There is an important relationship between probiotics, psychobiotics and cognitive and behavioral processes, which include neurological, metabolic, hormonal and immunological signaling pathways; the ...alteration in these systems may cause alterations in behavior (mood) and cognitive level (learning and memory). Psychobiotics have been considered key elements in affective disorders and the immune system, in addition to their effect encompassing the regulation of neuroimmune regulation and control axes (the hypothalamic-pituitary-adrenal axis or HPA, the sympathetic-adrenal-medullary axis or SAM and the inflammatory reflex) in diseases of the nervous system. The aim of this review is to summarize the recent findings about psychobiotics, the brain-gut axis and the immune system. The review focuses on a very new and interesting field that relates the microbiota of the intestine with diseases of the nervous system and its possible treatment, in neuroimmunomodulation area. Indeed, although probiotic bacteria will be concentrated after ingestion, mainly in the intestinal epithelium (where they provide the host with essential nutrients and modulation of the immune system), they may also produce neuroactive substances which act on the brain-gut axis.
Genomic signal processing (GSP) refers to the use of signal processing for the analysis of genomic data. GSP methods require the transformation or mapping of the genomic data to a numeric ...representation. To date, several DNA numeric representations (DNR) have been proposed; however, it is not clear what the properties of each DNR are and how the selection of one will affect the results when using a signal processing technique to analyze them. In this paper, we present an experimental study of the characteristics of nine of the most frequently-used DNR. The objective of this paper is to evaluate the behavior of each representation when used to measure the similarity of a given pair of DNA sequences.
Display omitted
•Poly(butylene succinate-ran-ε-caprolactone) copolyesters were obtained by enzymatic ROP.•Cyclic butylene succinate oligomers and ε-caprolactone were used as feed monomers.•These ...random copolymers are semi-crystalline over the entire range of compositions.•Crystallization studies by DSC, PLOM and WAXS showed that these copolymers are isodimorphic.•They display a pseudo-eutectic region with double crystalline phases.
In this paper, the preparation of PBS-ran-PCL copolyesters by enzymatic ring opening polymerization is presented for the first time. The copolyesters were produced in a wide composition range and free of metallic contaminants, so they may be regarded as potential biomaterials. The copolymers have been characterized by proton and carbon nuclear magnetic resonance (1H and 13C NMR), gel permeation chromatography (GPC), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), polarized light optical microscopy (PLOM) and wide angle X-ray scattering (WAXS). The PBS-ran-PCL copolyesters were able to crystallize in the entire composition range and displayed a pseudo-eutectic region. Most copolymers away from the pseudo-eutectic region exhibited a single crystalline phase (PBS-rich or PCL-rich crystalline phase), while within the pseudo-eutectic region the copolymers were double crystalline. Observations by PLOM, during isothermal crystallization showed that both nucleation density and spherulitic growth rate of the copolyesters are determined by the component that constitutes the majority phase. WAXS studies revealed that d spacings of selected crystallographic planes depend on composition. Therefore, both DSC and WAXS results suggest that the copolymers are probably isodimorphic, as the PBS-rich crystalline phase may contain small inclusions of PCL co-units, while the PCL-rich crystalline domains may also contain a minor quantity of PBS co-units inside.
Bacteria control the expression of specific genes by Quorum Sensing (QS). This works using small signaling molecules called Autoinducers (AIs), for example, the Autoinducer-2 (AI-2). In this work, we ...present a mathematical model that represents the AI-2 dynamics on
, which is linked to the cell growth and the
operon expression. The model is adjusted using experimental data. Our results suggest that the extracellular AI-2 activity level depends on the cell growth rate, and this activity depends on the cell exponential growth phase. The model was adapted to simulate the interference of QS mechanisms in a co-culture of two
strains: a wild type strain and a knock out strain that detects AI-2 but does not produce it. Co-culture simulations unveiled two conditions to avoid the QS on the wild strain: when the knock out takes control of the growth medium and overcomes the wild strain, or when is pre-cultured to its mid-exponential phase and then added to the wild strain culture. Model simulations unveiled new insights about the interference of bacterial communication and offer new tools for QS control.
