Mapping of the healthy immunoglobulin repertoire over the course of B cell maturation by deep pyrosequencing

Healthy immunoglobulin repertoire has not been extensively evaluated reflecting in part the challenge of generating sufficiently robust data sets by conventional clonal sequencing. Deep sequencing has revolutionized the capacity to evaluate the depth and breadth of the Ig repertoire along the B cell developmental pathway, and can be used to pin point defect(s) of primary or acquired B-cell associated diseases. In this study healthy IgM and IgG repertoires were studied by 454-pyrosequencing to establish the healthy controls for diseased repertoires. (...)

Effects of foliar fertilization of common bean (Phaseolus vulgaris, L.) during the seed-filling stage

An experiment was carried out with common bean (Phaseolus vulgaris, L.) in a Red Yellow Latossol, sandy phase, in order to study the influence of foliar spraying of the Hanway nutrient solution (NPKS) at grain filling stage on: 1) grain yield; 2) the uptake of fertilizer and soil nitrogen by this crop through the root system and 3) the efficiency of utilization of the nitrogen in the foliar spray solution by the grain. The results of this experiment showed that the foliar application of the Hanway solution with ammonium nitrate at the pod filling period caused severe leaf burn and grain yield was inferior to that of the plants which received a soil application of this fertilizer at the same stage. These facts can be attributed to the presence of ammonium nitrate in the concentration used. The composition of final spray was: 114,28 Kg NH4NO3 + 43,11 Kg potassium poliphosphate + 12,44 Kg potassium sulphate per 500 litres. The uptake of nitrogen fertilizer through the root system and the efficiency of its utilization was greater than that through the leaves.

Dinâmica reprodutiva de Oligosarcus jenynsii e O. robustus (Characiformes, Characidae) na lagoa Fortaleza, Rio Grande do Sul, Brasil

Oligosarcus jenynsii (Günther, 1864) and O. robustus Menezes, 1969 are fish species distributed in Rio Grande do Sul, Brazil, Uruguay, and northern Argentina. The reproductive period and recruitment, sex ratio, absolute and relative fecundity, and body length at first gonadal maturation of the two carnivorous species from Fortaleza Lagoon were analized. The specimens were sampled monthly, from May 2000 to April 2001, with fishing effort of 24 hours/month, using stationary gillnets of different mesh sizes and seine net (three samples per edge). The records of each individual included total length, total weight, gonad weight, sex and gonadal maturity stage. The reproductive period of both O. jenynsii and O. robustus ranges from May/June to November/December, according to the bimonthly variation of the mean values of gonosomatic index, and the relative frequencies of the gonadal maturation stages. Recruitment of new individuals to the population occurs from November/December to March/April. The sex ratio is different from 1:1 for O. jenynsii and similar to 1:1 for O. robustus. The mean absolute fecundity, calculated by counting sub-sampled oocytes from mature females, was 14,483 oocytes for O. jenynsii, and 16,308 oocytes for O. robustus. The first maturation curve shows that O. jenynsii begins to reproduce between 84 mm and 104 mm (total length), and O. robustus between 126 mm and 146 mm, probably at similar ages.

Gonad development in females of fiddler crab Uca rapax (Crustacea, Brachyura, Ocypodidae) using macro and microscopic techniques

The morphology of the ovaries in Uca rapax (Smith, 1870) was described based on macroscopic and microscopic analysis. Females were collected in Itamambuca mangrove, Ubatuba, state of São Paulo, Brazil. In the laboratory, 18 females had their ovaries removed and prepared for histology. Each gonad developmental stage was previously determined based on external and macroscopic morphology and afterwards each stage was microscopically described. The ovaries of U. rapax showed a pronounced macroscopic differentiation in size and coloration with the maturation of the gonad, with six ovarian developmental stages: immature, rudimentary, developing, developed, advanced and spent. During the vitellogenesis, the amount of oocytes in secondary stage increases in the ovary, resulting in a change in coloration of the gonad. Oogonias, primary oocytes, secondary oocytes and follicular cells were histologically described and measured. In female’s ovaries of U. rapax the modifications observed in the oocytes during the process of gonad maturation are similar to descriptions of gonads of other females of brachyuran crustaceans. The similarities are specially found in the morphological changes in the reproductive cells, and also in the presence and arrange of follicle cells during the process of ovary maturation. When external morphological characteristics of the gonads were compared to histological descriptions, it was possible to observe modifications that characterize the process in different developmental stages throughout the ovarian cycle and, consequently, the macroscopic classification of gonad stages agree with the modifications of the reproductive cells.

Morphological aspects of cell reabsorption in laying queens and workers of Apis mellifera (Hymenoptera, Apidae)

The occurrence of cell reabsorption in the ovaries of queens in several rates of laying eggs, artificially impeded of laying, and in nurse workers, of Apis mellifera (Linnaeus, 1758), was studied with light (LM) and transmission electron microscopy (TEM). Two types of structures were described and named by analogy with vertebrates ovarian structures, as corpus luteus, when resulting from the reabsorption of the follicular cells after ovulation, and corpus atresicus when resulting from total follicular reabsorption at any oocyte developmental stage. These structures have the same morphological characteristics and physiological signification in both castes. The corpus luteus occurrence indicates ovulation and its number is correspondent to the queen's rates of oviposition. The presence of this structure in nurse workers ovarioles shows that this caste may lay eggs. The incidence of corpus atresicus in queens decay with the increasing of the oviposition indicating that the inhibition of the normal sequence of oocyte maturation in the ovaries is deleterious. Both, corpus luteus and corpus atresicus incidence may be influenced by environmental factors.

