Evaluation of the Reliability of Six Commercial SERS Substrates

Plasmonics - Based on high sensitivity, specific fingerprinting spectra and real-time detection, surface-enhanced Raman spectroscopy (SERS) is a powerful tool for the observation, the detection and...     

Estimating effective population size using RADseq: Effects of SNP selection and sample size

Effective population size (N_e) is a key parameter of population genetics. However, N_e remains challenging to estimate for natural populations as several factors are likely to bias estimates. These factors include sampling design, sequencing method, and data filtering. One issue inherent to the restriction site‐associated DNA sequencing (RADseq) protocol is missing data and SNP selection criteria (e.g., minimum minor allele frequency, number of SNPs). To evaluate the potential impact of SNP selection criteria on N_e estimates (Linkage Disequilibrium method) we used RADseq data for a nonmodel species, the thornback ray. In this data set, the inbreeding coefficient F_IS was positively correlated with the amount of missing data, implying data were missing nonrandomly. The precision of N_eestimates decreased with the number of SNPs. Mean N_e estimates (averaged across 50 random data sets with2000 SNPs) ranged between 237 and 1784. Increasing the percentage of missing data from 25% to 50% increased N_e estimates between 82% and 120%, while increasing the minor allele frequency (MAF) threshold from 0.01 to 0.1 decreased estimates between 71% and 75%. Considering these effects is important when interpreting RADseq data‐derived estimates of effective population size in empirical studies.     

Consolidation par Y-epratuzumab en fractionné dans le lymphome B diffus à grandes cellules : résultats préliminaires d’une étude de phase II

Purpose

A multicenter, non-randomized, on-going phase II study, promoted by the GOELAMS aims to evaluate the efficacy and safety of fractionated administration of ⁹⁰Y-epratuzumab (two injections 7 days apart) in consolidation therapy for patients older than 60 years with diffuse large B-cell lymphoma and large tumor mass who presented a complete response (CR), unconfirmed CR (uCR) or partial response (PR) after induction therapy with six courses of R-CHOP14. We report the preliminary results on 41 of the 75 enrolled patients.

Patients and method

Toxicity was evaluated according to NCI-CTC version 3. The CR and uCR rate and the rate of conversion of PR to CR/uCR 6 weeks after injections of ⁹⁰Y-epratuzumab were evaluated using IWRC criteria.

Results

Thirty-three patients received two injections of ⁹⁰Y-epratuzumab. The toxicity of ⁹⁰Y-epratuzumab was mainly hematologic, characterized by neutropenia grade 3/4 in 81.8% of patients and thrombocytopenia grade 3/4 in 78.8% of patients, reversible. Two patients (6.1%) had grade 3/4 non-hematologic toxicity. Six weeks after injection of ⁹⁰Y-epratuzumab, 40.0% of patients improved their response and the rate of CR/RCu was 83.9%.

Conclusion

These preliminary results show significant toxicity, but mainly hematologic, expected in consolidation. The response rate is encouraging and needs to be confirmed by sufficient number of inclusions and follow-up.     

Plasmodesmatal pores in the torus of bordered pit membranes affect cavitation resistance of conifer xylem

The pit membrane in bordered pits of conifer tracheids is characterized by a porous margo and central thickening (torus), which is traditionally considered to function as an impermeable safety valve against air-seeding. However, electron microscopy based on 33 conifer species, including five families and 19 genera, reveals that pores occur in the torus of 13 of the species studied. The pores have a plasmodesmatal origin with an average diameter of 51 nm and grouped arrangement. Evidence for embolism spreading via pores in tori is supported by the pore sizes, which correspond relatively well with the pressure inducing cavitation. Predictions based on earlier correlations between pit structure and cavitation resistance were only weakly supported for species with punctured tori. Moreover, species with punctured tori are significantly less resistant to cavitation than species with non-punctured tori. Nevertheless, absolute pore diameters must be treated with caution and correlations between theoretical and measured air-seeding pressures are weak. Because most pores appear not to traverse the torus but are limited to one torus pad, only complete pores would trigger air-seeding. Embolism spreading through a leaky torus is not universal across gymnosperms and unlikely to represent the only air-seeding mechanism.     

