Photoreceptor replacement by transplantation is proposed as a treatment for blindness. Transplantation of healthy photoreceptor precursor cells into diseased murine eyes leads to the presence of ...functional photoreceptors within host retinae that express an array of donor-specific proteins. The resulting improvement in visual function was understood to be due to donor cells integrating within host retinae. Here, however, we show that while integration occurs the majority of donor-reporter-labelled cells in the host arises as a result of material transfer between donor and host photoreceptors. Material transfer does not involve permanent donor-host nuclear or cell-cell fusion, or the uptake of free protein or nucleic acid from the extracellular environment. Instead, RNA and/or protein are exchanged between donor and host cells in vivo. These data require a re-evaluation of the mechanisms underlying rescue by photoreceptor transplantation and raise the possibility of material transfer as a strategy for the treatment of retinal disorders.
The mammalian target of rapamycin (mTOR) pathway is deregulated in castration-resistant prostate cancer (CRPC). We investigated the efficacy and toxicity of temsirolimus, an mTOR inhibitor, in ...chemotherapy-naïve CRPC.
In this phase II open label study, eligible patients received IV temsirolimus at 25 mg weekly until objective disease progression, unacceptable toxicity or investigator's discretion. Toxicity was assessed every 4 weeks and responses every 8 weeks. Primary end point was calculating the overall response (OR) rate as well as measuring stable disease (SD) to assess the overall clinical benefit calculated as OR+SD. Secondary end points included prostatic-specific antigen (PSA) changes and time to progression biochemically and radiographically. Correlative studies included prospective assessment of quality of life (QoL) using two previously validated scales.
Although the sponsor halted the study early, 21 patients were enrolled of which, 15 were evaluable for efficacy and OR. Median age was 74 (range: 57-89), median PSA was 237.5 ng ml(-1) (range: 8.2-2360), visceral disease present in 11 patients (52%), and 17 patients (81%) patients had Gleason score (7-10). Two patients had a partial response (PR) and eight had SD. The OR was 13% (2/15) and the overall clinical benefit (OR+SD) was 67% (10/15). Median time to radiographic disease progression was 2 months (range 2-10 months). Biochemical response assessment was available for 14/15 patients. Any PSA decline was observed in four patients (28.5%; 4/14) with one patient (7%) having >50% PSA decline. Median time to progression by PSA was 2 months (range 1-10 months). With a median follow-up of 32 months, median overall survival (OS) was 13 months (range: 2-37) and three patients remain alive at the data cutoff (5/2013) for an OS of 14% at 4 years on an intent-to-treat analysis. Major non-haematologic toxicities included fatigue (19%) and pneumonia (14%). Main laboratory toxicities included hyperglycaemia (24%) and hypophosphatemia (14%). Also, 52% of enrolled patients had serious adverse events. Other toxicities were consistent with previously reported adverse events with temsirolimus. Despite these observed adverse events, temsirolimus did not adversely impact QoL.
Temsirolimus monotherapy has minimal activity in chemotherapy-naïve CRPC.
This study was focused on the analysis of the contents (by HPLC-DAD) and antioxidant activity of phenolic compounds of aquatic higher plant
Callitriche cophocarpa
. The novelty of the work was: 1) ...the study of the species which is almost unknown in the context of investigations of bio-active compounds and, 2) the application of a unique
L
-band electron resonance spectroscopy (
L
-band EPR) to measure antioxidant activity of samples. The results were compared with those obtained for microalgae
Chlorella
and
Spirulina
which are widely distributed as the diet supplements. The obtained results are very promising with respect to the freeze-dried material of
Callitriche
, which revealed both high level of phenolic compounds (33 mg g
−1
dry weight) and antioxidant activity (0.14 g of reduced DPPH· g
−1
dry weight). An isoform of sinapic acid appeared to be the main fraction in this sample. The average content of the total phenolic compounds in
Callitriche
freeze-dried samples was
ca
. 43 or 25 times higher than in the case of the
Chlorella
or
Spirulina
samples, respectively. These samples showed also 16 times lower scavenging activity in relation to freeze-dried
Callitriche
material.
Daytime vision is highly dependent on cone photoreceptors and retinal degenerations resulting in their death are a leading cause of blindness. A promising treatment strategy is the replacement of ...lost cones by cell therapy. Here we characterise cone differentiation in retinae derived from suspension cultures of mouse embryonic stem cells (mESCs). Similar to in vivo development, a temporal pattern of progenitor marker expression is followed by the differentiation of early thyroid hormone receptor β2-positive cone precursors and at later stages of culture, photoreceptors exhibiting cone-specific phototransduction-related proteins. We also established that the Notch pathway limits cone genesis, whilst retinoic acid signalling regulates their maturation comparable to their actions in vivo. Importantly, mESC-derived cones can be isolated in large numbers and transplanted into the adult mouse retina. Following transplantation, these cells show the capacity to survive and express mature markers. Together, this work identifies a robust renewable source of transplantable cone precursors for daylight vision repair studies.
Daytime vision is highly dependent on cone photoreceptors and retinal degenerations resulting in their death are a leading cause of blindness. A promising treatment strategy is the replacement of ...lost cones by cell therapy. Here we characterise cone differentiation in retinae derived from suspension cultures of mouse embryonic stem cells (mESCs). Similar to in vivo development, a temporal pattern of progenitor marker expression is followed by the differentiation of early thyroid hormone receptor β2-positive cone precursors and at later stages of culture, photoreceptors exhibiting cone-specific phototransduction-related proteins. We also established that the Notch pathway limits cone genesis, whilst retinoic acid signalling regulates their maturation comparable to their actions in vivo. Importantly, mESC-derived cones can be isolated in large numbers and transplanted into the adult mouse retina. Following transplantation, these cells show the capacity to survive and express mature markers. Together, this work identifies a robust renewable source of transplantable cone precursors for daylight vision repair studies.
