Therapeutic Potential of Mesenchymal Stem Cells for Cancer Therapy

Mesenchymal stem cells (MSCs) are among the most frequently used cell type for regenerative medicine. A large number of studies have shown the beneficial effects of MSC-based therapies to treat different pathologies, including neurological disorders, cardiac ischemia, diabetes, and bone and cartilage diseases. However, the therapeutic potential of MSCs in cancer is still controversial. While some studies indicate that MSCs may contribute to cancer pathogenesis, emerging data reported the suppressive effects of MSCs on cancer cells. Because of this reality, a sustained effort to understand when MSCs promote or suppress tumor development is needed before planning a MSC-based therapy for cancer. Herein, we provide an overview on the therapeutic application of MSCs for regenerative medicine and the processes that orchestrates tissue repair, with a special emphasis placed on cancer, including central nervous system tumors. Furthermore, we will discuss the current evidence regarding the double-edged sword of MSCs in oncological treatment and the latest advances in MSC-based anti-cancer agent delivery systems.Junta de Andalucía PI-0272-2017Ministerio de Ciencia, Innovación y Universdad CD16/00118, CP19/00046, PI16/00259, BFU2017-83588-P, CP14/00105, PI18/01590, PI17/02104, PIC18/0010, IC19/0052Juvenile Diabetes Research Foundation (USA) 2-SRA-2019-837-S-BFundación Española para la Ciencia y la Tecnología 2018-00023

No-core shell model for 48-Ca, 48-Sc and 48-Ti

We report the first no-core shell model results for $^{48}Ca$, $^{48}Sc$ and $^{48}Ti$ with derived and modified two-body Hamiltonians. We use an oscillator basis with a limited $\hbar\Omega$ range around $45/A^{1/3}-25/A^{2/3} = 10.5 MeV$ and a limited model space up to $1\hbar\Omega$. No single-particle energies are used. We find that the charge dependence of the bulk binding energy of eight A=48 nuclei is reasonably described with an effective Hamiltonian derived from the CD-Bonn interaction while there is an overall underbinding by about 0.4 MeV/nucleon. However, the resulting spectra exhibit deficiencies that are anticipated due to: (1) basis space limitations and/or the absence of effective many-body interactions; and, (2) the absence of genuine three-nucleon interactions. We then introduce additive isospin-dependent central terms plus a tensor force to our Hamiltonian and achieve accurate binding energies and reasonable spectra for all three nuclei. The resulting no-core shell model opens a path for applications to the double-beta ($\beta\beta$) decay process.Comment: Revised content and added reference

Oral particle uptake and organ targeting drives the activity of amphotericin B nanoparticles

There are very few drug delivery systems that target key organs via the oral route, as oral delivery advances normally address gastrointestinal drug dissolution, permeation, and stability. Here we introduce a nanomedicine in which nanoparticles, while also protecting the drug from gastric degradation, are taken up by the gastrointestinal epithelia and transported to the lung, liver, and spleen, thus selectively enhancing drug bioavailability in these target organs and diminishing kidney exposure (relevant to nephrotoxic drugs). Our work demonstrates, for the first time, that oral particle uptake and translocation to specific organs may be used to achieve a beneficial therapeutic response. We have illustrated this using amphotericin B, a nephrotoxic drug encapsulated within <i>N</i>-palmitoyl-<i>N</i>-methyl-<i>N</i>,<i>N</i>-dimethyl-<i>N</i>,<i>N</i>,<i>N</i>-trimethyl-6-<i>O</i>-glycol chitosan (GCPQ) nanoparticles, and have evidenced our approach in three separate disease states (visceral leishmaniasis, candidiasis, and aspergillosis) using industry standard models of the disease in small animals. The oral bioavailability of AmB-GCPQ nanoparticles is 24%. In all disease models, AmB-GCPQ nanoparticles show comparable efficacy to parenteral liposomal AmB (AmBisome). Our work thus paves the way for others to use nanoparticles to achieve a specific targeted delivery of drug to key organs via the oral route. This is especially important for drugs with a narrow therapeutic index

