The olfactory systems of insects are fundamental to all aspects of their behaviour, and insect olfactory receptor neurons (ORNs) exhibit exquisite specificity and sensitivity to a wide range of ...environmental cues. In Drosophila melanogaster, ORN responses are determined by three different receptor families, the odorant (Or), ionotropic-like (IR) and gustatory (Gr) receptors. However, the precise mechanisms of signalling by these different receptor families are not fully understood. Here we report the unexpected finding that the type 4 P-type ATPase phospholipid transporter dATP8B, the homologue of a protein associated with intrahepatic cholestasis and hearing loss in humans, is crucial for Drosophila olfactory responses. Mutations in dATP8B severely attenuate sensitivity of odorant detection specifically in Or-expressing ORNs, but do not affect responses mediated by IR or Gr receptors. Accordingly, we find dATP8B to be expressed in ORNs and localised to the dendritic membrane of the olfactory neurons where signal transduction occurs. Localisation of Or proteins to the dendrites is unaffected in dATP8B mutants, as is dendrite morphology, suggesting instead that dATP8B is critical for Or signalling. As dATP8B is a member of the phospholipid flippase family of ATPases, which function to determine asymmetry in phospholipid composition between the outer and inner leaflets of plasma membranes, our findings suggest a requirement for phospholipid asymmetry in the signalling of a specific family of chemoreceptor proteins.
•Design of Experiments approach for the optimization of SPE-IPS-GC factors.•Automated derivatization for GC-MS/MS analysis of pharmaceutical residues.•The expanded uncertainty (1.28–32.96%) was ...calculated for SPE-IPS-GC-MS/MS.
Measurement uncertainty (MU) is associated with analytical methods; it enhances the confidence of the method and helps in improving the quality of the analytical results. The present study aims to estimate MU of an analytical method used for analyzing the pharmaceutical residues in river water by using solid-phase extraction (SPE) followed by auto injector port silylation coupled with gas chromatography-tandem mass spectrometry (IPS-GC-MS/MS) system. The SPE conditions were optimized by using design of experiments approach (Plackett-Burman Design and Central Composite Design); top-down and bottom-up approaches were used for the estimation of MU. The calibration curves of all pharmaceutical residues showed dynamic linearity in the concentration range of 10–2000 ng/L with coefficient of determination (R2) ranging between 0.985 and 0.999. The limit of detection, limit of quantification, and recovery were found to be in the range of 2.52–7.31 ng/L, 8.33–24.12 ng/L and 81.82–114.14%, respectively. The method robustness was found within acceptation limit (<15% RSD) for system suitability. The expanded uncertainty was estimated in the range of 1.28–32.96% for the SPE method. Precision and recovery were identified as major uncertainty sources of SPE-IPS-GC-MS/MS method for the analysis of pharmaceutical residues in river water.
We undertook this prospective study to compare amino acid metabolism, glucose metabolism, and proliferation in primary and recurrent low grade gliomas using positron emission tomography ...(PET)/computed tomography with F-18 FDOPA, F-18 FDG, and F-18 FLT.
Fifteen patients with newly diagnosed or previously treated low grade gliomas (WHO grade I or II) were subjected to F-18-FDOPA, F-18 FDG, and F-18 FLT PET/computed tomography studies on consecutive days. This included 2 patients in remission as control subjects. Uptake of all the 3 tracers were analyzed visually and quantified using standardized uptake values and tumor to normal (T/N) ratios. The accuracy of all the 3 PET tracers in the detection of newly diagnosed and recurrent low grade gliomas was compared.
F-18 FDOPA was positive in all cases of primary and recurrent low grade gliomas and negative in the patients in remission. Tumor was visualized on F-18 FDG in 7 of 13 cases, F-18-FLT was positive in 4 of 13 cases. Average tumor standardized uptake values max for F-18 FDOPA (5.75 +/- 4.9) and F-18 FLT (1.8 +/- 0.91) was lower than that of F-18 FDG (8.5 +/- 4.4). T/N ratios for F-18-FDOPA (2.3 +/- 0.51) and F-18 FLT (1.8 +/- 0.91) were higher than F-18 FDG (1.03 +/- 0.64) providing good image contrast for tumor detection in positive cases.
F-18 FDOPA scan is superior to both F-18 FLT and F-18 FDG for visualization of primary and recurrent low grade gliomas. F-18-FLT should not be considered for evaluation of recurrent low grade gliomas.
