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SummaryAntibody-secreting cells (ASCs) are key contributors to humoral immunity through immunoglobulin production and the potential to be long-lived. ASCs have been recently identified in the thymus (THY) which is of interest as autoreactive THY B cells regulate T cell tolerance. Here, we showed that the young female THY was skewed towards higher production of ASCs relative to males. However, these differences disappeared with age. Intravenous labeling combined with blockade of CD154(CD40L) suggested that THY ASCs were generatedin situin a T cell dependent fashion. Single cell RNA-sequencing revealed that THY ASCs possessed a transcriptional signature indicative of interferon signaling and activation. Flow cytometry confirmed that THY ASCs had increased levels of Toll-like receptor 7 as well as the activation markers CD69 and major histocompatibility class II. Overall, THY ASCs are a unique population that require further investigation to fully appreciate their biological significance.

The authors aim to develop siRNA therapeutics for cancer that can be administered systemically to target tumors and retard their growth. The efficacy of systemic delivery of siRNA to tumors with nanoparticles based on lipids or polymers is often compromised by their rapid clearance from the circulation by the liver. Here, multifunctional cationic and anionic siRNA nanoparticle formulations are described, termed receptor-targeted nanocomplexes (RTNs), that comprise peptides for siRNA packaging into nanoparticles and receptor-mediated cell uptake, together with lipids that confer nanoparticles with stealth properties to enhance stability in the circulation, and fusogenic properties to enhance endosomal release within the cell. Intravenous administration of RTNs in mice leads to predominant accumulation in xenograft tumors, with very little detected in the liver, lung, or spleen. Although non-targeted RTNs also enter the tumor, cell uptake appears to be RGD peptide-dependent indicating integrin-mediated uptake. RTNs with siRNA against

Mutagenic purine-pyrimidine repeats can adopt the left-handed Z-DNA conformation. DNA breaks at potential Z-DNA sites can lead to somatic mutations in cancer or to germline mutations that are transmitted to the next generation. It is not known whether any mechanism exists in the germ line to control Z-DNA structure and DNA breaks at purine-pyrimidine repeats. Here we provide genetic, epigenomic and biochemical evidence for the existence of a biological process that erases Z-DNA specifically in germ cells of the mouse male foetus. We show that a previously uncharacterized zinc finger protein, ZBTB43, binds to and removes Z-DNA, preventing the formation of DNA double-strand breaks. By removing Z-DNA, ZBTB43 also promotes de novo DNA methylation at CG-containing purine-pyrimidine repeats in prospermatogonia. Therefore, the genomic and epigenomic integrity of the species is safeguarded by remodelling DNA structure in the mammalian germ line during a critical window of germline epigenome reprogramming.

Chiococca alba (L.) Hitchc. (snowberry), a member of the Rubiaceae, has been used as a folk remedy for a range of health issues including inflammation and rheumatism and produces a wealth of specialized metabolites including terpenes, alkaloids, and flavonoids. We generated a 558 Mb draft genome assembly for snowberry which encodes 28,707 high-confidence genes. Comparative analyses with other angiosperm genomes revealed enrichment in snowberry of lineage-specific genes involved in specialized metabolism. Synteny between snowberry and Coffea canephora Pierre ex A. Froehner (coffee) was evident, including the chromosomal region encoding caffeine biosynthesis in coffee, albeit syntelogs of N-methyltransferase were absent in snowberry. A total of 27 putative terpene synthase genes were identified, including 10 that encode diterpene synthases. Functional validation of a subset of putative terpene synthases revealed that combinations of diterpene synthases yielded access to products of both general and specialized metabolism. Specifically, we identified plausible intermediates in the biosynthesis of merilactone and ribenone, structurally unique antimicrobial diterpene natural products. Access to the C. alba genome will enable additional characterization of biosynthetic pathways responsible for health-promoting compounds in this medicinal species.