A photometric study of Be stars located in the seismology fields of COROT

Context. In preparation for the COROT mission, an exhaustive photometric study of Be stars located in the seismology fields of the mission has been performed. The very precise and long-time-spanned photometric observations gathered by the COROT satellite will give important clues on the origin of the Be phenomenon. Aims. The aim of this work is to find short-period variable Be stars located in the seismology fields of COROT, and to study and characterise their pulsational properties. Methods. Light curves obtained at the Observatorio de Sierra Nevada, together with data from Hipparcos and ASAS-3 for a total of 84 Be stars, were analysed in order to search for short-term variations. We applied standard Fourier techniques and non-linear least-square fitting to the time series. Results. We found 7 multiperiodic, 21 mono-periodic and 26 non-variable Be stars. Short-term variability was detected in 74% of early-type Be stars and in 31% of mid- to late-type Be stars. We show that non-radial pulsations are more frequent among Be stars than in slow-rotating B stars of the same spectral [email protected]; [email protected]

No changes in parieto-occipital alpha during neural phase locking to visual quasi-periodic theta-, alpha-, and beta-band stimulation

Recent studies have probed the role of the parieto‐occipital alpha rhythm (8 – 12 Hz) in human visual perception through attempts to drive its neural generators. To that end, paradigms have used high‐intensity strictly‐periodic visual stimulation that created strong predictions about future stimulus occurrences and repeatedly demonstrated perceptual consequences in line with an entrainment of parieto‐occipital alpha. Our study, in turn, examined the case of alpha entrainment by non‐predictive low‐intensity quasi‐periodic visual stimulation within theta‐ (4 – 7 Hz), alpha‐ (8 – 13 Hz) and beta (14 – 20 Hz) frequency bands, i.e. a class of stimuli that resemble the temporal characteristics of naturally occurring visual input more closely. We have previously reported substantial neural phase‐locking in EEG recording during all three stimulation conditions. Here, we studied to what extent this phase‐locking reflected an entrainment of intrinsic alpha rhythms in the same dataset. Specifically, we tested whether quasi‐periodic visual stimulation affected several properties of parieto‐occipital alpha generators. Speaking against an entrainment of intrinsic alpha rhythms by non‐predictive low‐intensity quasi‐periodic visual stimulation, we found none of these properties to show differences between stimulation frequency bands. In particular, alpha band generators did not show increased sensitivity to alpha band stimulation and Bayesian inference corroborated evidence against an influence of stimulation frequency. Our results set boundary conditions for when and how to expect effects of entrainment of alpha generators and suggest that the parieto‐occipital alpha rhythm may be more inert to external influences than previously thought

Frame transformation and geoid undulation transfer to GNSS real time positions through the new RTCM 3.1 transformation messages

Radio Technical Commission for Marine Services (RTCM) standardised messages play an important role in real time Global Navigation Satellite Systems (GNSS) applications such as navigation, positioning, civil engineering, surveying, and cartographic or cadastral production. One of the latest agreements on RTCM definitions contains the data fields for real time geodetic reference frame transformation and orthometric heights computation by received geoid undulations via internet protocol. These parameters can be generated dynamically by a GNSS data centre in a network of reference stations, encapsulated in RTCM messages and broadcasted to the rover location so they are centrally administered and the same frame transformations and geoid model are available to every user in the field, obtaining results in a local reference frame in real time. This paper summarises the functionality of the new RTCM 3?1 transformation messages, describes limitations and provides ideas about the possible use for solving specific problems. Test field campaigns are used to describe the real performance and usefulness of these new RTCM 3?1 messagesCapilla Roma, R.; Martín Furones, ÁE.; Anquela Julián, AB.; Berné Valero, JL. (2012). Frame transformation and geoid undulation transfer to GNSS real time positions through the new RTCM 3.1 transformation messages. Survey Review. 44(324):30-36. doi:10.1179/1752270611Y.0000000010S303644324Benciolini, B., Biagi, L., Crespi, M., Manzino, A. M., & Roggero, M. (2008). Reference frames for GNSS positioning services: Some problems and proposed solutions. Journal of Applied Geodesy, 2(1). doi:10.1515/jag.2008.006González-Matesanz, J., Dalda, A., & Malpica, J. A. (2006). A RANGE OF ED50-ETRS89 DATUM TRANSFORMATION MODELS TESTED ON THE SPANISH GEODETIC NETWORK. Survey Review, 38(302), 654-667. doi:10.1179/sre.2006.38.302.654Soler, T., & Marshall, J. (2003). A note on frame transformations with applications to geodetic datums. GPS Solutions, 7(2), 148-149. doi:10.1007/s10291-003-0063-

Characterisation and expression of calpain family members in relation to nutritional status, diet composition and flesh texture in gilthead sea bream (Sparus aurata).

