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Germline precursors and intermediates of broadly neutralizing antibodies (bNAbs) are essential to the understanding of humoral response to HIV-1 infection and B-cell lineage vaccine design. Using a native-like gp140 trimer probe, ...
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Germline precursors and intermediates of broadly neutralizing antibodies (bNAbs) are essential to the understanding of humoral response to HIV-1 infection and B-cell lineage vaccine design. Using a native-like gp140 trimer probe, we examined antibody libraries constructed from donor-17, the source of glycan-dependent PGT121-class bNAbs recognizing the N332 supersite on the HIV-1 envelope glycoprotein. To facilitate this analysis, a digital panning method was devised that combines biopanning of phage-displayed antibody libraries, 900 bp long-read next-generation sequencing, and heavy/light (H/L)-paired antibodyomics. In addition to single-chain variable fragments resembling the wild-type bNAbs, digital panning identified variants of PGT124 (a member of the PGT121 class) with a unique insertion in the heavy chain complementarity-determining region 1, as well as intermediates of PGT124 exhibiting notable affinity for the native-like trimer and broad HIV-1 neutralization. In a competition assay, these bNAb intermediates could effectively compete with mouse sera induced by a scaffolded BG505 gp140.681 trimer for the N332 supersite. Our study thus reveals previously unrecognized lineage complexity of the PGT121-class bNAbs and provides an array of library-derived bNAb intermediates for evaluation of immunogens containing the N332 supersite. Digital panning may prove to be a valuable tool in future studies of bNAb diversity and lineage development.
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We demonstrate the synthesis of star-shaped poly(ethylene oxide)-block-poly(2-ethyl-2-oxazoline) [PEOm-b-PEtOxn]x block copolymers with eight arms using two different approaches, either the “arm-first” or the “core-first” strategy...
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We demonstrate the synthesis of star-shaped poly(ethylene oxide)-block-poly(2-ethyl-2-oxazoline) [PEOm-b-PEtOxn]x block copolymers with eight arms using two different approaches, either the “arm-first” or the “core-first” strategy. Different lengths of the outer PEtOx blocks ranging from 16 to 75 repeating units were used, and the obtained materials [PEO28-b-PEtOxx]8 were characterized via size exclusion chromatography (SEC), nuclear magnetic resonance spectroscopy (NMR), and Fourier-transform infrared spectroscopy (FT-IR) measurements. First investigations regarding the solution behavior in water as a non-selective solvent revealed significant differences. Whereas materials synthesized via the “core-first” method seemed to be well soluble (unimers), aggregation occurred in the case of materials synthesized by the “arm-first” method using copper-catalyzed azide-alkyne click chemistry.
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Purpose: The purified fraction of Albizia julibrissin saponins (AJSAF) was evaluated and characterized for the adjuvant activity on porcine reproductive and respiratory syndrome virus (PRRSV) vaccine. Methods: The effects of AJSAF...
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Purpose: The purified fraction of Albizia julibrissin saponins (AJSAF) was evaluated and characterized for the adjuvant activity on porcine reproductive and respiratory syndrome virus (PRRSV) vaccine. Methods: The effects of AJSAF on serum PRRSV N protein-specific antibody titers, splenocyte proliferation, natural killer (NK) cell activity, mRNA expression of cytokines and transcription factors, secretion of cytokines, T cells response in splenocytes, as well as delayed type hypersensitivity (DTH) in the mice immunized PRRSV vaccine were determined by ELISA, MTT assay, flow cytometry and quantitative real-time PCR (qRT-PCR). Results: AJSAF not only significantly enhanced the serum PRRSV N protein-specific IgG, IgG1, IgG2a and IgG2b antibody titers in the mice immunized with PRRSV CH-1R modified live vaccine (CH-1R MLV), inactivated vaccine (CH-1R IAV), and highly pathogenic JXA1-R modified live vaccine (JXA1-R MLV), but promoted the concanavalin A (Con A)-, lipopolysaccharide (LPS)- and PRRSV N protein-stimulated splenocyte proliferation, the activities of NK cells and delayed type hypersensitivity (DTH) in the mice immunized CH-1R MLV. AJSAF also remarkably induced the production of both Th1 (IFN-γ) and Th2 (IL-10) cytokines, and up-regulated the mRNA expression levels of Th1 cytokines (IFN-γ and IL-2) and transcription factors (T-bet and STAT4) as well as Th2 cytokines (IL-4 and IL-10) and transcription factors (GATA-3 and STAT6) in splenocytes from the CH-1R MLV-immunized mice. Furthermore, AJSAF markedly increased the frequencies of PRRSV N protein-specific Th1 (INF-γ + and IL-2 + ) and Th2 (IL-4+ and IL-10 + ) CD4 T cells as well as Tc1 (INF-γ + and IL-2 + ) and Tc2 (IL-4 + and IL-10 + ) CD8 T cells in splenocytes from the CH-1R MLV-immunized mice. Conclusions: Our results demonstrated that AJSAF had a potential to enhance and improve immune responses and elicit both Th1/Th2 and Tc1/Tc2 response to PRRSV vaccine, and that AJSAF would be a promising adjuvant candidate for PRRSV vaccine.
