Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of transporters in regulating mammalian intracellular inorganic phosphate

This review summarizes the current understanding of the role of plasma membrane transporters in regulating intracellular inorganic phosphate ([Pi]In) in mammals. Pi influx is mediated by SLC34 and SLC20 Na+-Pi cotransporters. In non-epithelial cells other than erythrocytes, Pi influx via SLC20 transporters PiT1 and/or PiT2 is balanced by efflux through XPR1 (xenotropic and polytropic retrovirus receptor 1). Two new pathways for mammalian Pi transport regulation have been described recently: 1) in the presence of adequate Pi, cells continuously internalize and degrade PiT1. Pi starvation causes recycling of PiT1 from early endosomes to the plasma membrane and thereby increases the capacity for Pi influx; and 2) binding of inositol pyrophosphate InsP8 to the SPX domain of XPR1 increases Pi efflux. InsP8 is degraded by a phosphatase that is strongly inhibited by Pi. Therefore, an increase in [Pi]In decreases InsP8 degradation, increases InsP8 binding to SPX, and increases Pi efflux, completing a feedback loop for [Pi]In homeostasis. Published data on [Pi]In by magnetic resonance spectroscopy indicate that the steady state [Pi]In of skeletal muscle, heart, and brain is normally in the range of 1–5 mM, but it is not yet known whether PiT1 recycling or XPR1 activation by InsP8 contributes to Pi homeostasis in these organs. Data on [Pi]In in cultured cells are variable and suggest that some cells can regulate [Pi] better than others, following a change in [Pi]Ex. More measurements of [Pi]In, influx, and efflux are needed to determine how closely, and how rapidly, mammalian [Pi]In is regulated during either hyper- or hypophosphatemia.
A maladaptive pleural environment suppresses preexisting anti-tumor activity of pleural infiltrating T cells

Introduction Treatment options for patients with malignant pleural effusions (MPE) are limited due, at least in part, to the unique environment of the pleural space, which drives an aggressive tumor state and governs the behavior of infiltrating immune cells. Modulation of the pleural environment may be a necessary step toward the development of effective treatments. We examine immune checkpoint molecule (ICM) expression on pleural T cells, the secretomes of pleural fluid, pleural infiltrating T cells (PIT), and ability to activate PIT ex vivo. Methods ICM expression was determined on freshly drained and in vitro activated PIT from breast, lung and renal cell cancer. Secretomics (63 analytes) of activated PIT, primary tumor cultures and MPE fluid was determined using Luminex technology. Complementary digital spatial proteomic profiling (42 analytes) of CD45+ MPE cells was done using the Nanostring GeoMx platform. Cytolytic activity was measured against autologous tumor targets. Results ICM expression was low on freshy isolated PIT; regulatory T cells (T-reg) were not detectable by GeoMx. In vitro activated PIT coexpressed PD-1, LAG-3 and TIGIT but were highly cytotoxic against autologous tumor and uniquely secreted cytokines and chemokines in the > 100 pM range. These included CCL4, CCL3, granzyme B, IL-13, TNFα, IL-2 IFNγ, GM-CSF, and perforin. Activated PIT also secreted high levels of IL-6, IL-8 and sIL-6Rα, which contribute to polarization of the pleural environment toward wound healing and the epithelial to mesenchymal transition. Addition of IL-6Rα antagonist to cultures reversed tumor EMT but did not alter PIT activation, cytokine secretion or cytotoxicity. Discussion Despite the negative environment, immune effector cells are plentiful, persist in MPE in a quiescent state, and are easily activated and expanded in culture. Low expression of ICM on native PIT may explain reported lack of responsiveness to immune checkpoint blockade. The potent cytotoxic activity of activated PIT and a proof-of-concept clinical scale GMP-expansion experiment support their promise as a cellular therapeutic. We expect that a successful approach will require combining cellular therapy with pleural conditioning using immune checkpoint blockers together with inhibitors of upstream master cytokines such as the IL-6/IL-6R axis.
Family listening/circle program: The experience of community action projects to promote family and community wellness in three tribal communities in New Mexico

