The Rover Environmental Monitoring Station (REMS) is one of NASA/MSL's instruments, which has been designed for measuring ambient pressure, humidity, wind speed and direction, UV radiation, and air ...and ground temperature (GT). The GT-sensor is dedicated to measure the real temperature of the Martian surface, integrating the IR energy coming from the ground. The existing IR spectral data of Martian dust, rocks and sediments allow for comparing the Martian spectra with the spectra of different terrestrial minerals and lithologies, and those of their alteration and weathering products. The FTIR reflectance of a set of selected astrobiologically significant minerals (including oxides, oxi/hydroxides, sulfates, chlorides, opal and clays) and basalt (as the main and most widespread volcanic Martian rock) was measured, considering different mixing amounts, and covering the specific working wavelength range of the REMS' GT-sensor. The results obtained show important percentage increases or decreases of reflectance in the entire wavelength range (e.g. basalt-hematite vs. basalt-magnetite) and specific variations limited to some spectral bands (e.g. basalt-smectite vs. basalt-jasper). The basalt reflectance percentage increases or decreases, even up to 100%, depending on the mixing of the different minerals. This unequivocally confirms the need for considering the chemical-mineralogical assemblages (and their textures) for any investigation and interpretation of Mars surface environment. Some complementary applications of this research on our planet, either in relation to the specific performances and characteristics of the GT-sensor autonomous recalibration system, or those oriented to carrying out similar studies on different types of terrestrial environmental settings, are also described.
Several abdominal-located cancers develop metastasis within the peritoneum, what is called peritoneal carcinomatosis (PC), constituting a clinical challenge in their therapeutical management, often ...leading to poor prognoses. Current multidisciplinary strategies, including cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and pressurized intraperitoneal aerosol chemotherapy (PIPAC), demonstrate efficacy but have limitations. In response, alternative strategies are explored in the drug delivery field for intraperitoneal chemotherapy. Controlled drug delivery offers a promising avenue, maintaining localized drug concentrations for optimal PC management. Drug delivery systems (DDS), including hydrogels, implants, nanoparticles, and hybrid systems, show potential for sustained and region-specific drug release. The present review aims to offer an overview of the advances and current designs of DDS for PC chemotherapy administration, focusing on their composition, main characteristics, and principal experimental outcomes, highlighting the importance of biomaterial rationale design and in vitro/vivo models for their testing. Moreover, since clinical data for human subjects are scarce, we offer a critical discussion of the gap between bench and bedside in DDS translation, emphasizing the need for further research.
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•Emphasis on the chemical and structural properties of drug delivery systems (DDS) for intraperitoneal chemotherapy (IPEC).•Analysis of key findings and clinical potential from testing DDS formulations on in vitro and in vivo cancer models.•Overview of the patent landscape and clinical trials, identifying development constraints to bridge the translational gap.
Abstract
Background
Tn5801 tet(M), a Tn916-like element with site-specific affinity for the 3′ end of the housekeeping gene guaA, may integrate at different chromosomal sites.
Objectives
To ...characterize the genetic context of Tn5801 to define its transfer dynamics and impact on the evolution of Enterococcus faecalis (Efs).
Methods
WGS (Illumina HiSeq 2500) was performed on the Efs clinical strain Ef1 and primary and secondary transconjugants of Efs strains JH2-2 which naturally contains Tn5801.B23, an unusual variant that lacks tet(M), OG1RF and OG1SS carrying different copies of Tn5801-like elements. The transposon structures were analysed using a range of bioinformatics tools allowing us to identify the context of Tn5801-like elements. Growth rates at different tetracycline concentrations (0.5–20 mg/L) were estimated using a Synergy HTX plate reader.
Results
Tn5801.B15 tet(M), 20.3 kb exists and can be transferred either singly or within Tn6648 (53.2 kb), a composite element that comprises Tn5801.B15 and Tn6647, a newly identified 32.8 kb transposon that contains the prgABCT operon of pheromone-responsive plasmids. These transposons are able to integrate at specific 11 nt sequences at the 3′ end of guaA and at other chromosomal sites in Efs genomes, thus being able to generate tandem accretions. These events may increase the number of tet(M) copies, enhancing tetracycline resistance in the recipient strain.
Conclusions
This study describes Tn6647 and Tn6648 (comprising Tn6647 and Tn5801.B15) and highlights the diversity of mechanisms for conjugative mobilization and chromosomal insertion of these elements, which can result in tandem accretion. This strategy would facilitate the adaptation of Efs clones to environmental challenges.
