Miracle-dz/UniFAR-FTUs huggingface dataset:
Validation of a UHPLC-MS/MS Method to Quantify Twelve Antiretroviral Drugs within Peripheral Blood Mononuclear Cells from People Living with HIV

Recently, anti-HIV treatment has achieved high efficacy and tolerability. Nevertheless, few data are available about the intracellular penetration of antiretrovirals, partly due to the technical challenges related to intracellular quantification. This work aimed to validate an ultra-high performance liquid chromatography (UHPLC) tandem mass spectrometry (MS/MS) method for the simultaneous quantification of maraviroc, nevirapine, rilpivirine, dolutegravir, raltegravir, cobicistat, darunavir, ritonavir, atazanavir, efavirenz, elvitegravir, and etravirine within peripheral blood mononuclear cells (PBMCs) and apply it to samples from patients. PBMCs were isolated by density gradient on cell preparation tubes (CPT). Samples were prepared by addition of internal standards (IS), sonication, centrifugation, and drying. Reconstituted extracts underwent chromatographic separation by reversed phase UHPLC and detection was performed by electrospray ionization and multiple reaction monitoring. Method validation followed FDA and EMA guidelines, showing acceptable accuracy, precision, recovery and IS-normalized matrix effect. The application to 56 samples from patients undergoing antiretroviral treatment provided description of intracellular penetration, showing method eligibility for future studies.
Developmental differences in children’s and adults’ use of geometric information in map-reading tasks

Using maps effectively requires the ability to scale distances while preserving angle and orientation, the three properties of Euclidean geometry. The aim of the current study was twofold: first, to examine how the ability to represent and use these Euclidean properties changes with development when scaling maps in object-to-object relationships and, second, to explore the effects on the scaling performance of two variables of the array of objects, type of angular configuration and relative vector length. To this end, we tested seventy-five 4-, 6-, and 8-year-old children, as well as twenty-five adults, in a simple completion task with different linear and triangular configurations of objects. This study revealed important developmental changes between 4 and 6 years of age and between 8 years of age and adulthood for both distance and angle representation, while it also showed that the configuration variables affected younger and older children’s performances in different ways when scaling distances and preserving angles and orientation. This study was instrumental in showing that, from an early age, children are able to exploit an intrinsic system of reference to scale geometrical configurations of objects.
Stability of Patches of Higher Population Density within the Heterogenous Distribution of the Gray Field Slug Deroceras reticulatum in Arable Fields in the UK

Simple Summary There is growing public and legislative pressure to reduce the use of pesticides in crop production. It is thought that the gray field slug is not uniformly distributed in arable fields, but that patches of higher slug densities occur, interspersed within areas of lower slug numbers. Targeting molluscicide applications only at these patches, leaving other areas untreated, would substantially reduce the amount of molluscicide used but relies on patches being a feature of slug populations in all susceptible crops, and always occurring in the same places during the periods slug control is needed. This study investigated these requirements in 22 commercial arable field crops from different regions of the UK, and in three different years. Despite a variable proportion of slug populations being found below the soil surface (where they could not be assessed) on different sampling dates, existence of higher density patches were confirmed in all fields, although it was noted that, when too few slugs were active on the soil surface, they could not be reliably detected. When they were detected, they occurred in the same locations in each field. The potential for using these patches in more sustainable slug control approaches is discussed. Abstract Exploitation of heterogenous distributions of Deroceras reticulatum, in arable fields by targeting molluscicide applications toward areas with higher slug densities, relies on these patches displaying sufficient spatio-temporal stability. Regular sampling of slug activity/distribution was undertaken using 1 ha rectangular grids of 100 refuge traps established in 22 commercial arable field crops. Activity varied significantly between the three years of the study, and the degree of aggregation (Taylor’s Power Law) was higher in fields with higher mean trap catches. Hot spot analysis detected statistically significant spatial clusters in all fields, and in 162 of the 167 individual assessment visits. The five assessment visits in which no clusters were detected coincided with low slug activity (≤0.07 per trap). Generalized Linear Models showed significant spatial stability of patches in 11 fields, with non-significant fields also characterized by low slug activity (≤1.2 per trap). Mantel’s permutation tests revealed a high degree of correlation between location of individual patches between sampling dates. It was concluded that patches of higher slug density were spatio-temporally stable, but detection using surface refuge traps (which rely on slug activity on the soil surface) was less reliable when adverse environmental conditions resulted in slugs retreating into the upper soil horizons.
Characterization of Laser-Induced Breakdown Spectroscopy (LIBS) for Application to Space Exploration

