Transferrin receptor 2-alpha supports cell growth both in iron-chelated cultured cells and in vivo

In most cells, transferrin receptor (TfR1)-mediated endocytosis is a major pathway for cellular iron uptake. We recently cloned the human transferrin receptor 2 (TfR2) gene, which encodes a second receptor for transferrin (Kawabata, H., Yang, R., Hirama, T., Vuong, P. T., Kawano, S., Gombart, A. F., and Koeffler, H. P. (1999) J. Biol. Chem. 274, 20826-20832). In the present study, the regulation of TfR2 expression and function was investigated. A select Chinese hamster ovary (CHO)-TRVb cell line that does not express either TfR1 or TfR2 was stably transfected with either TfR1 or TfR2-alpha cDNA. TfR2-alpha-expressing cells had considerably lower affinity for holotransferrin when compared with TfR1-expressing CHO cells. Interestingly, in contrast to TfR1, expression of TfR2 mRNA in K562 cells was not up-regulated by desferrioxamine (DFO), a cell membrane-permeable iron chelator. In MG63 cells, expression of TfR2 mRNA was regulated in the cell cycle with the highest expression in late G(1) phase and no expression in G(0)/G(1). DFO reduced cell proliferation and DNA synthesis of CHO-TRVb control cells, whereas it had little effect on TfR2-alpha-expressing CHO cells when measured by clonogenic and cell cycle analysis. In addition, CHO cells that express TfR2-alpha developed into tumors in nude mice whereas CHO control cells did not. In conclusion, TfR2 expression may be regulated by the cell cycle rather than cellular iron status and may support cell growth both in vitro and in vivo.     

Water status and growth phenology of a Saharan shrub in north Africa

An experimental study of the relationship between the phenological phases, water relations and climatic conditions was conducted on one shrub species, Spartidium saharae, in Saharan ecosystem of southern Tunisia. The results show that the water potential remained significantly higher than that recorded in other desert shrubs. However, a relationship between the water potential of S. saharae and precipitation was not evident suggesting that access to permanent ground water may be a factor of this decoupling. Although shoot elongation of the species occurred outside the wet season, water shortage induced a decrease in fruit production.     

The role of the concentration and distribution of water in the complex permittivity of breast fat tissue

The structure of breast tissue is complicated and highly variable and presents a great challenge in the development of physical models that may be used to obtain its effective complex permittivity. Empirical models are commonly used by researchers to fit measured data and extrapolated to higher frequencies. However, these models have not been verified experimentally at higher frequencies. Theoretical models of tissue permittivity to explain the role of water are not available today. This communication is a systematic study of several models to estimate the complex permittivity of breast fat tissue based on volume content and distribution of water in the tissue. These models are implemented in (i) long wavelength, sparse concentration limit; (ii) full wave finite element simulation; and (iii) numerical implementation of dynamic multiple scattering theory. A comparison of the proposed models with experimental data is done at 3.2 GHz. Some of the measurement values are in fair agreement with the modeling. The results of the present study are useful for interpreting the large variability in experimentally measured values of the permittivity of breast fat tissue by taking the distribution of water into account. Bioelectromagnetics 30:669–677, 2009. © 2009 Wiley‐Liss, Inc.     

Usefulness of raw bagasse for oil absorption: A comparison of raw and acylated bagasse and their components

Raw bagasse or sugar cane cellulosic residues were modified using acylation grafting with fatty acid. The capability of the grafted bagasse to absorb oil from aqueous solution was studied and compared with the raw bagasse. It was found that the grafted material was significantly more hydrophobic than the raw bagasse. This grafted bagasse had little affinity for water and good affinity for oil. It was also found that bleaching of raw bagasse did not enhance its oil absorptivity. The grafted raw bagasse would be most suitable for applications where oil is to be removed from an aqueous environment. For oil absorbing applications in the absence of water, the raw bagasse was an excellent material.     

Potent Functional Antibody Responses Elicited by HIV-I DNA Priming and Boosting with Heterologous HIV-1 Recombinant MVA in Healthy Tanzanian Adults

Vaccine-induced HIV antibodies were evaluated in serum samples collected from healthy Tanzanian volunteers participating in a phase I/II placebo-controlled double blind trial using multi-clade, multigene HIV-DNA priming and recombinant modified vaccinia Ankara (HIV-MVA) virus boosting (HIVIS03). The HIV-DNA vaccine contained plasmids expressing HIV-1 gp160 subtypes A, B, C, Rev B, Gag A, B and RTmut B, and the recombinant HIV-MVA boost expressed CRF01_AE HIV-1 Env subtype E and Gag-Pol subtype A. While no neutralizing antibodies were detected using pseudoviruses in the TZM-bl cell assay, this prime-boost vaccination induced neutralizing antibodies in 83% of HIVIS03 vaccinees when a peripheral blood mononuclear cell (PBMC) assay using luciferase reporter-infectious molecular clones (LucR-IMC) was employed. The serum neutralizing activity was significantly (but not completely) reduced upon depletion of natural killer (NK) cells from PBMC (p=0.006), indicating a role for antibody-mediated Fcγ-receptor function. High levels of antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies against CRF01_AE and/or subtype B were subsequently demonstrated in 97% of the sera of vaccinees. The magnitude of ADCC-mediating antibodies against CM235 CRF01_AE IMC-infected cells correlated with neutralizing antibodies against CM235 in the IMC/PBMC assay. In conclusion, HIV-DNA priming, followed by two HIV-MVA boosts elicited potent ADCC responses in a high proportion of Tanzanian vaccinees. Our findings highlight the potential of HIV-DNA prime HIV-MVA boost vaccines for induction of functional antibody responses and suggest this vaccine regimen and ADCC studies as potentially important new avenues in HIV vaccine development.