The planar Hall sensitivity of obliquely deposited NiFe(10)/Pt(tPt) /IrMn(8)/Pt(3) (nm) trilayer structures has been investigated by introducing interfacial modification and altering sensor geometry. The peak-to-peak PHE voltage and AMR ratio of the sensors exhibit an oscillatory increase as a function of Pt thickness. This behaviour was attributed to the strong electron spin-orbit scattering at the NiFe/Pt interface of the trilayers. The temperature-dependent PHE signal profiles reveal that the Pt-inserted PHE sensors are stable even at 390 K with a high signal-to-noise ratio and an increased sensitivity due to reduction of exchange bias. In order to further increase the sensitivity, we have fabricated PHE sensors for a fixed Pt thickness of 8 {\AA} by using sensor architectures of a cross, tilted-cross, one-ring and five-ring junctions. We have obtained a sensitivity of 3.82 {\mu}V/Oe.mA for the cross junction, while it considerably increased to 298.5 {\mu}V/Oe.mA for five-ring sensor geometry. The real-time voltage profile of the PHE sensors demonstrate that the sensor states are very stable under various magnetic fields and sensor output voltages turn back to their initial offset values. This provides a great potential for the NiFe/Pt/IrMn-based planar Hall sensors in many sensing applications., Comment: 12 pages, 7 figures

Switchgrass ( is a perennial native North American grass present in two ecotypes: upland, found primarily in the northern range of switchgrass habitats, and lowland, found largely in the southern reaches of switchgrass habitats. Previous studies focused on a diversity panel of primarily northern switchgrass, so to expand our knowledge of genetic diversity in a broader set of North American switchgrass, exome capture sequence data were generated for 632 additional, primarily lowland individuals. In total, over 37 million single nucleotide polymorphisms (SNPs) were identified and a set of 1.9 million high-confidence SNPs were obtained from 1169 individuals from 140 populations (67 upland, 65 lowland, 8 admixed) were used in downstream analyses of genetic diversity and population structure. Seven separate population groups were identified with moderate genetic differentiation [mean fixation index (Fst) estimate of 0.06] between the lowland and the upland populations. Ecotype-specific and population-specific SNPs were identified for use in germplasm evaluations. Relative to rice ( L.), maize ( L.), soybean [ (L.) Merr.], and Gaertn., analyses of nucleotide diversity revealed a high degree of genetic diversity (0.0135) across all individuals, consistent with the outcrossing mode of reproduction and the polyploidy of switchgrass. This study supports the hypothesis that repeated glaciation events, ploidy barriers, and restricted gene flow caused by flowering time differences have resulted in distinct gene pools across ecotypes and geographic regions. These data provide a resource to associate alleles with traits of interest for forage, restoration, and biofuel feedstock efforts in switchgrass.

An overview of the results of the search for small solar transient events, in association with muon enhancements (deficits) registered at ground-level by the Tupi muon telescopes, is presented. Among the events, there are three interplanetary shocks and two solar flares of small scale whose X-ray emission flux is much smaller than 10 − 5 W m−2 at 1 AU (GOES-Tupi connection). Two of the interplanetary shocks are cataloged as corotating interaction region and the third shock is due to the passage of a CME (coronal mass ejection) ejecta (ACE and SOHO-Tupi connection) in the Earth’s proximities. In most cases, the particles excess (deficit) coming from these events have only been observed with spacecraft instruments. However, the Tupi telescopes are located at sea level and within the South Atlantic Anomaly (SAA), a region where the shielding effect of the magnetosphere is not perfectly spherical and shows a ‘dip’. This fact enables the muon telescopes to achieve a low rigidity of response to primary and secondary charged particles (≥ 0.1 GV). Muon excesses (deficits) with significances above 4σ have been found. These events observed at ground admit a temporal correlation with solar transient events observed by spacecrafts, which suggests strongly a real connection between them. Details of these observations are reported.

Introduction: Hash functions are computer algorithms that protect information and secure transactions. In response to the NIST`s "International Call for Hash Function", we developed a biological hash function using the computing capabilities of bacteria. We designed a DNA-based XOR logic gate that allows bacterial colonies arranged in a series on an agar plate to perform hash function calculations. Results and Discussion: In order to provide each colony with adequate time to process inputs and perform XOR logic, we designed and successfully demonstrated a system for time-delayed bacterial growth. Our system is based on the diffusion of -lactamase, resulting in destruction of ampicillin. Our DNA-based XOR logic gate design is based on the op-position of two promoters. Our results showed that and functioned as expected individually, but did not behave as expected in the XOR construct. Our data showed that, contrary to literature reports, the promoter is bidirectional. In the absence of the 3OC6 inducer, the LuxR activator can bind to the promoter and induce backwards transcription. Conclusion and Prospects: Our system of time delayed bacterial growth allows for the successive processing of a bacterial hash function, and is expected to have utility in other synthetic biology applications. While testing our DNA-based XOR logic gate, we uncovered a novel function of . In the absence of autoinducer 3OC6, LuxR binds to and activates backwards transcription. This result advances basic research and has important implications for the widespread use of the promoter.