Early in the next century, several space missions are planned with the goal of landing craft on asteroids, comets, the Moon, and Mars. To increase the scientific return of these missions, new methods are needed to provide (1) significantly more analyses per mission lifetime, and (2) expanded analytical capabilities. One method that has the potential to meet both of these needs for the elemental analysis of geological samples is laser-induced breakdown spectroscopy (LIBS). These capabilities are possible because the laser plasma provides rapid analysis and the laser pulse can be focused on a remotely located sample to perform a stand-off measurement. Stand-off is defined as a distance up to 20 m between the target and laser. Here we present the results of a characterization of LIBS for the stand-off analysis of soils at reduced air pressures and in a simulated Martian atmosphere (5–7 torr pressure of CO2) showing the feasibility of LIBS for space exploration. For example, it is demonstrated that an analytically useful laser plasma can be generated at distances up to 19 m by using only 35 mJ/pulse from a compact laser. Some characteristics of the laser plasma at reduced pressure were also investigated. Temporally and spectrally resolved imaging showed significant changes in the plasma as the pressure was reduced and also showed that the analyte signals and mass ablated from a target were strongly dependent on pressure. As the pressure decreased from 590 torr to the 40–100 torr range, the signals increased by a factor of about 3–4, and as the pressure was further reduced the signals decreased. This behavior can be explained by pressure-dependent changes in the mass of material vaporized and the frequency of collisions between species in the plasma. Changes in the temperature and the electron density of the plasmas with pressure were also examined and detection limits for selected elements were determined.
PI3K/AKT/mTOR Signaling Pathway in Breast Cancer: From Molecular Landscape to Clinical Aspects

Breast cancer is a serious health problem worldwide, representing the second cause of death through malignancies among women in developed countries. Population, endogenous and exogenous hormones, and physiological, genetic and breast-related factors are involved in breast cancer pathogenesis. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) is a signaling pathway involved in cell proliferation, survival, invasion, migration, apoptosis, glucose metabolism and DNA repair. In breast tumors, PIK3CA somatic mutations have been reported, located in exon 9 and exon 20. Up to 40% of PIK3CA mutations are estrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) -negative in primary and metastatic breast cancer. HER2 is overexpressed in 20–30% of breast cancers. HER1, HER2, HER3 and HER4 are membrane receptor tyrosine kinases involved in HER signaling to which various ligands can be attached, leading to PI3K/AKT activation. Currently, clinical studies evaluate inhibitors of the PI3K/AKT/mTOR axis. The main purpose of this review is to present general aspects of breast cancer, the components of the AKT signaling pathway, the factors that activate this protein kinase B, PI3K/AKT-breast cancer mutations, PI3K/AKT/mTOR-inhibitors, and the relationship between everolimus, temsirolimus and endocrine therapy.
Comparative Proteomics of Marinobacter sp. TT1 Reveals Corexit Impacts on Hydrocarbon Metabolism, Chemotactic Motility, and Biofilm Formation