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Recently, the increasing number of bio-safety assessments on cadmium-containing quantum dots (QDs) suggested that they could lead to detrimental effects on the central nervous system (CNS) of living organisms, but the underlying a...
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Recently, the increasing number of bio-safety assessments on cadmium-containing quantum dots (QDs) suggested that they could lead to detrimental effects on the central nervous system (CNS) of living organisms, but the underlying action mechanisms are still rarely reported. In this study, whole-transcriptome sequencing was performed to analyze the changes in genome-wide gene expression pattern of rat hippocampus after treatments of cadmium telluride (CdTe) QDs with two sizes to understand better the mechanisms of CdTe QDs causing toxic effects in the CNS. We identified 2095 differentially expressed genes (DEGs). Fifty-five DEGs were between the control and 2.2 nm CdTe QDs, 1180 were between the control and 3.5 nm CdTe QDs and 860 were between the two kinds of CdTe QDs. It seemed that the 3.5 nm CdTe QD exposure might elicit severe effects in the rat hippocampus than 2.2 nm CdTe QDs at the transcriptome level. After bioinformatics analysis, we found that most DEG-enriched Gene Ontology subcategories and Kyoto Encyclopedia of Genes and Genomes pathways were related with the immune system process. For example, the Gene Ontology subcategories included immune response, inflammatory response and T-cell proliferation; Kyoto Encyclopedia of Genes and Genomes pathways included NOD/Toll-like receptor signaling pathway, nuclear factor-κB signaling pathway, tumor necrosis factor signaling pathway, natural killer cell-mediated cytotoxicity and T/B-cell receptor signaling pathway. The traditional toxicological examinations confirmed the systemic immune response and CNS inflammation in rats exposed to CdTe QDs. This transcriptome analysis not only revealed the probably molecular mechanisms of CdTe QDs causing neurotoxicity, but also provided references for the further related studies. Copyright ? 2018 John Wiley & Sons, Ltd.
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A cross-sectional study was conducted to observe the growth and feeding practices of infants in Southern China. The study comprised 758 infants at 4 (n = 383) and 8 (n = 375) months of age in Guangzhou City, and 398 infants at 4 m...
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A cross-sectional study was conducted to observe the growth and feeding practices of infants in Southern China. The study comprised 758 infants at 4 (n = 383) and 8 (n = 375) months of age in Guangzhou City, and 398 infants at 4 months of age in the rural areas of Guangdong Province. Anthropometrics and feeding information were obtained. In the city, the mean Z-scores of weight-for-age (WAZ), height-for-age (HAZ) and weight-for-height (WHZ) of the infants were above the National Center for Health Statistics (NCHS) reference median at 4 months. By 8 months, WAZ and WHZ, but not HAZ scores, were below the NCHS reference median (p < 0.05). Rural infants were lighter and shorter than the NCHS reference at 4 months (p < 0,05). Prevalence of breast feeding was 65% at 4 months and 44% at 8 months for urban infants, but 99% of the rural infants were breastfed at 4 months. Rural infants were fed less commercial baby cereals, high-protein foods, and fruits, but more homemade cereals than urban infants. The attained size of the 4 months old urban infants was positively associated with the exposure loads of breast milk, fruits, and vitamin supplements, but negatively associated with formula, rice porridge, and glucose drinks. Body weight of the 4-month rural infants was: negatively associated with the exposure loads of formula and glucose drinks, By 8 months, the growth of the urban infants was associated positively with the exposure loads of fruits, high-protein foods, and vitamins supplements, but negatively with home made cereals and Chinese herbs. Improved feeding practices, including the usage of appropriate weaning and complementary foods, are needed for optimal growth of both urban and rural infants.