Pattern of cytokine expression by rat liver epithelial cells supporting long-term culture of human CD34(+)umbilical cord blood cells

Fetal liver is the main site of haematopoiesis during mid-gestation. The adult liver still provides a favourable environment for extramedullary haematopoiesis. Nevertheless, regulation of liver haematopoiesis by cell-cell contacts or by cytokines remains poorly understood. Recently, we have shown that rat liver epithelial cells (RLECs) support long-term survival and multilineage differentiation of adult human CD34(+)and CD34(+)/CD38(-)haematopoietic cells obtained from granulocyte-colony stimulating factor mobilized peripheral blood and from bone marrow respectively. In addition, the importance of physical proximity between haematopoietic cells and RLECs was clearly demonstrated. Here, our findings give evidence that RLECs belonging to the epithelial but non-parenchymal liver compartment also sustain the long-term production of progenitors from human CD34(+)umbilical cord blood cells. Moreover, to better analyse the regulation of haematopoiesis in this RLEC coculture model, we have investigated the cytokine expression by RLECs alone and by RLECs coming from coculture with CD34(+)cells from umbilical cord blood. We demonstrated that a broad spectrum of cytokines acting at different stages of haematopoiesis is produced by RLECs. Interestingly, an upregulation of leukemia inhibitory factor expression by RLECs in presence of CD34(+)haematopoietic cells was observed. These data suggest an important role of cell-cell interactions in the regulation of haematopoiesis.     

Influence of salt on the structure of DMPG studied by SAXS and optical microscopy

Aqueous dispersions of 50 mM dimyristoylphosphatidylglycerol (DMPG) in the presence of increasing salt concentrations (2-500 mM NaCl) were studied by small angle X-ray scattering (SAXS) and optical microscopy between 15 and 35 °C. SAXS data show the presence of a broad peak around q ∼ 0.12 Å^− 1 at all temperatures and conditions, arising from the electron density contrasts within the bilayer. Up to 100 mM NaCl, this broad peak is the main feature observed in the gel and fluid phases. At higher ionic strength (250-500 mM NaCl), an incipient lamellar repeat distance around d = 90-100 Å is detected superimposed to the bilayer form factor. The data with high salt were fit and showed that the emergent Bragg peak is due to loose multilamellar structures, with the local order vanishing after ∼ 4d. Optical microscopy revealed that up to 20 mM NaCl, DMPG is arranged in submicroscopic vesicles. Giant (loose) multilamellar vesicles (MLVs) start to appear with 50 mM NaCl, although most lipids are arranged in small vesicles. As the ionic strength increases, more and denser MLVs are seen, up to 500 mM NaCl, when MLVs are the prevailing structure. The DLVO theory could account for the experimentally found interbilayer distances.     

Influence of salt on the structure of DMPG studied by SAXS and optical microscopy

Aqueous dispersions of 50 mM dimyristoylphosphatidylglycerol (DMPG) in the presence of increasing salt concentrations (2-500 mM NaCl) were studied by small angle X-ray scattering (SAXS) and optical microscopy between 15 and 35 degrees C. SAXS data show the presence of a broad peak around q approximately 0.12 A(-1) at all temperatures and conditions, arising from the electron density contrasts within the bilayer. Up to 100 mM NaCl, this broad peak is the main feature observed in the gel and fluid phases. At higher ionic strength (250-500 mM NaCl), an incipient lamellar repeat distance around d=90-100 A is detected superimposed to the bilayer form factor. The data with high salt were fit and showed that the emergent Bragg peak is due to loose multilamellar structures, with the local order vanishing after approximately 4d. Optical microscopy revealed that up to 20 mM NaCl, DMPG is arranged in submicroscopic vesicles. Giant (loose) multilamellar vesicles (MLVs) start to appear with 50 mM NaCl, although most lipids are arranged in small vesicles. As the ionic strength increases, more and denser MLVs are seen, up to 500 mM NaCl, when MLVs are the prevailing structure. The DLVO theory could account for the experimentally found interbilayer distances.     

CD40 ligand protects from TRAIL-induced apoptosis in follicular lymphomas through NF-kappaB activation and up-regulation of c-FLIP and Bcl-xL

The TNF family member TRAIL is emerging as a promising cytotoxic molecule for antitumor therapy. However, its mechanism of action and the possible modulation of its effect by the microenvironment in follicular lymphomas (FL) remain unknown. We show here that TRAIL is cytotoxic only against FL B cells and not against normal B cells, and that DR4 is the main receptor involved in the initiation of the apoptotic cascade. However, the engagement of CD40 by its ligand, mainly expressed on a specific germinal center CD4(+) T cell subpopulation, counteracts TRAIL-induced apoptosis in FL B cells. CD40 induces a rapid RNA and protein up-regulation of c-FLIP and Bcl-x(L). The induction of these antiapoptotic molecules as well as the inhibition of TRAIL-induced apoptosis by CD40 is partially abolished when NF-kappaB activity is inhibited by a selective inhibitor, BAY 117085. Thus, the antiapoptotic signaling of CD40, which interferes with TRAIL-induced apoptosis in FL B cells, involves NF-kappaB-mediated induction of c-FLIP and Bcl-x(L) which can respectively interfere with caspase 8 activation or mitochondrial-mediated apoptosis. These findings suggest that a cotreatment with TRAIL and an inhibitor of NF-kappaB signaling or a blocking anti-CD40 Ab could be of great interest in FL therapy.