The application of chemical dispersants during marine oil spills can affect the community composition and activity of marine microorganisms. Several studies have indicated that certain marine hydrocarbon-degrading bacteria, such as Marinobacter spp. , can be inhibited by chemical dispersants, resulting in lower abundances and/or reduced biodegradation rates. However, a major knowledge gap exists regarding the mechanisms underlying these physiological effects. Here, we performed comparative proteomics of the Deepwater Horizon isolate Marinobacter sp. TT1 grown under different conditions. Strain TT1 received different carbon sources (pyruvate vs. n-hexadecane) with and without added dispersant (Corexit EC9500A). Additional treatments contained crude oil in the form of a water-accommodated fraction (WAF) or chemically-enhanced WAF (CEWAF; with Corexit). For the first time, we identified the proteins associated with alkane metabolism and alginate biosynthesis in strain TT1, report on its potential for aromatic hydrocarbon biodegradation and present a protein-based proposed metabolism of Corexit components as carbon substrates. Our findings revealed that Corexit exposure affects hydrocarbon metabolism, chemotactic motility, biofilm formation, and induces solvent tolerance mechanisms, like efflux pumps, in strain TT1. This study provides novel insights into dispersant impacts on microbial hydrocarbon degraders that should be taken into consideration for future oil spill response actions.
Effective Elimination and Biodegradation of Polycyclic Aromatic Hydrocarbons from Seawater through the Formation of Magnetic Microfibres

Supramolecular aggregates formed between polycyclic aromatic hydrocarbons and either naphthalene or perylene-derived diimides have been anchored in magnetite magnetic nanoparticles. The high affinity and stability of these aggregates allow them to capture and confine these extremely carcinogenic contaminants in a reduced space. In some cases, the high cohesion of these aggregates leads to the formation of magnetic microfibres of several microns in length, which can be isolated from the solution by the direct action of a magnet. Here we show a practical application of bioremediation aimed at the environmental decontamination of naphthalene, a very profuse contaminant, based on the uptake, sequestration, and acceleration of the biodegradation of the formed supramolecular aggregate, by the direct action of a bacterium of the lineage Roseobacter (biocompatible with nanostructured receptors and very widespread in marine environments) without providing more toxicity to the environment.
The Homestead: Developing a Conceptual Framework through Co-Creation for Innovating Long-Term Dementia Care Environments

Alternative care environments for regular nursing homes are highly warranted to promote health and well-being of residents with dementia that are part of an age-friendly and dementia-friendly city and society. Insight is lacking on how to translate evidence-based knowledge from theory into a congruent conceptual model for innovation in current practice. This study reports on the co-creation of an alternative nursing home model in the Netherlands. A participatory research approach was used to co-create a conceptual framework with researchers, practitioners and older people following an iterative process. Results indicate that achieving positive outcomes for people with dementia, (in)formal caregivers, and the community is dependent on how well the physical, social and organizational environment are congruently designed. The theoretical underpinnings of the conceptual model have been translated into “the homestead,” which is conceptualized around three main pillars: activation, freedom and relationships. The Homestead Care Model is an illustrative example of how residential care facilities can support the development of age-friendly communities that take into consideration the needs and requirements of older citizens. However, challenges remain to implement radical changes within residential care. More research is needed into the actual implementation of the Homestead Care Model.
A Comparison of Various Surgical Treatments for Degenerative Cervical Myelopathy: A Propensity Score Matched Analysis

Study Design: Retrospective Cohort. Objective: To compare the short-term outcomes for Laminoplasty, Laminectomy/fusion, and ACDF. Methods: We utilized a prospectively-collected, multi-center national database with a propensity score matching algorithm to compare the short-term outcomes for laminoplasty, laminectomy/fusion, and multi-level (>3) ACDF (with and without corpectomy). Bivariate analyses involved both chi-square/fisher exact test and t-test/ANOVA on perioperative factors. Multivariate analyses were performed to determined independent risk factors for short term outcomes. Results: 546 patients remained after propensity score matching, with 182 patients in each cohort. ACDF required the longest operative time 188 ± 79 versus laminectomy/fusion (169 ± 75, p = 0.017), and laminoplasty (167 ± 66, p = 0.004). ACDF required the shortest hospital stay (LOS ≥ 2: ACDF 56.6%, laminoplasty 89.6%, laminectomy/fusion 93.4%, p < 0.05). ACDF had lower overall complications (ACDF 3.9%, laminoplasty 7.7%, laminectomy/fusion 11.5%, p < 0.05), mortality (ACDF 0%, laminoplasty 0.55%, laminectomy/fusion 2.2%, p < 0.05), and unplanned readmissions (ACDF 4.4%, laminoplasty 4.4%, laminectomy/fusion 9.9%, p < 0.05). No significant differences were seen in the other outcomes including DVT/PT, acute renal failure, UTI, stroke, cardiac complications, or sepsis. In the multivariate analysis, laminectomy/fusion (OR 17, reference: ACDF) and laminoplasty (OR10, reference: ACDF) were strong independent risk factors for LOS ≥ 2 days. Laminectomy/fusion (OR 3.2, reference: ACDF) was an independent predictor for any adverse events 30-days after surgery. Conclusions: Laminectomy/fusion carries the highest risk for morbidity, mortality, and unplanned readmissions in the short-term postoperative period. Laminoplasty and ACDF cases carry similar short-term complications risks. ACDF is significantly associated with the longest operative duration and shortest LOS without an increase in individual or overall complications, readmissions, or reoperations
Diversity and Colonization Strategies of Endolithic Cyanobacteria in the Cold Mountain Desert of Pamir