Sweet potato (Ipomoea batatas [L.] Lam.) is an important subsistence crop in Sub‐Saharan Africa, yet as for many crops, yield can be severely impacted by drought stress. Understanding the genetic mechanisms that control drought tolerance can facilitate the development of drought‐tolerant sweet potato cultivars. Here, we report an expression profiling study using the US‐bred cultivar, Beauregard, and a Ugandan landrace, Tanzania, treated with polyethylene glycol (PEG) to simulate drought and sampled at 24 and 48 hr after stress. At each time‐point, between 4,000 to 6,000 genes in leaf tissue were differentially expressed in each cultivar. Approximately half of these differentially expressed genes were common between the two cultivars and were enriched for Gene Ontology terms associated with drought response. Three hundred orthologs of drought tolerance genes reported in model species were identified in the Ipomoea trifida reference genome, of which 122 were differentially expressed under at least one experimental condition, constituting a list of drought tolerance candidate genes. A subset of genes was differentially regulated between Beauregard and Tanzania, representing genotype‐specific responses to drought stress. The data analyzed and reported here provide a resource for geneticists and breeders toward identifying and utilizing drought tolerance genes in sweet potato.

The Escherichia coli lac Operon is controlled by a regulatory system that has been the subject of intensive study for the past fifty years. The system creates metabolic efficiency by responding to the levels of environmental lactose. In the absence of lactose, the LacI protein acts as a repressor of transcription from the lac promoter. Transcription begins when lactose binds to LacI, which results in the expression of three genes involved in lactose uptake and catabolism. The lac promoter is the most commonly used promoter in the field of synthetic biology. Although it is widely used, the lac promoter is known to have leaky transcription, meaning that transcription takes place even when the repressor is present and the inducer is absent. In an effort to redesign the lac promoter, we tested pLac variants that were reported to have a higher affinity for RNA polymerase than the wild-type. We also compared three mutants of the LacI repressor that were reported to have increasing affinity for the pLa...

Introduction: Sonographic measurement of lateral parapharyngeal wall (LPW) thickness was found to be associated with severity of obstructive sleep apnoea (OSA) in an adult study. (Liu, K.H. et al. Sleep 2007; 30:1503-8) Whether it is independently associated with severity of OSA in paediatric population has not been investigated. Aims: To investigate the association between LPW thickness and obstructive apnoea hypopnoea index (OAHI) in children. We hypothesised that LPW thickness is associated with obstructive apnoea hypopnoea index (OAHI) in multivariate model adjusted for other correlates. Methods: This is a cross-sectional study. Children aged between 6 and 18 years who attended our sleep disorder clinic with symptoms suggestive of OSA were invited to participate. Children with no OSA symptoms were also recruited from aconcurrent population-based epidemiological study. All subjects underwent anthropometric measurements, nocturnal polysomnography, lateral x-ray cephalometry, tonsil size estimation and sonographic measurement of LPW thickness. Results: A total of 129 children [mean (SD) age = 10.2 (2.4), 72 boys] were included in the analysis. Their OAHI ranged from 0 to 46.9/h with a median (IQR) of 0.8 (0.2 to 3.9). Multivariate linear regression analysis revealed that larger tonsils ( p p p Conclusion: LPW thickness may be an independent risk factor for childhood OSA.

Nicotine and its derivatives, by binding to nicotinic acetylcholine receptors ( nAChRs) on bronchial epithelial cells, can regulate cellular signaling and inflammatory processes. Delineation of nAChR subtypes and their responses to nicotine stimulation in bronchial epithelium may provide information for therapeutic targeting in smoking-related inflammation in the airway. Expression of nAChR subunit genes in 60 bronchial epithelial biopsies and immunohistochemical staining for the subcellular locations of nAChR subunit expression were evaluated. Seven human bronchial epithelial cell lines (HBECs) were exposed to nicotine in vitro for their response in nAChR subunit gene expression to nicotine exposure and removal. The relative normalized amount of expression of nAChR α4, α5, and α7 and immunohistochemical staining intensity of nAChR α4, α5, and β3 expression showed significant correlation with lung function parameters. Nicotine stimulation in HBECs resulted in transient increase in the levels of nAChR α5 and α6 but more sustained increase in nAChR α7 expression. nAChR expression in bronchial epithelium was found to correlate with lung function. Nicotine exposure in HBECs resulted in both short and longer term responses in nAChR subunit gene expression. These results gave insight into the potential of targeting nAChRs for therapy in smoking-related inflammation in the airway.