Xentuzumab-a humanised IgG1 monoclonal antibody-binds IGF-1 and IGF-2, inhibiting their growth-promoting signalling and suppressing AKT activation by everolimus. This phase Ib/II exploratory trial ...evaluated xentuzumab plus everolimus and exemestane in hormone receptor-positive, locally advanced and/or metastatic breast cancer (LA/MBC).
Patients with hormone receptor-positive/HER2-negative LA/MBC resistant to non-steroidal aromatase inhibitors were enrolled. Maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of xentuzumab/everolimus/exemestane were determined in phase I (single-arm, dose-escalation). In phase II (open-label), patients were randomised 1:1 to the RP2D of xentuzumab/everolimus/exemestane or everolimus/exemestane alone. Randomisation was stratified by the presence of visceral metastases. Primary endpoint was progression-free survival (PFS).
MTD was determined as xentuzumab 1000 mg weekly plus everolimus 10 mg/day and exemestane 25 mg/day. A total of 140 patients were enrolled in phase II (70 to each arm). Further recruitment was stopped following an unfavourable benefit-risk assessment by the internal Data Monitoring Committee appointed by the sponsor. Xentuzumab was discontinued; patients could receive everolimus/exemestane if clinically indicated. Median PFS was 7.3 months (95% CI 3.3-not calculable) in the xentuzumab/everolimus/exemestane group and 5.6 months (3.7-9.1) in the everolimus/exemestane group (hazard ratio 0.97, 95% CI 0.57-1.65; P = 0.9057). In a pre-specified subgroup of patients without visceral metastases at screening, xentuzumab/everolimus/exemestane showed evidence of PFS benefit versus everolimus/exemestane (hazard ratio 0.21 0.05-0.98; P = 0.0293). Most common any-cause adverse events in phase II were diarrhoea (29 41.4% in the xentuzumab/everolimus/exemestane group versus 20 29.0% in the everolimus/exemestane group), mucosal inflammation (27 38.6% versus 21 30.4%), stomatitis (24 34.3% versus 24 34.8%), and asthenia (21 30.0% versus 24 34.8%).
Addition of xentuzumab to everolimus/exemestane did not improve PFS in the overall population, leading to early discontinuation of the trial. Evidence of PFS benefit was observed in patients without visceral metastases when treated with xentuzumab/everolimus/exemestane, leading to initiation of the phase II XENERA™-1 trial (NCT03659136).
ClinicalTrials.gov, NCT02123823 . Prospectively registered, 8 March 2013.
This article investigates the influence of a pro-oxidant additive on the accelerated and environmental degradation of linear low density polyethylene (LLDPE) and low density polyethylene (LDPE). ...Extruded cast films (100 μm) were prepared with various amounts of a pro-oxidant (a so-called “Oxo” additive) (0%, 1% and 2% w/w). The films were subjected to either environmental weathering or air oven aging (60 °C) tests for 260 days. The chemical and physical changes induced by aging were monitored by: Gel Permeation Chromatography (GPC), Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Successive Self-nucleation and Annealing (SSA) thermal fractionation and tensile tests. Neat PE samples did not exhibit significant changes during the period evaluated. Crystallinity obtained from standard DSC tests during accelerated degradation exhibited variations due to a combination between annealing and recrystallization after chain scission. For both accelerated and environmental degradation a complete loss of mechanical properties was obtained although at different exposure times. SSA was shown to be the most sensitive technique applied since it evidenced early structural changes during degradation in LLDPE and LDPE that were undetected by GPC, tensile tests (i.e., strain at break) or FTIR at identical exposure times. SSA tests after accelerated degradation revealed that LLDPE linear sequences in between branching points are substantially more affected at longer exposure times than those in LDPE, a result that may imply differences in degradation mechanisms during the later stages of the degradation process.