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Age-related diseases may result from shared biological mechanisms in intrinsic processes of aging. Genetic effects on age-related diseases are often modulated by environmental factors due to their little contribution to fitness or...
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Age-related diseases may result from shared biological mechanisms in intrinsic processes of aging. Genetic effects on age-related diseases are often modulated by environmental factors due to their little contribution to fitness or are mediated through certain endophenotypes. Identification of genetic variants with pleiotropic effects on both common complex diseases and endophenotypes may reveal potential conflicting evolutionary pressures and deliver new insights into shared genetic contribution to healthspan and lifespan. Here, we performed pleiotropic meta-analyses of genetic variants using five NIH-funded datasets by integrating univariate summary statistics for age-related diseases and endophenotypes. We investigated three groups of traits: (1) endophenotypes such as blood glucose, blood pressure, lipids, hematocrit, and body mass index, (2) time-to-event outcomes such as the age-at-onset of diabetes mellitus (DM), cancer, cardiovascular diseases (CVDs) and neurodegenerative diseases (NDs), and (3) both combined. In addition to replicating previous findings, we identify seven novel genome-wide significant loci (< 5e-08), out of which five are low-frequency variants. Specifically, from Group 2, we find rs7632505 on 3q21.1 in SEMA5B, rs460976 on 21q22.3 (1 kb from TMPRSS2) and rs12420422 on 11q24.1 predominantly associated with a variety of CVDs, rs4905014 in ITPK1 associated with stroke and heart failure, rs7081476 on 10p12.1 in ANKRD26 associated with multiple diseases including DM, CVDs, and NDs. From Group 3, we find rs8082812 on 18p11.22 and rs1869717 on 4q31.3 associated with both endophenotypes and CVDs. Our follow-up analyses show that rs7632505, rs4905014, and rs8082812 have age-dependent effects on coronary heart disease or stroke. Functional annotation suggests that most of these SNPs are within regulatory regions or DNase clusters and in linkage disequilibrium with expression quantitative trait loci, implying their potential regulatory influence on the expression of nearby genes. Our mediation analyses suggest that the effects of some SNPs are mediated by specific endophenotypes. In conclusion, these findings indicate that loci with pleiotropic effects on age-related disorders tend to be enriched in genes involved in underlying mechanisms potentially related to nervous, cardiovascular and immune system functions, stress resistance, inflammation, ion channels and hematopoiesis, supporting the hypothesis of shared pathological role of infection, and inflammation in chronic age-related diseases.
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We address an optimal transmit power allocation problem that minimizes the outage probability of a secondary user (SU) who is allowed to coexist with a primary user (PU) in a narrowband spectrum sharing cognitive radio network, un...
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We address an optimal transmit power allocation problem that minimizes the outage probability of a secondary user (SU) who is allowed to coexist with a primary user (PU) in a narrowband spectrum sharing cognitive radio network, under a long term average transmit power constraint at the secondary transmitter (SU-TX) and an average interference power constraint at the primary receiver (PU-RX), with quantized channel state information (CSI) (including both the channels from SU-TX to SU-RX, denoted as g_1 and the channel from SU-TX to PU-RX, denoted as g_0) at the SU-TX. The optimal quantization regions in the vector channel space is shown to have a "stepwise" structure. With this structure, the above outage minimization problem can be explicitly formulated and solved by employing the Karush-Kuhn-Tucker (KKT) necessary optimality conditions to obtain a locally optimal quantized power codebook. A low-complexity near-optimal quantized power allocation algorithm is derived for the case of large number of feedback bits. More interestingly, we show that as the number of partition regions approaches infinity, the length of interval between any two adjacent quantization thresholds on the g_0 axis is asymptotically equal when the average interference power constraint is active. Similarly, we show that when the average interference power constraint is inactive, the ratio between any two adjacent quantization thresholds on the g_1 axis becomes asymptotically identical. Using these results, an explicit expression for the asymptotic SU outage probability at high rate quantization (as the number of feedback bits goes to infinity) is also provided, and is shown to approximate the optimal outage behavior extremely well for large number of bits of feedback via numerical simulations. Analysis on the extension to multiple secondary users case (cognitive multiple-access network) is also discussed. Numerical results illustrate that with only a few bits of feedback, the derived algorithms - rovide secondary outage performance very close to that with full CSI at the SU-TX.
