To test whether Zika virus has adapted for more efficient transmission by Aedes aegypti mosquitoes, leading to recent urban outbreaks, we fed mosquitoes from Brazil, the Dominican Republic, and the ...United States artificial blood meals containing 1 of 3 Zika virus strains (Senegal, Cambodia, Mexico) and monitored infection, dissemination, and virus in saliva. Contrary to our hypothesis, Cambodia and Mexica strains were less infectious than the Senegal strain. Only mosquitoes from the Dominican Republic transmitted the Cambodia and Mexica strains. However, blood meals from viremic mice were more infectious than artificial blood meals of comparable doses; the Cambodia strain was not transmitted by mosquitoes from Brazil after artificial blood meals, whereas 61% transmission occurred after a murine blood meal (saliva titers up to 4 log
infectious units/collection). Although regional origins of vector populations and virus strain influence transmission efficiency, Ae. aegypti mosquitoes appear to be competent vectors of Zika virus in several regions of the Americas.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Despite a number of studies on hypnosis as analgesia and anesthesia in several medical conditions, case studies on patients with multiple chemical sensitivity (MCS) are still relatively few. This ...case study is about a female patient with MCS who underwent dental removal using hypnosis as the sole anesthesia. The paradigm in which we work is psychosocial genomics of clinical hypnosis. We used the mind-body transformations therapy, one of the clinical methods of the psychosocial genomics paradigm. In order to induce not only effective analgesia and anesthesia but also a condition of well-being, problem-solving, effective coping and self-empowerment in our patient, 3 different hypnotic protocols were used in a multidimensional approach. Although further research is needed, our work might open up new scenarios for the application of hypnosis as sole anesthesia in conditions such as MCS.
The prevalence of obesity, an established risk factor for many chronic diseases, including several types of cancer, has risen steadily over the past four decades in the United States and worldwide. ...To date, research in this area has focused on the epidemiologic associations between obesity and cancer risk, as well as on the mechanisms underlying those associations. However, an emerging but understudied issue of clinical importance is the diminution of chemotherapeutic efficacy in obese cancer patients. The mechanisms underlying the negative impact of obesity on therapeutic responses are likely multifactorial. The effects of obesity on chemotherapy drug pharmacokinetics and dosage have been extensively reviewed elsewhere, so this review will focus on the interplay among obesity, increased inflammation, metabolic perturbations, and chemoresistance. The ultimate goal of this review is to delineate areas for future research that could lead to the identification of new targets and strategies for improved cancer outcomes in obese patients.
Clinical Pharmacology & Therapeutics (2014); 96 4, 458–463. doi:10.1038/clpt.2014.136
We have developed genetically modified Ae. aegypti mosquitoes that activate the conserved antiviral JAK/STAT pathway in the fat body tissue, by overexpressing either the receptor Dome or the Janus ...kinase Hop by the blood feeding-induced vitellogenin (Vg) promoter. Transgene expression inhibits infection with several dengue virus (DENV) serotypes in the midgut as well as systemically and in the salivary glands. The impact of the transgenes Dome and Hop on mosquito longevity was minimal, but it resulted in a compromised fecundity when compared to wild-type mosquitoes. Overexpression of Dome and Hop resulted in profound transcriptome regulation in the fat body tissue as well as the midgut tissue, pinpointing several expression signatures that reflect mechanisms of DENV restriction. Our transcriptome studies and reverse genetic analyses suggested that enrichment of DENV restriction factor and depletion of DENV host factor transcripts likely accounts for the DENV inhibition, and they allowed us to identify novel factors that modulate infection. Interestingly, the fat body-specific activation of the JAK/STAT pathway did not result in any enhanced resistance to Zika virus (ZIKV) or chikungunya virus (CHIKV) infection, thereby indicating a possible specialization of the pathway's antiviral role.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Stem cell identity and plasticity are controlled by master regulatory genes and complex circuits also involving non-coding RNAs. Circular RNAs (circRNAs) are a class of RNAs generated from ...protein-coding genes by backsplicing, resulting in stable RNA structures devoid of free 5' and 3' ends. Little is known of the mechanisms of action of circRNAs, let alone in stem cell biology. In this study, for the first time, we determined that a circRNA controls mesenchymal stem cell (MSC) identity and differentiation. High-throughput MSC expression profiling from different tissues revealed a large number of expressed circRNAs. Among those, circFOXP1 was enriched in MSCs compared to differentiated mesodermal derivatives. Silencing of circFOXP1 dramatically impaired MSC differentiation in culture and in vivo. Furthermore, we demonstrated a direct interaction between circFOXP1 and miR-17-3p/miR-127-5p, which results in the modulation of non-canonical Wnt and EGFR pathways. Finally, we addressed the interplay between canonical and non-canonical Wnt pathways. Reprogramming to pluripotency of MSCs reduced circFOXP1 and non-canonical Wnt, whereas canonical Wnt was boosted. The opposing effect was observed during generation of MSCs from human pluripotent stem cells. Our results provide unprecedented evidence for a regulatory role for circFOXP1 as a gatekeeper of pivotal stem cell molecular networks.