We aimed to assess the potential of baculoviral vectors (BV) for brain cancer gene therapy. We compared them with adenoviral vectors (AdV), which are used in neuro-oncology, but for which there is ...pre-existing immunity. We constructed BVs and AdVs encoding fluorescent reporter proteins and evaluated their transduction efficiency in glioma cells and astrocytes. Naïve and glioma-bearing mice were intracranially injected with BVs to assess transduction and neuropathology. Transgene expression was also assessed in the brain of BV-preimmunized mice. While the expression of BVs was weaker than AdVs in murine and human glioma cell lines, BV-mediated transgene expression in patient-derived glioma cells was similar to AdV-mediated transduction and showed strong correlation with clathrin expression, a protein that interacts with the baculovirus glycoprotein GP64, mediating BV endocytosis. BVs efficiently transduced normal and neoplastic astrocytes in vivo, without apparent neurotoxicity. BV-mediated transgene expression was stable for at least 21 days in the brain of naïve mice, but it was significantly reduced after 7 days in mice systemically preimmunized with BVs. Our findings indicate that BVs efficiently transduce glioma cells and astrocytes without apparent neurotoxicity. Since humans do not present pre-existing immunity against BVs, these vectors may constitute a valuable tool for the delivery of therapeutic genes into the brain.
The search for the minimum information required for an organism to sustain a cellular system network has rendered both the identification of a fixed number of known genes and those genes whose ...function remains to be identified. The approaches used in such search generally focus their analysis on coding genomic regions, based on the genome to proteic-product perspective. Such approaches leave other fundamental processes aside, mainly those that include higher-level information management. To cope with this limitation, a non-genocentric approach based on genomic sequence analysis using language processing tools and gene ontology may prove an effective strategy for the identification of those fundamental genomic elements for life autonomy. Additionally, this approach will provide us with an integrative analysis of the information value present in all genomic elements, regardless of their coding status.
Colorectal cancer (CRC) represents the third most common malignancy and the second leading cause of cancer-related deaths worldwide. Although immunotherapy has taken center stage in mainstream ...oncology, it has shown limited clinical efficacy in CRC, generating an urgent need for discovery of new biomarkers and potential therapeutic targets. Galectin-1 (Gal-1), an endogenous glycan-binding protein, induces tolerogenic programs and contributes to tumor cell evasion of immune responses. Here, we investigated the relevance of Gal-1 in CRC and explored its modulatory activity within the CD8
regulatory T cell (Treg) compartment. Mice lacking Gal-1 (
) developed a lower number of tumors and showed a decreased frequency of a particular population of CD8
CD122
PD-1
Tregs in the azoxymethane-dextran sodium sulfate model of colitis-associated CRC. Moreover, silencing of tumor-derived Gal-1 in the syngeneic CT26 CRC model resulted in reduced number and attenuated immunosuppressive capacity of CD8
CD122
PD-1
Tregs, leading to slower tumor growth. Moreover, stromal Gal-1 also influenced the fitness of CD8
Tregs, highlighting the contribution of both tumor and stromal-derived Gal-1 to this immunoregulatory effect. Finally, bioinformatic analysis of a colorectal adenocarcinoma from The Cancer Genome Atlas dataset revealed a particular signature characterized by high CD8
Treg score and elevated Gal-1 expression, which delineates poor prognosis in human CRC. Our findings identify CD8
CD122
PD-1
Tregs as a target of the immunoregulatory activity of Gal-1, suggesting a potential immunotherapeutic strategy for the treatment of CRC.
Genomic signal processing (GSP) refers to the use of digital signal processing (DSP) tools for analyzing genomic data such as DNA sequences. A possible application of GSP that has not been fully ...explored is the computation of the distance between a pair of sequences. In this work we present GAFD, a novel GSP alignment-free distance computation method. We introduce a DNA sequence-to-signal mapping function based on the employment of doublet values, which increases the number of possible amplitude values for the generated signal. Additionally, we explore the use of three DSP distance metrics as descriptors for categorizing DNA signal fragments. Our results indicate the feasibility of employing GAFD for computing sequence distances and the use of descriptors for characterizing DNA fragments.
PDF