Introduction The Family Listening/Circle Program (FLCP) is a community-based participatory research (CBPR), culture-centered, intergenerational family strengthening program that was co-developed in partnership with the University of New Mexico's Center for Participatory Research (UNM-CPR) and three tribal communities (Pueblo of Jemez, Ramah Navajo, and Mescalero Apache) in New Mexico. The Family Listening/Circle Program brings together fourth and fifth graders, their parents, caregivers, and elders to reduce risky behaviors associated with the initiation of substance use among the youth, and to strengthen family communication and connectedness to culture and language as protective factors. Methods The tribal research teams (TRTs) from each community worked with UNM-CPR to co-create, pilot, implement, and evaluate the tribally-specific FL/CP curricula centered in their own tribal histories, language, knowledge, visions, and actions for the future. A key component of the FL/CP involved the planning and completion of community action projects (CAPs) by participating families. During the final session of the program, the families present their community action projects on poster boards, with children leading the presentations. The TRTs and UNM team document narratives of what was shared and learned by the families. Results The CAPs provide an empowerment and community benefit focus based on Paulo Freire's philosophy that people can become agents of change if they identify and work on issues that are important to them. The community action projects are also centered in Indigenous values and practices of reciprocity, responsibility, and being active members of the community. Discussion The CAPs added unique contributions to the Family Listening/Circle Program as the participants' learnings were strengthened when they had the opportunity to give back to their communities. The CAPs were important to document as they illustrated the potential range of effectiveness with their capacity to empower participants to address challenges within their communities, strengthen cultural norms and values, and improve the wellbeing of community members.
Digitalization of relational space in the service triangle: The case study of retail banking

Introduction The article aims to shed light on the process of shaping the relational space of work in the service triangle through the progressive digitalization of work in retail banking industry. It addresses the following research question: how do technological shifts affect the relationships and interactions (a) between employees and supervisors, and (b) between employees and customers? Through a close examination of the redesign of the interpersonal relationships from the subjective viewpoint of front-line workers across these two levels, the paper contributes to advancing the understanding of the impact of technologies on surveillance practices, work identity and professional ethics in a key working sector with regard to digitalization and changes in professional requirements. Methods The question is addressed through a qualitative case study of retail banking in Italy. In the (retail) banking sector, the redesign of the relations between supply and demand for services is more sensitive to the changes afforded by digitalization and learning algorithms. The study was conducted with the involvement of workers and trade unionists, with whom we embarked on a constant work of re-articulation through data collection, analysis, and conceptualization. We collected a multiplicity of data for triangulation: interviews, focus groups, documents, and ethnographic notes. Results Data analysis shows how work processes and interpersonal relationships start to be redesigned across the two levels. At (a) level, two main aspects are found: the measurement of individual performance within the logic of quantification, which reduces employees to a set of measured dimensions, pushing workers into conditions of stress and competition; new surveillance practices and forms of organizational control enabled by technologies and learning algorithms. At (b) level, from being an expert with specific knowledge in the financial sector the bank employee turns into a kind of seller of any product that the algorithm decides to sell, thus ignoring the value of situated experience held by embedded, embodied social actors. Moreover, algorithms enter jurisdictional spaces traditionally controlled by knowledge workers and produce unknown outcomes concerning to whom to sell which products that cannot be clearly understood by workers. Discussion Technology contributes to engendering complex identity constructions to maintain, protect, and revise professional identity.
The EJC disassembly factor PYM is an intrinsically disordered protein and forms a fuzzy complex with RNA

The discovery of several functional interactions where one or even both partners remain disordered has demonstrated that specific interactions do not necessarily require well-defined intermolecular interfaces. Here we describe a fuzzy protein–RNA complex formed by the intrinsically unfolded protein PYM and RNA. PYM is a cytosolic protein, which has been reported to bind the exon junction complex (EJC). In the process of oskar mRNA localization in Drosophila melanogaster, removal of the first intron and deposition of the EJC are essential, while PYM is required to recycle the EJC components after localization has been accomplished. Here we demonstrate that the first 160 amino acids of PYM (PYM1–160) are intrinsically disordered. PYM1–160 binds RNA independently of its nucleotide sequence, forming a fuzzy protein–RNA complex that is incompatible with PYM’s function as an EJC recycling factor. We propose that the role of RNA binding consists in down-regulating PYM activity by blocking the EJC interaction surface of PYM until localization has been accomplished. We suggest that the largely unstructured character of PYM may act to enable binding to a variety of diverse interaction partners, such as multiple RNA sequences and the EJC proteins Y14 and Mago.
The effect of environmental stressors on growth in fish and its endocrine control

