in 52 lenalidomide-treated patients with del(5q) MDS, conventional G-banding cytogenetics (CC), single nucleotide polymorphism array (SNP-A), and genomic sequencing methods were used. SNP-A analysis (with control sample, lymphocytes CD3+, in 30 cases) revealed 5q losses in all cases. Other recurrent abnormalities were infrequent and were not associated with lenalidomide responsiveness. Low karyotype complexity (by CC) and a high baseline platelet count (>280 × 10(9) /l) were associated with the achievement of haematological response (P = 0·020, P = 0·013 respectively). Unmutated TP53 status showed a tendency for haematological response (P = 0·061). Complete cytogenetic response was not observed in any of the mutated TP53 cases. By multivariate analysis, the most important predictor for lenalidomide treatment failure was a platelet count <280 × 10(9) /l (Odds Ratio = 6·17, P = 0·040). This study reveals the importance of a low baseline platelet count, karyotypic complexity and TP53 mutational status for response to lenalidomide treatment. It supports the molecular study of TP53 in MDS patients treated with lenalidomide.

Iridium(III) emitters based on 1,4-disubstituted-1H-1,2,3-triazoles as cyclometalating ligand: synthesis, characterization, and electroluminescent devices.

A series of blue and blue-green emitters based on neutral bis- and tris-cyclometalated Ir(III) complexes with 1-benzyl-4-(2,6-difluorophenyl)-1H-1,2,3-triazole (dfptrBn) as cyclometalating ligand is reported. The bis-cyclometalated complexes of the type [Ir(dfptrBn)(2)(L(^)X)] with different ancillary ligands, L(^)X = picolinate (pic) (2) or 2-(5-(perfluorophenyl)-2H-1,2,4-triazol-3-yl)pyridine (pytrF(5)) (3), are described and their photophysical properties compared with the analogous complexes containing the archetypal 2-(2,4-difluorophenyl)pyridinato (dfppy) as cyclometaled ligand (C(^)N). Complex 2 exhibits a marked solvatochromic behavior, from 475 nm in toluene to 534 nm in formamide, due to the strong MLCT character of its emissive excited state. Complex 3 displays a true-blue emission, narrower in the visible part than FIrpic. In addition, the homoleptic complex [Ir(dfprBn)(3)] (4) and the heteroleptic compounds with mixed arylpyridine/aryltriazole ligands, [Ir(dfptrBn)(2)(C(^)N)] (C(^)N = 2-phenylpyridinato (ppy) (5) or dfppy (6)), have been synthesized and fully characterized. The facial (fac) complex fac-4 is emissive at 77 K showing a deep-blue emission, but it is not luminescent in solution at room temperature similarly to their phenylpyrazole counterparts. However, the fac isomers, fac-5 and fac-6, are highly emissive in solution and thin films, reaching emission quantum yields of 76%, with emission colors in the blue to blue-green region. The photophysical properties for all complexes have been rationalized by means of quantum-chemical calculations. In addition, we constructed electroluminescent devices, organic light-emitting diodes (OLEDs) by sublimation of fac-6, and by solution processed polymer-based devices (PLEDs) using complexes fac-5 or fac-6 as dopants.

Prognostic value of trisomy 8 as a single anomaly and the influence of additional cytogenetic aberrations in primary myelodysplastic syndromes.

Trisomy 8 is the most common chromosomal gain in myelodysplastic syndromes (MDS), however, little is known about the features of MDS with isolated trisomy 8 and the influence of additional cytogenetic aberrations. We determined the characteristics and prognostic factors of 72 patients with trisomy 8 as a single anomaly and analysed also the impact of other aberrations added to trisomy 8 in another 62 patients. According to our study, MDS with isolated trisomy 8 was more frequent in men, with more than one cytopenia in most patients (62%) and having about 4% bone marrow blasts. The multivariate analysis demonstrated that platelet count and percentage bone marrow blasts had the strongest impact on overall survival (OS). The median OS for isolated trisomy 8, trisomy 8 plus one aberration (tr8 + 1), plus two (tr8 + 2) and plus three or more aberrations (tr8 + ≥3) was 34·3, 40, 23·4 and 5·8 months, respectively (P < 0·001). Trisomy 8 confers a poorer prognosis than a normal karyotype in MDS patients with ≥5% bone marrow blasts. This study supports the view that MDS with isolated trisomy 8 should be included in the intermediate cytogenetic risk group.