Morphology and dynamics of male gametogenesis in Sympterygia bonapartii (Chondrichthyes, Rajidae) from Northern Patagonia

ABSTRACT The smallnose fanskate, Sympterygia bonapartii Müller & Henle, 1841 is one of the most disembarked items in commercial harbors in Argentina. In this work, the microscopic architecture of mature male gonads and the dynamics of cysts development are analyzed as a contribution to awareness of the reproductive biology of the species. Some biological data related to reproduction are given as well. Two seasons were sampled (fall and spring) and length classes's frequency distribution and maturity stages frequency distribution are given. Size at first sexual maturation for males was estimated at 57 cm of total length. Testes are symmetric, peer, lobed, with several germinal zones. Inside the gonads, there are many spermatocysts, containing reproductive cells at the same developmental stage. On the basis of their cytological and microanatomical features, several maturative degrees of the spermatogenic series were differentiated. Few Leydig cells were recognized at the interstitial tissue among cysts. The microscopic and semiquantitative analysis performed in this work provides morphological information about male gametogenesis and some biological data for the North Patagonian population of this economically and ecologically important species.

New FFT/IFFT Factorizations with Regular Interconnection Pattern Stage-to-Stage Subblocks

Les factoritzacions de la FFT (Fast Fourier Transform) que presenten un patró d’interconnexió regular entre factors o etapes son conegudes com algorismes paral·lels, o algorismes de Pease, ja que foren originalment proposats per Pease. En aquesta contribució s’han desenvolupat noves factoritzacions amb blocs que presenten el patró d’interconnexió regular de Pease. S’ha mostrat com aquests blocs poden ser obtinguts a una escala prèviament seleccionada. Les noves factoritzacions per ambdues FFT i IFFT (Inverse FFT) tenen dues classes de factors: uns pocs factors del tipus Cooley-Tukey i els nous factors que proporcionen la mateix patró d’interconnexió de Pease en blocs. Per a una factorització donada, els blocs comparteixen dimensions, el patró d’interconnexió etapa a etapa i a més cada un d’ells pot ser calculat independentment dels altres.

Y-90-Ibritumomab Tiuxetan (Zevalin (R)) Consolidation of First Remission In Advanced-Stage Follicular Non-Hodgkin's Lymphoma: Updated Results After a Median Follow-up of 66.2 Months From the International, Randomized, Phase III First-Line Indolent Trial (FIT) In 414 Patients

The FIT trial was conducted to evaluate the safety and efficacy of 90Y-ibritumomab tiuxetan (0.4 mCi/kg; maximum dose 32 mCi) when used as consolidation of first complete or partial remission in patients with previously untreated, advanced-stage follicular lymphoma (FL). Patients were randomly assigned to either 90Y-ibritumomab treatment (n = 207) or observation (n = 202) within 3 months (mo) of completing initial induction therapy (chemotherapy only: 86%; rituximab in combination with chemotherapy: 14%). Response status prior to randomization did not differ between the groups: 52% complete response (CR)/CR unconfirmed (CRu) to induction therapy and 48% partial response (PR) in the 90Y-ibritumomab arm vs 53% CR/CRu and 44% PR in the control arm. The primary endpoint was progression-free survival (PFS) of the intent-to-treat (ITT) population. Results from the first extended follow-up after a median of 3.5 years revealed a significant improvement in PFS from the time of randomization with 90Y-ibritumomab consolidation compared with control (36.5 vs 13.3 mo, respectively; P < 0.0001; Morschhauser et al. JCO. 2008; 26:5156-5164). Here we report a median follow-up of 66.2 mo (5.5 years). Five-year PFS was 47% in the 90Y-ibritumomab group and 29% in the control group (hazard ratio (HR) = 0.51, 95% CI 0.39-0.65; P < 0.0001). Median PFS in the 90Y-ibritumomab group was 49 mo vs 14 mo in the control group. In patients achieving a CR/CRu after induction, 5-year PFS was 57% in the 90Y-ibritumomab group, and the median had not yet been reached at 92 months, compared with a 43% 5-year PFS in the control group and a median of 31 mo (HR = 0.61, 95% CI 0.42-0.89). For patients in PR after induction, the 5-year PFS was 38% in the 90Y-ibritumomab group with a median PFS of 30 mo vs 14% in the control group with a median PFS of 6 mo (HR = 0.38, 95% CI 0.27-0.53). Patients who had received rituximab as part of induction treatment had a 5-year PFS of 64% in the 90Y-ibritumomab group and 48% in the control group (HR = 0.66, 95% CI 0.30-1.47). For all patients, time to next treatment (as calculated from the date of randomization) differed significantly between both groups; median not reached at 99 mo in the 90Y-ibritumomab group vs 35 mo in the control group (P < 0.0001). The majority of patients received rituximab-containing regimens when treated after progression (63/82 [77%] in the 90Y-ibritumomab group and 102/122 [84%] in the control group). Overall response rate to second-line treatment was 79% in the 90Y-ibritumomab group (57% CR/CRu and 22% PR) vs 78% in the control arm (59% CR/CRu, 19% PR). Five-year overall survival was not significantly different between the groups; 93% and 89% in the 90Y-ibritumomab and control groups, respectively (P = 0.561). To date, 40 patients have died; 18 in the 90Y-ibritumomab group and 22 in the control group. Secondary malignancies were diagnosed in 16 patients in the 90Y-ibritumomab arm vs 9 patients in the control arm (P = 0.19). There were 6 (3%) cases of myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) in the 90Y-ibritumomab arm vs 1 MDS in the control arm (P = 0.063). In conclusion, this extended follow-up of the FIT trial confirms the benefit of 90Y-ibritumomab consolidation with a nearly 3 year advantage in median PFS. A significant 5-year PFS improvement was confirmed for patients with a CR/CRu or a PR after induction. Effective rescue treatment with rituximab-containing regimens may explain the observed no difference in overall survival between both patient groups who were - for the greater part - rituximab-naïve.