Ethnopharmacological relevance Many herbal topical formulations have been marketed worldwide to prevent hair loss or promote hair growth. Certain in vivo studies have shown promising results among them; however, the effectiveness of their bioactive constituents remains unknown. Aim of the study Recently, prostaglandin D2 (PGD2) inhibition has been discovered as a pharmacological mechanism for treating androgenic alopecia (AGA). This present study was aimed to identify prostaglandin D2 synthase (PTGDS) inhibitors in traditional Chinese medicines (TCMs) for treating AGA. Materials and methods In this study, 389 constituents of 12 selected herbs were docked into 6 different crystal structures of PTGDS. The accuracy of the docking methods was successfully validated with experimental data from the ZINC In Man (Zim) database using receiver operating characteristic (ROC) studies. Seven essential drug properties were predicted for topical formulation: skin permeability, sensitisation, irritation, corrosion, mutagenicity, tumorigenicity and reproductive effects. Results Many constituents of the twelve herbs were found to have more advanced binding energies than the experimentally proved PTGDS inhibitors, but many of them were indicative of at least one type of skin adverse reactions, and exhibited poor skin permeability. Conclusions Overall, ricinoleic acid, acteoside, amentoflavone, quercetin-3-O-rutinoside and hinokiflavone were predicted to be PTGDS inhibitors with good pharmacokinetic properties and minimal adverse skin reactions. These compounds have the highest potential for further in vitro and in vivo investigation with the aim of developing safe and high-efficacy hair loss treatment.

An association between functional polymorphisms of genes resulting in decreased detoxification of carcinogens or DNA repair and aberrant promoter methylation is an attractive hypothesis in lung carcinogenesis. The genotypes at polymorphic sites of the glutathione S-transferase ( GST ) M1 (null/wildtype) and P1 (nucleotide 2627 A/G), myeloperoxidase ( MPO ) (nucleotide −463 G/A), X-ray repair cross-complementing group 1 ( XRCC1 ) (nucleotides 26304 C/T; 28152 G/A), and NADPH quinine oxidoreductase ( NQO1 ) (nucleotide 609 C/T) genes in 75 Chinese patients with non-small cell lung cancer (NSCLC) were characterized with polymerase chain reaction–restriction fragment length polymorphism. Results were correlated with aberrant methylation of the CDKN2A (alias p16 INK4A ), retinoic acid receptor beta ( RARB ), methylguanine-DNA methyltransferase ( MGMT ), and death-associated-protein ( DAP ) kinase genes in the tumors. In comparison with an age-matched control, none of the polymorphisms were associated with increased lung cancer risks. In male patients, however, the MPO −463 GG homozygous state was associated with CDKN2A (alias p16 INK4A ) methylation (odds ratio OR=3.63, 95% confidence interval CI=1.26–10.51), and the XRCC1 26304 T allele in the heterozygous/homozygous state was associated with methylation of CDKN2A (OR=6.13, 95% CI=1.55–24.16) and RARB (OR=7.67, 95% CI=1.62–36.18). In female patients, the GSTP1 G allele in the heterozygous/homozygous state was associated with RARB methylation (OR=18.0, 95% CI=0.76–427.29). These results showed that functional deficiencies in metabolic pathways that protect cells from carcinogen induced DNA damage might be linked to aberrant promoter methylation of the CDKN2A and RARB genes during lung carcinogenesis.

In this paper, we propose a novel layout of cameras atop a moving robot to obtain its ego-motion. In particular, we use three cameras in perpendicular setting. This layout offers a better opportunity e.g. compared to collinear settings for studying the trade-off between the accuracy of features to track and a larger field of view. We show by real experiments and synthetic data alike that using the three cameras as a triple is more advantageous when the fields of view of the cameras are slowly changing. In this case, the triple not only provide more accurate features to track but lead also to a more accurate estimation for their 3D construction. On the contrary, for pure rotations, the fields of view are rapidly changing which offers the advantage to dealing with the three cameras as two stereo pairs with a larger field of view. The extended Kalman filter (EKF) is our real-time estimator of the robot pose.