Altered control of T follicular helper (Tfh) cells can lead to generation of autoantibodies and autoimmune manifestations. Signaling pathways that selectively limit pathogenic responses without ...affecting the protective function of Tfh cells are unknown. Here we show that the ATP-gated ionotropic P2X7 receptor restricts the expansion of aberrant Tfh cells and the generation of self-reactive antibodies in experimental murine lupus, but its activity is dispensable for the expansion of antigen-specific Tfh cells during vaccination. P2X7 stimulation promotes caspase-mediated pyroptosis of Tfh cells and controls the development of pathogenic ICOS
IFN-γ-secreting cells. Circulating Tfh cells from patients with systemic lupus erythematosus (SLE) but not primary antiphospholipid syndrome (PAPS), a nonlupus systemic autoimmune disease, were hyporesponsive to P2X7 stimulation and resistant to P2X7-mediated inhibition of cytokine-driven expansion. These data point to the P2X7 receptor as a checkpoint regulator of Tfh cells; thus, restoring P2X7 activity in SLE patients could selectively limit the progressive amplification of pathogenic autoantibodies, which deteriorate patients' conditions.
Background
Published treatment technique comparisons for postoperative left-sided whole breast irradiation (WBI) with deep-inspiration breath-hold (DIBH) are scarce, small, and inconclusive. In this ...study, fully automated multi-criterial plan optimization, generating a single high-quality, Pareto-optimal plan per patient and treatment technique, was used to compare for a large patient cohort 1) intensity modulated radiotherapy (IMRT) with two tangential fields and 2) volumetric modulated arc therapy (VMAT) with two small tangential subarcs.
Materials and methods
Forty-eight randomly selected patients recently treated with DIBH and 16 × 2.66 Gy were included. The optimizer was configured for the clinical planning protocol. Comparisons between IMRT and VMAT included dosimetric plan parameters, estimated excess relative risks (ERR) for toxicities, delivery times, MUs, and deliverability accuracy at a linac.
Results
The automatically generated IMRT and VMAT plans applied in this study were similar or higher in quality than the manually generated clinical plans. For equal PTVin V95% (98.4 ± 0.9%), VMAT had significant advantages compared to IMRT regarding breast dose homogeneity and doses in heart and ipsilateral lung, at the cost of some minor deteriorations for contralateral breast (few cases with larger deteriorations) and lung. Conformality improved from 1.38 to 1.18 (
p
< 0.001). With VMAT, ERR for major coronary events and ipsilateral lung tumors were reduced by 3% (range: −1–12%) and 16% (range: −3–38%), respectively. MUs and delivery times were higher for VMAT. There were no statistical differences in γ passing rates.
Conclusion
For WBI in conservative therapy of left-sided breast patients treated with DIBH, VMAT with two tangential subarcs was generally dosimetrically superior to IMRT with two tangential static fields. Results need confirmation by robustness analyses.
A yearlong field experimental campaign was conducted to reveal time scales over which antibiotic fluxes vary in the influent of a wastewater treatment plant (WTP). In particular, sampling was carried ...out to ascertain the amplitudes of monthly, daily and hourly fluctuations of several antibiotics. A total of 180 samples was collected at the entrance of a WTP in Lausanne, Switzerland. Sample concentrations were multiplied by flow rate to obtain monthly, daily and hourly mass fluxes of six antibiotics (trimethoprim, norfloxacin, ciprofloxacin, ofloxacin, clindamycin and metronidazole). Seasonality in mass fluxes was observed for all substances, with maximum values in winter being up to an order of magnitude higher than in summer. The hourly measurements of the mass flux of antibiotics were found to have a period of 12h. This was due to peaks in toilet use in the morning and early evening. In particular, the morning peak in flushing coincided with high concentrations (and hence high mass fluxes) due to overnight accumulation of substances in urine. However, little variation was observed in the average daily flux. Consequently, fluctuations in mass fluxes of antibiotics were mainly evident at the monthly and hourly time scales, with little variation on the day–week time scale. These results can aid in optimizing removal strategies and future sampling campaigns focused on antibiotics in wastewater.
Understanding the link between Zika virus (ZIKV) infection and microcephaly requires in vivo models of ZIKV infection in pregnant adults and fetuses. Three studies recently generated such mouse ...models of ZIKV infection, which corroborate previous in vitro evidence linking ZIKV infection and apoptosis induction in neurons and progenitors to microcephaly.
Understanding the link between Zika virus (ZIKV) infection and microcephaly requires in vivo models of ZIKV infection in pregnant adults and fetuses. Three studies recently generated such mouse models of ZIKV infection, which corroborate previous in vitro evidence linking ZIKV infection and apoptosis induction in neurons and progenitors to microcephaly.
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