The field experiment was carried out with two methods fertilization applied: broadcasting and in rows simultaneously with grain sowing. The effectiveness of fertilization methods was estimated at ...increasing levels of fertilization, from 17.4 to 56.0 kg P/ha and with application of superphosphate and ammonium phosphate. Fertilization maize of ammonium phosphate and starting fertilization enlarged yields of dry mass stover, in comparison to superphosphate and broadcasting fertilization. Yields of dry mass of ears and whole plants depended on kind of fertilizer and of fertilizing method
Abstract
Far-ultraviolet (FUV) emission lines from dwarf stars are important driving sources of photochemistry in planetary atmospheres. Properly interpreting spectral features of planetary ...atmospheres critically depends on the emission of its host star. While the spectral energy distributions (SEDs) of K- and M-type stars have been extensively characterized by previous observational programs, the full X-ray to infrared SED of F-type stars has not been assembled to support atmospheric modeling. On the second flight of the Suborbital Imaging Spectrograph for Transition-region Irradiance from Nearby Exoplanet host stars (SISTINE-2) rocket-borne spectrograph, we successfully captured the FUV spectrum of Procyon A (F5 IV-V) and made the first simultaneous observation of several emission features across the FUV bandpass (1010–1270 and 1300–1565 Å) of any cool star. We combine flight data with stellar models and archival observations to develop the first SED of a mid-F star. We model the response of a modern Earth-like exoplanet’s upper atmosphere to the heightened X-ray and extreme UV radiation within the habitable zone of Procyon A. These models indicate that this planet would not experience significant atmospheric escape. We simulate observations of the Ly
α
transit signal of this exoplanet with the Hubble Space Telescope (HST) and the Habitable Worlds Observatory (HWO). While marginally detectable with HST, we find that H
i
Ly
α
transits of potentially habitable exoplanets orbiting high radial velocity F-type stars could be observed with HWO for targets up to 150 pc away.
With increasing energy and resource consumption due to population growth, the biorefinery concept is becoming popular. This concept aims to harness all the properties of biomass by producing energy ...and recovering useful chemical products. Nutrients such as nitrogen and phosphorus play a key role in the world’s food production because they are the main elements used in fertilizer production. Hydrothermal carbonization (HTC) has been presented as a suitable option for energy recovery that can also be used as a pre-treatment for enhanced nutrient recovery. During the HTC process, part of the nitrogen and phosphorus are solubilized into the process water and the other part remains within the hydrochar. Hydrochars are mainly used as soil amendments due to their high content of phosphorus and nitrogen, but in this process, water still contains a considerable concentration of these compounds making it a potential source for their recovery. Therefore, HTC may boost the nutrient recovery strategy by extraction (process water) or densification (hydrochar) from biomass if it is coupled with another nutrient recovery process. This review presents an overview of the phosphorus and nitrogen fate during the HTC process from a perspective of nutrient recovery, presenting existing technologies and future trends.
•A critical review of HTC process for N and P recovery strategy is presented.•Different strategies of recovery of P and N using HTC are compared.•Detailed mechanisms of solubilization of P and N during HTC are described.•Reaction pathways involving P and N during HTC are outlined.•Existing technologies for P and N recovery are presented.
Summary
Rearrangement of MYC is associated with a poor prognosis in patients with diffuse large B cell lymphoma (DLBCL) and B cell lymphoma unclassifiable (BCLU), particularly in the setting of ...double hit lymphoma (DHL). However, little is known about outcomes of patients who demonstrate MYC rearrangement without evidence of BCL2 or BCL6 rearrangement (single hit) or amplification (>4 copies) of MYC. We identified 87 patients with single hit lymphoma (SHL), 22 patients with MYC‐amplified lymphoma (MYC amp) as well as 127 DLBCL patients without MYC rearrangement or amplification (MYC normal) and 45 patients with DHL, all treated with either R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or intensive induction therapy. For SHL and MYC amp patients, the 2‐year progression‐free survival rate (PFS) was 49% and 48% and 2‐year overall survival rate (OS) was 59% and 71%, respectively. SHL patients receiving intensive induction experienced higher 2‐year PFS (59% vs. 23%, P = 0·006) but similar 2‐year OS as compared with SHL patients receiving R‐CHOP. SHL DLBCL patients treated with R‐CHOP, but not intensive induction, experienced significantly lower 2‐year PFS and OS (P < 0·001 for both) when compared with MYC normal patients. SHL patients appear to have a poor prognosis, which may be improved with receipt of intensive induction.
Steady consumption of beer results in a steady output of residues, i.e., brewer’s spent grain (BSG). Its valorization, using hydrothermal carbonization (HTC) seems sensible. However, a significant ...knowledge gap regarding the variability of this residue and its influence on the valorization process and its potential use in biorefineries exists. This study attempted to fill this gap by characterization of BSG in conjunction with the main product (beer), taking into accounts details of the brewing process. Moreover, different methods to assess the performance of HTC were investigated. Overall, the differences in terms of the fuel properties of both types of spent grain were much less stark, in comparison to the differences between the respective beers. The use of HTC as a pretreatment of BSG for subsequent use as a biorefinery feedstock can be considered beneficial. HTC was helpful in uniformization and improvement of the fuel properties. A significant decrease in the oxygen content and O/C ratio and improved grindability was achieved. The Weber method proved to be feasible for HTC productivity assessment for commercial installations, giving satisfactory results for most of the cases, contrary to traditional ash tracer method, which resulted in significant overestimations of the mass yield.
PDF