Superior outcome of women with stage I/II cutaneous melanoma: pooled analysis of four European Organisation for Research and Treatment of Cancer phase III trials.

PURPOSE: Several studies observed a female advantage in the prognosis of cutaneous melanoma, for which behavioral factors or an underlying biologic mechanism might be responsible. Using complete and reliable follow-up data from four phase III trials of the European Organisation for Research and Treatment of Cancer (EORTC) Melanoma Group, we explored the female advantage across multiple end points and in relation to other important prognostic indicators. PATIENTS AND METHODS: Patients diagnosed with localized melanoma were included in EORTC adjuvant treatment trials 18832, 18871, 18952, and 18961 and randomly assigned during the period of 1984 to 2005. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs for women compared with men, adjusted for age, Breslow thickness, body site, ulceration, performed lymph node dissection, and treatment. RESULTS: A total of 2,672 patients with stage I/II melanoma were included. Women had a highly consistent and independent advantage in overall survival (adjusted HR, 0.70; 95% CI, 0.59 to 0.83), disease-specific survival (adjusted HR, 0.74; 95% CI, 0.62 to 0.88), time to lymph node metastasis (adjusted HR, 0.70; 95% CI, 0.51 to 0.96), and time to distant metastasis (adjusted HR, 0.69; 95% CI, 0.59 to 0.81). Subgroup analysis showed that the female advantage was consistent across all prognostic subgroups (with the possible exception of head and neck melanomas) and in pre- and postmenopausal age groups. CONCLUSION: Women have a consistent and independent relative advantage in all aspects of the progression of localized melanoma of approximately 30%, most likely caused by an underlying biologic sex difference.

First-line chemotherapy with local treatment can prevent external-beam irradiation and enucleation in low-stage intraocular retinoblastoma.

PURPOSE: To evaluate the efficacy of first-line chemotherapy (CT) in preventing external-beam radiotherapy (EBR) and/or enucleation in patients with retinoblastoma (Rbl). PATIENTS AND METHODS: Twenty-four patients with newly diagnosed unilateral or bilateral Rbl received CT associated with local treatment (LT). Two to five courses of etoposide and carboplatin were administered at 3- to 4-week intervals, depending on tumor response, and were completed each time by LT. RESULTS: Tumor response was observed in all eyes. Twenty-one of 24 patients showed a complete response (CR) that persisted at a median follow-up (FU) of 31 months (range, 4 to 41 months). Among the three patients who relapsed, two were lost to FU and one died of progressive disease. CR was achieved by CT and LT alone in 15 (71.4%) of 21 patients with less advanced disease (groups I to III). Six other patients with advanced disease (groups IV and V) experienced treatment failure and needed salvage treatment by EBR and/or enucleation. The difference between the two patient groups with regard to disease stage was statistically significant (P <.0001). EBR could be avoided in 13 (68.4%) of 19 patients, who presented with groups I to III (15 eyes) and group V (one eye) disease, whereas enucleation could be avoided in only two (40%) of five. CONCLUSION: CT combined with intensive LT is effective in patients with groups I to III Rbl, permitting the avoidance of EBR in the majority of these young children and, thus, reducing the risk of long-term sequelae. This is in contrast with the disappointing results for patients with groups IV and V Rbl, in whom EBR and/or enucleation was needed.

Partial Knowledge Restrictions on theTwo-Stage Threshold Model of Choice

In the context of the two-stage threshold model of decision making, with the agent’s choices determined by the interaction Of three “structural variables,” we study the restrictions on behavior that arise when one or more variables are xogenously known. Our results supply necessary and sufficient conditions for consistency with the model for all possible states of partial Knowledge, and for both single- and multivalued choice functions.