Fish body growth is a trait of major importance for individual survival and reproduction. It has implications in population, ecology, and evolution. Somatic growth is controlled by the GH/IGF endocrine axis and is influenced by nutrition, feeding, and reproductive-regulating hormones as well as abiotic factors such as temperature, oxygen levels, and salinity. Global climate change and anthropogenic pollutants will modify environmental conditions affecting directly or indirectly fish growth performance. In the present review, we offer an overview of somatic growth and its interplay with the feeding regulatory axis and summarize the effects of global warming and the main anthropogenic pollutants on these endocrine axes.
Prediction of corrosion failure probability of buried oil and gas pipeline based on an RBF neural network

Risk assessment is critical to ensure the safe operation of oil and gas pipeline systems. The core content of such risk assessment is to determine the failure probability of the pipelines quantitatively and accurately. Hence, this study combines the MATLAB neural network toolbox and adopts an Radial Basis Functions (RBF) neural network with a strong non-linear mapping relationship to build a corrosion failure probability prediction model for buried oil and gas gathering and transmission pipelines. Based on the hazard identification of pipeline corrosion failure, the model summarizes the causes of corrosion failure and determines the input and output vectors of the neural network based on the fault tree. According to the selected learning samples, through the design and training of network parameters, the RBF neural network that can predict the system failure probability is finally obtained. Taking the failure probability of 30 groups of high-pressure gathering and transmission pipelines of gas storage as an example, the capability of inputting the probability of the bottom event and outputting the probability of the top event is demonstrated through training data. Our results show that the calculated failure probability based on the fault tree analysis model is consistent with the predicted failure probability based on the RBF neural network model. Hence, the RBF neural network model is shown to be reliable in predicting the corrosion failure probability of buried pipelines.
The standards of reporting randomized trials in pets (PetSORT): Methods and development processes

Background Reporting of clinical trials conducted in client- and shelter-owned dog and cat populations is not optimal, which inhibits the ability to assess the reliability and validity of trial findings and precludes the ability to include some trials in evidence synthesis. Objective To develop a reporting guideline for parallel group and crossover trials that addresses the unique features and reporting requirements for trials conducted in client- and shelter-owned dog and cat populations. Design Consensus statement. Setting Virtual. Participants Fifty-six experts from North America, the United Kingdom, Europe, and Australia working in academia, government (research and regulatory agencies), industry, and clinical veterinary practice. Methods A steering committee created a draft checklist for reporting criteria based upon the CONSORT statement and the CONSORT extensions for reporting of abstracts and crossover trials. Each item was presented to the expert participants and was modified and presented again until >85% of participants were in agreement about the inclusion and wording of each item in the checklist. Results The final PetSORT checklist consists of 25 main items with several sub-items. Most items were modifications of items contained in the CONSORT 2010 checklist or the CONSORT extension for crossover trials, but 1 sub-item pertaining to euthanasia was created de novo. Conclusion The methods and processes used to develop this guideline represent a novel departure from those used to create other reporting guidelines, by using a virtual format. The use of the PetSORT statement should improve reporting of trials conducted in client- and shelter-owned dogs and cats and published in the veterinary research literature.
Dynamics of oral microbiome acquisition in healthy infants: A pilot study

Objectives The human oral microbiota is one of the most complex bacterial communities in the human body. However, how newborns initially acquire these bacteria remains largely unknown. In this study, we examined the dynamics of oral microbial communities in healthy infants and investigated the influence of the maternal oral microbiota on the acquisition of the infant's oral microbiota. We hypothesized that the infant oral microbial diversity increases with age. Methods One hundred and sixteen whole-salivary samples were collected from 32 healthy infants and their biological mothers during postpartum and 9- and 15-month well-infant visits. Bacterial genomic DNA was extracted and sequenced by Human Oral Microbe Identification using Next Generation Sequencing (HOMINGS) methods. The Shannon index was used to measure the microbial diversity of the infant-mother dyads (alpha diversity). The microbial diversity between the mother-infant dyads (beta-diversity) was calculated using the weighted non-phylogenetic Bray-Curtis distance in QIIME 1.9. 1. Core microbiome analysis was performed using MicrobiomeAnalyst software. Linear discriminant analysis coupled with effect size analysis was used to identify differentially abundant features between mother and infant dyads. Results A total of 6,870,571 16S rRNA reads were generated from paired mother–infant saliva samples. Overall, oral microbial profiles significantly differed between the mother and infant groups (p < 0.001). The diversity of the salivary microbiomes in the infants increased in an age-dependent manner, whereas the core microbiome of the mothers remained relatively stable during the study period. Breastfeeding and gender did not affect the microbial diversity in infants. Moreover, infants had a greater relative abundance of Firmicutes and a lower abundance of Actinobacteria, Bacteroidetes, Fusobacteria, and Proteobacteria than their mothers. The SparCC correlation analysis demonstrated constant changes in infants' oral microbial community network (p < 0.05). Conclusions This study provides new evidence that the oral cavities of infants are colonized by a distinct group of bacterial species at birth. The acquisition and diversity of changes in oral microbial composition are dynamic during the first year of an infant's life. Before reaching the second birthday, the composition of the oral microbial community could be more similar to that of their biological mothers.
Mapping biodiversity and cultural values complemented with understanding of social dynamics provides effective means for addressing opportunities for nature conservation in a cultural landscape