Integration of global spectral karyotyping, CGH arrays, and expression arrays reveals important genes in the pathogenesis of glioblastoma multiforme.

BACKGROUND: Glioblastoma multiforme (GBM) is the most common primary tumor of the central nervous system in adults. Patients with GBM have few treatment options, and their disease is invariably fatal. Molecularly targeted agents offer the potential to improve patient treatment; however, the use of these will require a fuller understanding of the genetic changes in this complex tumor. METHODS: We analyzed a series of 32 patients with GBM with array comparative genomic hybridization in combination with gene expression analysis. We focused on the recurrent breakpoints found by spectral karyotyping (SKY). RESULTS: By SKY we identified 23 recurrent breakpoints of the 202 translocations found in GBM cases. Gains and losses were identified in chromosomal regions close to the breakpoints by array comparative genomic hybridization. We evaluated the genes located in the regions involved in the breakpoints in depth. A list of 406 genes that showed a level of expression significantly different between patients and control subjects was selected to determine their effect on survival. Genes CACNA2D3, PPP2R2B, SIK, MAST3, PROM1, and PPP6C were significantly associated with shorter survival (median 200 days vs. 450 days, P≤0.03). CONCLUSIONS: We present a list of genes located in regions of breakpoints that could be grounds for future studies to determine whether they are crucial in the pathogenesis of this type of tumor, and we provide a list of six genes associated with the clinical outcome of patients with GBM.

Reversion of epigenetically mediated BIM silencing overcomes chemoresistance in Burkitt lymphoma.

In Burkitt lymphoma/leukemia (BL), achievement of complete remission with first-line chemotherapy remains a challenging issue, as most patients who respond remain disease-free, whereas those refractory have few options of being rescued with salvage therapies. The mechanisms underlying BL chemoresistance and how it can be circumvented remain undetermined. We previously reported the frequent inactivation of the proapoptotic BIM gene in B-cell lymphomas. Here we show that BIM epigenetic silencing by concurrent promoter hypermethylation and deacetylation occurs frequently in primary BL samples and BL-derived cell lines. Remarkably, patients with BL with hypermethylated BIM presented lower complete remission rate (24% vs 79%; P = .002) and shorter overall survival (P = .007) than those with BIM-expressing lymphomas, indicating that BIM transcriptional repression may mediate tumor chemoresistance. Accordingly, by combining in vitro and in vivo studies of human BL-xenografts grown in immunodeficient RAG2(-/-)γc(-/-) mice and of murine B220(+)IgM(+) B-cell lymphomas generated in Eµ-MYC and Eµ-MYC-BIM(+/-) transgenes, we demonstrate that lymphoma chemoresistance is dictated by BIM gene dosage and is reversible on BIM reactivation by genetic manipulation or after treatment with histone-deacetylase inhibitors. We suggest that the combination of histone-deacetylase inhibitors and high-dose chemotherapy may overcome chemoresistance, achieve durable remission, and improve survival of patients with BL.

Expression of VAV1 in the tumour microenvironment of glioblastoma multiforme.

Even though much progress has been made towards understanding the molecular nature of glioma, the survival rates of patients affected by this tumour have not changed significantly over recent years. Better knowledge of this malignancy is still needed in order to predict its outcome and improve patient treatment. VAV1 is an GDP/GTP exchange factor for Rho/Rac proteins with oncogenic potential that is involved in the regulation of cytoskeletal dynamics and cell migration. Here we report its overexpression in 59 patients diagnosed with high-grade glioma, and the associated upregulation of a number of genes coding for proteins also involved in cell invasion- and migration-related processes. Unexpectedly, immunohistochemical experiments revealed that VAV1 is not expressed in glioma cells. Instead, VAV1 is found in non-tumoural astrocyte-like cells that are located either peritumouraly or perivascularly. We propose that the expression of VAV1 is linked to synergistic signalling cross-talk between cancer and infiltrating cells. Interestingly, we show that the pattern of expression of VAV1 could have a role in the neoplastic process in glioblastoma tumours.