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L'article précédent présentait un réseau de << sites critiques >> pour la conservation de la biodiversité forestière et des systèmes écologiques du Cameroun, du Gabon et de Guinée équatoriale. Afin de rationaliser le choix des sites à dév...
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L'article précédent présentait un réseau de << sites critiques >> pour la conservation de la biodiversité forestière et des systèmes écologiques du Cameroun, du Gabon et de Guinée équatoriale. Afin de rationaliser le choix des sites à développer et les priorités d'investissement, nous exposons, ici, une méthode d'évaluation des sites en fonction de leur intérêt biologique et des menaces qu'ils subissent. Les résultats de cette évaluation permettent d'entamer un processus itératifde prise de décision et de suivi-évaluation. Malgré une augmentation des pressions sur les ressources forestières, la valeur biologique et écologique du réseau sous-régional de sites critiques reste bonne : il est encore temps d'agir pour préserver ce potentiel naturel et le valoriser de manière durable. Chacun des pays concernés recèle des sites d'importance régionale-voire continentale - pour la conservation de la biodiversité forestière africaine. De par leur importance biologique et leur role dans la survie des forêts, les sites critiques et leur périphérie devraient faire l'objet des premières actions de mise en oeuvre des plans de zonage et d'aménagement sur le terrain.
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This paper presents a frame for classifying polarimetric synthetic aperture radar (PolSAR) data. The frame is based on the combination of wavelet polarization information, textons, and sparse coding. Polarimetric synthesis unites ...
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This paper presents a frame for classifying polarimetric synthetic aperture radar (PolSAR) data. The frame is based on the combination of wavelet polarization information, textons, and sparse coding. Polarimetric synthesis unites with the discrete wavelet frame to obtain wavelet polarization variance through the calculation of the wavelet variance in the space of polarization states. The K-means cluster algorithm is implemented to cluster the wavelet polarization variance vectors of the training samples for the purpose of constructing a texton dictionary. A patch, in which all the wavelet polarization variance vectors match those in the texton dictionary, is used to obtain a statistical histogram. Sparse coding is applied to describe the histogram feature and generate a new texture feature called sparse coding of a wavelet polarization texton. Finally, support vector machine is used for the classification. All experiments are carried out on five sets of PolSAR data. The experimental results confirm that the proposed method effectively classifies PolSAR data.
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The genome of tomato (Solanum lycopersicum L.) is being sequenced by an international consortium of 10 countries (Korea, China, the United Kingdom, India, the Netherlands, France, Japan, Spain, Italy, and the United States) as par...
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The genome of tomato (Solanum lycopersicum L.) is being sequenced by an international consortium of 10 countries (Korea, China, the United Kingdom, India, the Netherlands, France, Japan, Spain, Italy, and the United States) as part of the larger “International Solanaceae Genome Project (SOL): Systems Approach to Diversity and Adaptation” initiative. The tomato genome sequencing project uses an ordered bacterial artificial chromosome (BAC) approach to generate a high-quality tomato euchromatic genome sequence for use as a reference genome for the Solanaceae and euasterids. Sequence is deposited at GenBank and at the SOL Genomics Network (SGN). Currently, there are around 1000 BACs finished or in progress, representing more than a third of the projected euchromatic portion of the genome. An annotation effort is also underway by the International Tomato Annotation Group. The expected number of genes in the euchromatin is ～40,000, based on an estimate from a preliminary annotation of 11% of finished sequence. Here, we present this first snapshot of the emerging tomato genome and its annotation, a short comparison with potato (Solanum tuberosum L.) sequence data, and the tools available for the researchers to exploit this new resource are also presented. In the future, whole-genome shotgun techniques will be combined with the BAC-by-BAC approach to cover the entire tomato genome. The high-quality reference euchromatic tomato sequence is expected to be near completion by 2010.
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