Microorganisms can survive in extreme environments and oligotrophic habitats thanks to their specific adaptive capacity. Due to its severe and contrasting climate conditions, the cold mountain desert in Eastern Pamir provides a unique environment for analyzing microbial adaptation mechanisms occurring within colonization of endolithic habitats. This study aims to investigate the composition and structure of endolithic microbial communities and analyze the interactions between microorganisms and colonized lithic substrates. Endolithic biofilms were examined using scanning electron microscopy in backscattered electron mode (SEM-BSE) and next-generation sequencing (NGS) applying amplicon sequence variants (ASVs) approach. The investigation of the V3–V4 region of 16S rRNA gene revealed that endolithic communities are dominated by Actinobacteria (26%), Proteobacteria (23%), and Cyanobacteria (11.4%). Cyanobacteria were represented by Oxyphotobacteria with a predominance of subclasses of Oscillatoriophycidae, Synechococcophycideae, and Nostocophycidae as well as the rarely occurring Sericytochromatia. The positive correlation between the contribution of the orders Synechococcales and Rhizobiales to community structure suggests that some functionally closed taxa of Cyanobacteria and Proteobacteria can complement each other, for example, in nitrogen fixation in endolithic communities. The endolithic communities occurring in Eastern Pamir were identified as complex systems whose composition and structure seem to be influenced by the architecture of microhabitats and related microenvironmental conditions.
Effect of Amyloid-β Monomers on Lipid Membrane Mechanical Parameters–Potential Implications for Mechanically Driven Neurodegeneration in Alzheimer’s Disease

Alzheimer’s disease (AD) is a neurodegenerative disease that results in memory loss and the impairment of cognitive skills. Several mechanisms of AD’s pathogenesis were proposed, such as the progressive accumulation of amyloid-β (Aβ) and τ pathology. Nevertheless, the exact neurodegenerative mechanism of the Aβ remains complex and not fully understood. This paper proposes an alternative hypothesis of the mechanism based on maintaining the neuron membrane’s mechanical balance. The incorporation of Aβ decreases the lipid membrane’s elastic properties, which eventually leads to the impairment of membrane clustering, disruption of mechanical wave propagation, and change in gamma oscillations. The first two disrupt the neuron’s ability to function correctly while the last one decreases sensory encoding and perception enabling. To begin discussing this mechanical-balance hypothesis, we measured the effect of two selected peptides, Aβ-40 and Aβ-42, as well as their fluorescently labeled modification, on membrane mechanical properties. The decrease of bending rigidity, consistent for all investigated peptides, was observed using molecular dynamic studies and experimental flicker-noise techniques. Additionally, wave propagation was investigated with molecular dynamic studies in membranes with and without incorporated neurodegenerative peptides. A change in membrane behavior was observed in the membrane system with incorporated Aβ.
Distribution of boron and its forms in young “Newhall” navel orange (Citrus sinensis Osb.) plants grafted on two rootstocks in response to deficient and excessive boron