Calpains are non-lysosomal calcium-activated neutral proteases involved in a wide range of cellular processes including muscle proteolysis linked to post-mortem flesh softening. The aims of this study were (a) to characterise several members of the calpain system in gilthead sea bream and (b) to examine their expression in relation to nutritional status and muscle tenderisation. We identified the complete open reading frame of gilthead sea bream calpains1-3, sacapn1, sacapn2, sacapn3, and two paralogs of the calpain small subunit1, sacapns1a and sacapns1b. Proteins showed 63-90% sequence identity compared with sequences from mammals and other teleost fishes, and the characteristic domain structure of vertebrate calpains. Transcripts of sacapn1, sacapn2, sacapns1a and sacapns1b had a wide tissue distribution, whereas sacapn3 was almost exclusively detected in skeletal muscle. Next, we assessed transcript expression in skeletal muscle following alteration of nutritional status by (a) fasting and re-feeding or (b) feeding four experimental diets with different carbohydrate-to-protein ratios. Fasting significantly reduced plasma glucose and increased free fatty acids and triglycerides, together with a significant increase in sacapns1b expression. Following 7 days of re-feeding, plasma parameters returned to fed values and sacapn1, sacapn2, sacapns1a and sacapns1b expression was significantly reduced. Furthermore, an increase in dietary carbohydrate content (11 to 39%) diminished growth but increased muscle texture, which showed a significant correlation with decreased sacapn1 and sacapns1a expression, whilst the other calpains remained unaffected. This study has demonstrated that calpain expression is modulated by nutritional status and diet composition in gilthead sea bream, and that the expression of several calpain members is correlated with muscle texture, indicating their potential use as molecular markers for flesh quality in aquaculture production

Denial of long-term issues with agriculture on tropical peatlands will have devastating consequences

Letter to the Editor

The synaptonemal complex imposes crossover interference and heterochiasmy in Arabidopsis

International audienceMeiotic crossovers (COs) have intriguing patterning properties, including CO interference, the tendency of COs to be well-spaced along chromosomes, and heterochiasmy, the marked difference in male and female CO rates. During meiosis, transverse filaments transiently associate the axes of homologous chromosomes, a process called synapsis that is essential for CO formation in many eukaryotes. Here, we describe the spatial organization of the transverse filaments in Arabidopsis (ZYP1) and show it to be evolutionary conserved. We show that in the absence of ZYP1 ( zyp1a zyp1b null mutants), chromosomes associate in pairs but do not synapse. Unexpectedly, in absence of ZYP1, CO formation is not prevented but increased. Furthermore, genome-wide analysis of recombination revealed that CO interference is abolished, with the frequent observation of close COs. In addition, heterochiasmy was erased, with identical CO rates in males and females. This shows that the tripartite synaptonemal complex is dispensable for CO formation and has a key role in regulating their number and distribution, imposing CO interference and heterochiasmy

Does BERT Understand Code? : An Exploratory Study on the Detection of Architectural Tactics in Code

Quality-driven design decisions are often addressed by using architectural tactics that are re-usable solution options for certain quality concerns. Creating traceability links for these tactics is useful but costly. Automating the creation of these links can help reduce costs but is challenging as simple structural analyses only yield limited results. Transfer-learning approaches using language models like BERT are a recent trend in the field of natural language processing. These approaches yield state-of-the-art results for tasks like text classification. In this paper, we experiment with treating detection of architectural tactics in code as a text classification problem. We present an approach to detect architectural tactics in code by fine-tuning BERT. A 10-fold cross-validation shows promising results with an average F1-Score of 90%, which is on a par with state-of-the-art approaches. We additionally apply our approach on a case study, where the results of our approach show promising potential but fall behind the state-of-the-art. Therefore, we discuss our approach and look at potential reasons as well as downsides and future work