Context. In about 2000, the south pole of Triton experienced an extreme summer solstice that occurs every ∼650 years, when the subsolar latitude reached about 50°S. Bracketing this epoch, a few ...occultations probed the Triton atmosphere in 1989, 1995, 1997, 2008, and 2017. A recent ground-based stellar occultation observed on 6 October 2022 provides a new measurement of the atmospheric pressure on Triton. This is presented here. Aims. The goal is to constrain the volatile transport models (VTMs) of the Triton atmosphere. The atmosphere is basically in vapor pressure equilibrium with the nitrogen ice at its surface. Methods. Fits to the occultation light curves yield the atmospheric pressure of Triton at the reference radius 1400 km, from which the surface pressure is deduced. Results. The fits provide a pressure p 1400 = 1.211 ± 0.039 μbar at radius 1400 km (47 km altitude), from which a surface pressure of p surf = 14.54 ± 0.47 μbar is deduced (1 σ error bars). To within the error bars, this is identical to the pressure derived from the previous occultation of 5 October 2017, p 1400 = 1.18 ± 0.03 μbar and p surf = 14.1 ± 0.4 μbar, respectively. Based on recent models of the volatile cycles of Triton, the overall evolution of the surface pressure over the last 30 years is consistent with N 2 condensation taking place in the northern hemisphere. However, models typically predict a steady decrease in the surface pressure for the period 2005-2060, which is not confirmed by this observation. Complex surface-atmosphere interactions, such as ice albedo runaway and formation of local N 2 frosts in the equatorial regions of Triton, could explain the relatively constant pressure between 2017 and 2022.
It has been evidenced that very few systematic reviews have examined the effectiveness of ginger for pain duration and its severity among women with primary dysmenorrhea. This meta-analysis was ...therefore performed to methodically incorporate and significantly evaluate randomized controlled ginger studies for the treatment of primary dysmenorrhea. The literature was searched using PubMed, Embase, Ovid, ClinicalKey, Medline, and electronic database. We have analyzed clinical trials by comparing ginger with placebo and non-steroidal anti-inflammatory drugs in women with primary dysmenorrhea. The primary outcomes assessed in our meta-analysis were pain severity and pain duration. Secondary outcomes were change in bleeding, side effects of the drug, and rate of satisfaction. We have screened a total of 638 studies, out of which narrative synthesis was formulated for eight studies. We have performed a meta-analysis of five trials examining ginger with placebo and other two randomized controlled trials comparing ginger with a non-steroidal anti-inflammatory drug (NSAID); it seems to be more helpful for relieving menstrual pain than a placebo (mean difference MD = 2.67, 95% CI = 3.51-1.84, P = 0.0001, I2 = 86%), although it was found that ginger and NSAIDs were equally effective in pain severity (risk ratios RR = 1.15, 95% CI = 0.53-2.52, P = 0.72, I2 =77%). We have not observed any significant difference between ginger and placebo on pain duration among primary dysmenorrheic women (MD = -2.22, 95% CI = -7.62-3.18, P = 0.42, I2
= 56%). Accessible information proposes that oral ginger can be a compelling treatment for primary dysmenorrhea. This meta-analysis strongly supports the requirement for high methodological quality consistency for upcoming trials.
Despite the success of vaccines against some microbial pathogens, their utility in the prevention and treatment of cancer has thus far been limited. We have previously demonstrated that vaccination ...with dendritic cells activated with the TLR-4 ligand LPS and IFN-γ promotes an antigen-specific anti-tumor response that prevents tumor recurrence. To evaluate this mechanistically, we here studied the effects of this TLR-activated DC on regulatory T cell activity. Dendritic cells activated with LPS and IFN- γ negated the effects of regulatory T cells on responder cell proliferation. Restoration of responder cell proliferation was noted when TLR-activated dendritic cells were separated from both regulators and responders by a semi-permeable membrane. The effect is therefore mediated by a soluble factor but was independent of both IL-6 and IL-12. Furthermore, the soluble mediator appeared to act at least in part on the regulators themselves rather than responder cells exclusively. Because recent studies have demonstrated conversion of T regulatory cells into IL-17-producing effectors, we further questioned whether the TLR-activated dendritic cell would induce cytokine production and effector function in our system. We found that regulators produced a substantial amount of IFN- γ in the presence of TLR-activated dendritic cells but not immature dendritic cells. IFN-γ production was associated with upregulation of the Th1 transcriptional regulator T-bet, and a significant fraction of IFN-γ-producing regulators coexpressed T-bet and FoxP3. While the effects of the LPS-activated dendritic cell on responder cell proliferation were IL-12 independent, upregulation of T-bet was inhibited by a neutralizing anti-IL-12 antibody. Collectively, these and prior data suggest that varying innate immune signals may direct the phenotype of the immune response in part by inhibiting suppressor T cells and promoting differentiation of these regulators into particular subsets of effectors.