Glutamate grabbers, such as glutamate oxaloacetate transaminase (GOT), have been proposed to prevent excitotoxicity secondary to high glutamate levels in stroke patients. However, the efficacy of ...blood glutamate grabbing by GOT could be dependent on the extent and severity of the disruption of the blood–brain barrier (BBB). Our purpose was to analyze the relationship between GOT and glutamate concentration with the patient’s functional status differentially according to BBB serum markers (soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and leukoaraiosis based on neuroimaging). This retrospective observational study includes 906 ischemic stroke patients. We studied the presence of leukoaraiosis and the serum levels of glutamate, GOT, and sTWEAK in blood samples. Functional outcome was assessed using the modified Rankin Scale (mRS) at 3 months. A significant negative correlation between GOT and glutamate levels at admission was shown in those patients with sTWEAK levels > 2900 pg/mL (Pearson’s correlation coefficient: −0.249; p < 0.0001). This correlation was also observed in patients with and without leukoaraiosis (Pearson’s correlation coefficients: −0.299; p < 0.001 vs. −0.116; p = 0.024). The logistic regression model confirmed the association of higher levels of GOT with lower odds of poor outcome at 3 months when sTWEAK levels were >2900 pg/mL (OR: 0.41; CI 95%: 0.28–0.68; p < 0.0001) or with leukoaraiosis (OR: 0.75; CI 95%: 0.69–0.82; p < 0.0001). GOT levels are associated with glutamate levels and functional outcomes at 3 months, but only in those patients with leukoaraiosis and elevated sTWEAK levels. Consequently, therapies targeting glutamate grabbing might be more effective in patients with BBB dysfunction.
Identifying unequivocal signs of life on Mars is one of the most important objectives for sending missions to the red planet. Here we report Red Stone, a 163-100 My alluvial fan-fan delta that formed ...under arid conditions in the Atacama Desert, rich in hematite and mudstones containing clays such as vermiculite and smectites, and therefore geologically analogous to Mars. We show that Red Stone samples display an important number of microorganisms with an unusual high rate of phylogenetic indeterminacy, what we refer to as "dark microbiome", and a mix of biosignatures from extant and ancient microorganisms that can be barely detected with state-of-the-art laboratory equipment. Our analyses by testbed instruments that are on or will be sent to Mars unveil that although the mineralogy of Red Stone matches that detected by ground-based instruments on the red planet, similarly low levels of organics will be hard, if not impossible to detect in Martian rocks depending on the instrument and technique used. Our results stress the importance in returning samples to Earth for conclusively addressing whether life ever existed on Mars.
Certain local atmospheric anomalies, such as the formation of unusually large ice conglomerations (megacryometeors), have been proposed to be a potential natural hazard for people and aviation, as ...well as geoindicators for fingerprinting larger-scale atmospheric environmental changes. On March 13th 2007, at approximately 10:15 am, an ice chunk weighing about 10 kg fell from the clear-sky and crashed through the roof (around 15 m) of an industrial storage house in Mejorada del Campo, a town located 20 km east from Madrid. The megacryometeor monitoring follow-up and the original investigation presented here includes, for the first time, both logistic and scientific collaboration between the Laboratory of the Environment, Criminalistic Service (SECRIM, the Spanish "Guardia Civil") and academic and scientific institutions (universities and the Spanish National Research Council). We propose that the management procedure of the incident, along with the detailed scientific research and combination of analytical methodologies in different laboratories, can serve as a protocol model for other similar events.
Developmental exposure to toxicants and diet can interact with an individual's genetics and produce long-lasting metabolic adaptations. The different isoforms of the apolipoprotein E (
) are an ...important source of variability in metabolic disorders and influence the response to the pesticide chlorpyrifos (CPF). We aimed to study the epigenetic regulation on feeding control genes and the influence of postnatal CPF exposure,
genotype, and sex, and how these modifications impact on the metabolic response to a high-fat diet (HFD). Both male and female apoE3- and apoE4-TR mice were exposed to CPF on postnatal days 10-15. The DNA methylation pattern of proopiomelanocortin, neuropeptide Y, leptin receptor, and insulin-like growth factor 2 was studied in the hypothalamus. At adulthood, the mice were given a HFD for eight weeks. The results highlight the importance of sex in the epigenetic regulation and the implication of CPF treatment and
genotype. The body weight progression exhibited sex-dimorphic differences, apoE4-TR males being the most susceptible to the effects induced by CPF and HFD. Overall, these results underscore the pivotal role of sex,
genotype, and developmental exposure to CPF on subsequent metabolic disturbances later in life and show that sex is a key variable in epigenetic regulation.
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