Trial Registration

Controlled-Trials ISRCTN90053831 The Pan African Clinical Trials Registry ATMR2009040001075080 (currently PACTR2009040001075080)     

A new method for the extraction of fetal ECG from the dependent abdominal signals using blind source separation and adaptive noise cancellation techniques

Background

The electrocardiogram (ECG) is a diagnostic tool that records the electrical activity of the heart, and depicts it as a series of graph-like tracings, or waves. Being able to interpret these details allows diagnosis of a wide range of heart problems. Fetal electrocardiogram (FECG) extraction has an important impact in medical diagnostics during the mother pregnancy period. Since the observed FECG signals are often mixed with the maternal ECG (MECG) and the noise induced by the movement of electrodes or by mother motion, the separation process of the ECG signal sources from the observed data becomes quite complicated. One of its complexity is when the ECG sources are dependent, thus, in this paper we introduce a new approach of blind source separation (BSS) in the noisy context for both independent and dependent ECG signal source. This approach consist in denoising the observed ECG signals using a bilateral total variation (BTV) filter; then minimizing the Kullbak-Leibler divergence between copula densities to separate the FECG signal from the MECG one.

Results

We present simulation results illustrating the performance of our proposed method. We will consider many examples of independent/dependent source component signals. The results will be compared with those of the classical method called independent component analysis (ICA) under the same conditions. The accuracy of source estimation is evaluated through a criterion, called again the signal-to-noise-ratio (SNR). The first experiment shows that our proposed method gives accurate estimation of sources in the standard case of independent components, with performance around 27 dB in term of SNR. In the second experiment, we show the capability of the proposed algorithm to successfully separate two noisy mixtures of dependent source components - with classical criterion devoted to the independent case - fails, and that our method is able to deal with the dependent case with good performance.

Conclusions

In this work, we focus specifically on the separation of the ECG signal sources taken from skin two electrodes located on a pregnant woman’s body. The ECG separation is interpreted as a noisy linear BSS problem with instantaneous mixtures. Firstly, a denoising step is required to reduce the noise due to motion artifacts using a BTV filter as a very effective one-pass filter for denoising. Then, we use the Kullbak-Leibler divergence between copula densities to separate the fetal heart rate from the mother one, for both independent and dependent cases.

     

Variation in Plasmodium falciparum Histidine-Rich Protein 2 (Pfhrp2) and Plasmodium falciparum Histidine-Rich Protein 3 (Pfhrp3) Gene Deletions in Guyana and Suriname

Guyana and Suriname have made important progress in reducing the burden of malaria. While both countries use microscopy as the primary tool for clinical diagnosis, malaria rapid diagnostic tests (RDTs) are useful in remote areas of the interior where laboratory support may be limited or unavailable. Recent reports indicate that histidine-rich protein 2 (PfHRP2)-based diagnostic tests specific for detection of P. falciparum may provide false negative results in some parts of South America due to the emergence of P. falciparum parasites that lack the pfhrp2 gene, and thus produce no PfHRP2 antigen. Pfhrp2 and pfhrp3 genes were amplified in parasite isolates collected from Guyana and Suriname to determine if there were circulating isolates with deletions in these genes. Pfhrp3 deletions were monitored because some monoclonal antibodies utilized in PfHRP2-based RDTs cross-react with the PfHRP3 protein. We found that all 97 isolates from Guyana that met the inclusion criteria were both pfhrp2- and pfhrp3-positive. In Suriname (N = 78), 14% of the samples tested were pfhrp2-negative while 4% were pfhrp3-negative. Furthermore, analysis of the genomic region proximal to pfhrp2 and pfhrp3 revealed that genomic deletions extended to the flanking genes. We also investigated the population substructure of the isolates collected to determine if the parasites that had deletions of pfhrp2 and pfhrp3 belonged to any genetic subtypes. Cluster analysis revealed that there was no predominant P. falciparum population substructure among the isolates from either country, an indication of genetic admixture among the parasite populations. Furthermore, the pfhrp2-deleted parasites from Suriname did not appear to share a single, unique genetic background.