Abstract Objective To assess ovarian reserve in infertile women with genital tuberculosis planning to undergo in vitro fertilization and in women of proven fertility, and compare the findings. ...Methods A cross-sectional study was conducted at an outpatient gynecology unit with 104 women with genital tuberculosis and 104 healthy controls. In each group, ovarian reserve tests consisted in estimating serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and inhibin B on day 3 of a natural menstrual cycle. On the same day ovarian volume, number of antral follicles, and ovarian stromal blood flow were also estimated. Results The mean FSH and LH levels were significantly higher, and the mean inhibin B levels were significantly lower, among the participants with genital tuberculosis than among the controls. Conversely, the mean ovarian volume and the mean number of antral follicles were significantly lower among the participants with genital tuberculosis, as were the mean peak systolic velocity and pulsatility index for each ovary. Conclusion There is no single absolute predictor of ovarian reserve, but combining the current assessment methods provides a close estimation of a woman's reproductive capability. Values for the studied markers showed that ovarian reserve was compromised in women with genital tuberculosis.
Whole-genome sequencing of the protozoan pathogen Trypanosoma cruzi revealed that the diploid genome contains a predicted 22,570 proteins encoded by genes, of which 12,570 represent allelic pairs. ...Over 50% of the genome consists of repeated sequences, such as retrotransposons and genes for large families of surface molecules, which include trans-sialidases, mucins, gp63s, and a large novel family (>1300 copies) of mucin-associated surface protein (MASP) genes. Analyses of the T. cruzi, T. brucei, and Leishmania major (Tritryp) genomes imply differences from other eukaryotes in DNA repair and initiation of replication and reflect their unusual mitochondrial DNA. Although the Tritryp lack several classes of signaling molecules, their kinomes contain a large and diverse set of protein kinases and phosphatases; their size and diversity imply previously unknown interactions and regulatory processes, which may be targets for intervention.
Twenty-seven patients with HER-2/neu overexpressing ductal carcinoma in situ of the breast were enrolled in a neoadjuvant immunization trial for safety and immunogenicity of DC1-polarized dendritic ...cells (DC1) pulsed with 6 HER-2/neu promiscuous major histocompatibility complex class II-binding peptides and 2 additional human leukocyte antigen (HLA)-A2.1 class I-binding peptides. DC1 were generated with interferon-γ and a special clinical-grade bacterial endotoxin (lipopolysaccharide) and administered directly into groin lymph nodes 4 times at weekly intervals before scheduled surgical resection of ductal carcinoma in situ. Patients were monitored for the induction of new or enhanced antipeptide reactivity by interferon-γ ELISPOT and enzyme-linked immunosorbentassays performed on Th cells obtained from peripheral blood or excised sentinel lymph nodes. Responses by cytotoxic T lymphocyte against HLA-A2.1-binding peptides were measured using peptide-pulsed T2 target cells or HER-2/neu-expressing or nonexpressing tumor cell lines. DC1 showed surface phenotype indistinct from "gold standard" inflammatory cocktail-activated DC, but displayed a number of distinguishing functional characteristics including the secretion of soluble factors and enhanced "killer DC" capacity against tumor cells in vitro. Postimmunization, we observed sensitization of Th cells to at least 1 class II peptide in 22 of 25 (88%; 95% exact confidence interval, 68.8%-97.5%) evaluable patients, whereas 11 of 13 (84.6%; 95% exact confidence interval, 64%-99.8%) HLA-A2.1 patients were successfully sensitized to class I peptides. Perhaps most importantly, anti-HER-2/neu peptide responses were observed up to 52-month postimmunization. These data show that even in the presence of early breast cancer such DC1 are potent inducers of durable type I-polarized immunity, suggesting potential clinical value for development of cancer immunotherapy.
Percutaneous renal biopsy (PRB) can result in serious complications. The study is aimed to compare the biopsy yield and complications rate of the real-time ultrasonagram (USG)-guided PRB and needle ...tracking with and without needle guide in two different study periods.
We compared the yield and complications of 2138 kidney biopsies performed in two different periods, 1510 biopsies during the first period from April 2004-December 2010 and 628 biopsies during second period from January 2011-March 2013. All biopsies in both periods were performed by nephrologists. Radiologists provided the real-time image without needle guide during the first period while nephrologists performed both imaging and biopsy with needle guide during the second period.
Of all the 2138 patients, 226 (10.5%) patients developed 118 minor and 108 major complications. Only 13 (2.1%) major complications occurred in the second period and 95 (6.7%) in the first period (P < 0.001). The relative risk of developing a major complication without guide was 3.04 times greater than that of the biopsies performed with use of the guide. The mean number of glomeruli per biopsy obtained during the second period (17.98 ± 6.75) was significantly greater than that of the first period (14.14 ± 6.01) (P = 0.004). The number of passes to acquire adequate tissue (P = 0.001) and percentage of cortex on biopsy (P = 0.001) were also significantly better in the second period. The optimal observation period post biopsy is 24 h.
Real-time USG imaging supported by needle guide device is associated with better biopsy yield and fewer complications.
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