Queen triggerfish Balistes vetula: Validation of otolith-based age, growth, and longevity estimates via application of bomb radiocarbon.

Ensuring the accuracy of age estimation in fisheries science through validation is an essential step in managing species for long-term sustainable harvest. The current study used Δ14 C in direct validation of age estimation for queen triggerfish Balistes vetula and conclusively documented that triggerfish sagittal otoliths provide more accurate and precise age estimates relative to dorsal spines. Caribbean fish samples (n = 2045) ranged in size from 67-473 mm fork length (FL); 23 fish from waters of the southeastern U.S. (SEUS) Atlantic coast ranged in size from 355-525 mm FL. Otolith-based age estimates from Caribbean fish range from 0-23 y, dorsal spine-based age estimates ranged from 1-14 y. Otolith-based age estimates for fish from the SEUS ranged from 8-40 y. Growth function estimates from otoliths in the current study (L∞ = 444, K = 0.13, t0 = -1.12) differed from spined-derived estimates in the literature. Our work indicates that previously reported maximum ages for Balistes species based on spine-derived age estimates may underestimate longevity of these species since queen triggerfish otolith-based ageing extended maximum known age for the species by nearly three-fold (14 y from spines versus 40 y from otoliths). Future research seeking to document age and growth population parameters of Balistes species should strongly consider incorporating otolith-based ageing in the research design.

Control of the mutual arrangement of cyclometalated ligands in cationic iridium(III) complexes. Synthesis, spectroscopy, and electroluminescence of the different isomers.

Synthetic control of the mutual arrangement of the cyclometalated ligands (C^N) in Ir(III) dimers, [Ir(C^N)(2)Cl](2), and cationic bis-cyclometalated Ir(III) complexes, [Ir(C^N)(2)(L^L)](+) (L^L = neutral ligand), is described for the first time. Using 1-benzyl-4-(2,4-difluorophenyl)-1H-1,2,3-triazole (HdfptrBz) as a cyclometalating ligand, two different Ir(III) dimers, [Ir(dfptrBz)(2)Cl](2), are synthesized depending on the reaction conditions. At 80 °C, the dimer with an unusual mutual cis-C,C and cis-N,N configuration of the C^N ligands is isolated. In contrast, at higher temperature (140 °C), the geometrical isomer with the common cis-C,C and trans-N,N arrangement of the C^N ligand is obtained. In both cases, an asymmetric bridge, formed by a chloro ligand and two adjacent nitrogens of the triazole ring of one of the cyclometalated ligands, is observed. The dimers are cleaved in coordinating solvents to give the solvento complexes [Ir(dfptrBz)(2)Cl(S)] (S = DMSO or acetonitrile), which maintain the C^N arrangement of the parent dimers. Controlling the C^N ligand arrangement in the dimers allows for the preparation of the first example of geometrical isomers of a cationic bis-cyclometalated Ir(III) complex. Thus, N,N-trans-[Ir(dfptrBz)(2)(dmbpy)](+) (dmbpy = 4,4'-dimethyl-2,2'-bipyridine), with cis-C,C and trans-N,N arrangement of the C^N ligands, as well as N,N-cis-[Ir(dfptrBz)(2)(dmbpy)](+), with cis-C,C and cis-N,N C^N ligand orientation, are synthesized and characterized. Interestingly, both isomers show significantly different photophysical and electroluminescent properties, depending on the mutual arrangement of the C^N ligands. Furthermore, quantum chemical calculations give insight into the observed photophysical experimental data.

Microarray-based classifiers and prognosis models identify subgroups with distinct clinical outcomes and high risk of AML transformation of myelodysplastic syndrome.