Boron (B) deficiency is widespread and serious in navel orange orchards in southern Jiangxi in China and has been considered an important soil constraint to citrus yield and quality. It has been observed that there was great variation in responses to different B supply levels between “Newhall” navel orange grafted on citrange and trifoliate orange. The aim of this work was to compare the different responses of the two scion-rootstock combinations under different B stresses (low and high) in young citrus trees. “Newhall” navel orange grafted on citrange or trifoliate orange were incubated in nutrient solution containing different levels of B (0, 0.5 and 5.0 mg L−1), of which 0 and 5.0 mg L−1 were considered as deficient and excessive B and 0.5 mg L−1 was considered as an appropriate level of B. The experiment was carried out in a greenhouse for 117 days. The results showed that, under low B or high B conditions, better growth performance was observed in “Newhall” plants grafted on citrange than in those grafted on trifoliate orange, suggesting that citrange-grafted plants were more tolerant to deficient and excessive B than the plants grafted on trifoliate orange. Boron seemed to be preferentially translocated to the new leaves (leaves from current year), and resulted in normal growth of young leaves under limited B supply. Boron distribution in different plant parts indicated that there was a restriction in translocation of B from roots to scion tissues (stems and leaves of scion) under limited B availability. The relatively high B concentration observed in plants grafted on trifoliate orange suggested higher demand for B than those grafted on citrange. There existed a balance within the B forms to maintain normal growth. Thus, R value (R = semi-bound B/free B) was much higher in citrange-grafted plants than in trifoliate orange-grafted plants under the same B supply level. This explained why citrange-grafted plants had less B but produced relatively more dry mass at cellular level. These results suggested that the utilization efficiency of B of citrange-grafted plants was probably greater than trifoliate orange-grafted plants.
Metal Removal from Contaminated Soil and Sediments by the Biosurfactant Surfactin

Batch soil washing experiments were performed to evaluate the feasibility of using surfactin from Bacillus subtilis, a lipopeptide biosurfactant, for the removal of heavy metals from a contaminated soil and sediments. The soil contained high levels of metals and hydrocarbons (890 mg/kg of zinc, 420 mg/kg of copper, and 12.6% oil and grease), and the sediments contained 110 mg/kg of copper and 3300 mg/kg of zinc. The contaminated soil was spiked to increase the levels of copper, zinc, and cadmium to 550, 1200, and 2000 mg/kg, respectively. Water alone removed minimal amounts of copper and zinc (less than 1%). Results showed that 0.25% surfactin/1% NaOH could remove 25% of the copper and 6% of the zinc from the soil and 15% of the copper and 6% of the zinc from the sediments. A series of five washings of the soil with 0.25% surfactin (1% NaOH) was able to remove 70% of the copper and 22% of the zinc. The technique of ultrafiltration and the measurement of octanol−water partitioning and ζ-potential were used.
Tissue-selective alternate promoters guide NLRP6 expression

The NLRP6 innate immune sensor is regulated by tissue-selective alternate promoters that facilitate translational gene silencing outside of the intestinal epithelium in both humans and mice. The pryin domain (PYD) domain is involved in protein interactions that lead to assembly of immune-sensing complexes such as inflammasomes. The repertoire of PYD-containing genes expressed by a cell type arms tissues with responses against a range of stimuli. The transcriptional regulation of the PYD gene family however is incompletely understood. Alternative promoter utilization was identified as a mechanism regulating the tissue distribution of human PYD gene family members, including NLRP6 that is translationally silenced outside of intestinal tissue. Results show that alternative transcriptional promoters mediate NLRP6 silencing in mice and humans, despite no upstream genomic synteny. Human NLRP6 contains an internal alternative promoter within exon 2 of the PYD, resulting in a truncated mRNA in nonintestinal tissue. In mice, a proximal promoter was used that expanded the 5′ leader sequence restricting nuclear export and abolishing translational efficiency. Nlrp6 was dispensable in disease models targeting the kidney, which expresses noncanonical isoforms. Thus, alternative promoter use is a critical mechanism not just for isoform modulation but for determining expression profile and function of PYD family members.