The diagnosis of myelodysplastic syndrome (MDS) currently relies primarily on the morphologic assessment of the patient's bone marrow and peripheral blood cells. Moreover, prognostic scoring systems rely on observer-dependent assessments of blast percentage and dysplasia. Gene expression profiling could enhance current diagnostic and prognostic systems by providing a set of standardized, objective gene signatures. Within the Microarray Innovations in LEukemia study, a diagnostic classification model was investigated to distinguish the distinct subclasses of pediatric and adult leukemia, as well as MDS. Overall, the accuracy of the diagnostic classification model for subtyping leukemia was approximately 93%, but this was not reflected for the MDS samples giving only approximately 50% accuracy. Discordant samples of MDS were classified either into acute myeloid leukemia (AML) or "none-of-the-targets" (neither leukemia nor MDS) categories. To clarify the discordant results, all submitted 174 MDS samples were externally reviewed, although this did not improve the molecular classification results. However, a significant correlation was noted between the AML and "none-of-the-targets" categories and prognosis, leading to a prognostic classification model to predict for time-dependent probability of leukemic transformation. The prognostic classification model accurately discriminated patients with a rapid transformation to AML within 18 months from those with more indolent disease.

Upregulation of Dicer is more frequent in monoclonal gammopathies of undetermined significance than in multiple myeloma patients and is associated with longer survival in symptomatic myeloma patients.

Dicer and Drosha are key enzymes in the miRNA-processing pathway which is altered in many human cancers. We analyzed Dicer and Drosha expression levels by quantitative PCR in 151 patients with monoclonal gammopathies: 102 symptomatic myeloma patients, 23 smoldering myelomas and 26 monoclonal gammopathy of undetermined significance. We found that Dicer expression values were significantly higher in monoclonal gammopathy of undetermined significance than in smoldering myelomas and symptomatic myeloma (mean ± SD, 0.84 ± 0.36 vs. 0.60 ± 0.23 and 0.62 ± 0.51; P<0.01). Moreover, the median progression-free survival was significantly longer in symptomatic myeloma patients with high expression of Dicer (not reached vs. 23.6 months; P=0.02). By contrast, no differences in the expression of Drosha among these groups of patients were observed. Our data suggest that Dicer expression may play an important role in the progression and prognosis of monoclonal gammopathies.

Radiocarbon in otoliths of tropical marine fishes: Reference Δ14C chronology for north Caribbean waters.

Reef fishes support important fisheries throughout the Caribbean, but a combination of factors in the tropics makes otolith microstructure difficult to interpret for age estimation. Therefore, validation of ageing methods, via application of Δ14C is a major research priority. Utilizing known-age otolith material from north Caribbean fishes, we determined that a distinct regional Δ14C chronology exists, differing from coral-based chronologies compiled for ageing validation from a wide-ranging area of the Atlantic and from an otolith-based chronology from the Gulf of Mexico. Our north Caribbean Δ14C chronology established a decline series with narrow prediction intervals that proved successful in ageing validation of three economically important reef fish species. In examining why our north Caribbean Δ14C chronology differed from some of the coral-based Δ14C data reported from the region, we determined differences among study objectives and research design impact Δ14C temporal relationships. This resulted in establishing the first of three important considerations relevant to applying Δ14C chronologies for ageing validation: 1) evaluation of the applicability of original goal/objectives and study design of potential Δ14C reference studies. Next, we determined differences between our Δ14C chronology and those from Florida and the Gulf of Mexico were explained by differences in regional patterns of oceanic upwelling, resulting in the second consideration for future validation work: 2) evaluation of the applicability of Δ14C reference data to the region/location where fish samples were obtained. Lastly, we emphasize the application of our north Caribbean Δ14C chronology should be limited to ageing validation studies of fishes from this region known to inhabit shallow water coral habitat as juveniles. Thus, we note the final consideration to strengthen findings of future age validation studies: 3) use of Δ14C analysis for age validation should be limited to species whose juvenile habitat is known to reflect the regional Δ14C reference chronology.