The ecosystem services framework can usefully complement biodiversity assessments in developing socially robust nature conservation strategies in protected areas and beyond. However, there is still little research, especially in Eastern Europe, which links biodiversity assessment and nature related values to the deeper social-economic dynamics and aspirations existing in the local communities. Here we address this knowledge gap with a study case from Romania. We used data from a thorough biodiversity survey to map the protected species and habitats in a Natura 2000 area. Then we used participatory mapping with key local community representatives to understand the type of values linking the local community with the protected area, distinguishing between the past (1960’s-1989 period) and present. We identified that socio-economic and cultural values were strong and synergistically manifested in the past but not in the present. A dramatic abandonment of land use practices was reported. The current distribution of protected species and habitats does not overlap with the farmed areas in the past and present. Interviewees report that the local community went through dramatic changes from the past to present: increased individualism weakened or lost local rules, diversifying individual aspirations, low level of collective actions and weak alignment between knowledge and aspirations and the protected area. New socio-cultural values are represented by educational activities, however, with a lack of genuine local community engagement. Key directions identified by participants for the future of the site were nature friendly activities such as tourism, biking trails, forestry, and the renewal of viticulture.
Combined angiotensin-converting enzyme and aminopeptidase inhibition for treatment of experimental ventilator-induced lung injury in mice

Introduction: Ventilator-induced lung injury (VILI) may aggravate critical illness. Although angiotensin-converting enzyme (ACE) inhibition has beneficial effects in ventilator-induced lung injury, its clinical application is impeded by concomitant hypotension. We hypothesized that the aminopeptidase inhibitor ALT-00 may oppose the hypotension induced by an angiotensin-converting enzyme inhibitor, and that this combination would activate the alternative renin-angiotensin system (RAS) axis to counteract ventilator-induced lung injury. Methods: In separate experiments, C57BL/6 mice were mechanically ventilated with low (LVT, 6 mL/kg) and high tidal volumes (HVT, 30 mL/kg) for 4 h or remained unventilated (sham). High tidal volume-ventilated mice were treated with lisinopril (0.15 μg/kg/min) ± ALT-00 at 2.7, 10 or 100 μg/kg/min. Blood pressure was recorded at baseline and after 4 h. Lung histology was evaluated for ventilator-induced lung injury and the angiotensin (Ang) metabolite profile in plasma (equilibrium levels of Ang I, Ang II, Ang III, Ang IV, Ang 1-7, and Ang 1-5) was measured with liquid chromatography tandem mass spectrometry at the end of the experiment. Angiotensin concentration-based markers for renin, angiotensin-converting enzyme and alternative renin-angiotensin system activities were calculated. Results: High tidal volume-ventilated mice treated with lisinopril showed a significant drop in the mean arterial pressure at 4 h compared to baseline, which was prevented by adding ALT-00 at 10 and 100 μg/kg/min. Ang I, Ang II and Ang 1-7 plasma equilibrium levels were elevated in the high tidal volumes group versus the sham group. Lisinopril reduced Ang II and slightly increased Ang I and Ang 1-7 levels versus the untreated high tidal volumes group. Adding ALT-00 at 10 and 100 μg/kg/min increased Ang I and Ang 1-7 levels versus the high tidal volume group, and partly prevented the downregulation of Ang II levels caused by lisinopril. The histological lung injury score was higher in the high tidal volume group versus the sham and low tidal volume groups, and was attenuated by lisinopril ± ALT-00 at all dose levels. Conclusion: Combined angiotensin-converting enzyme plus aminopeptidase inhibition prevented systemic hypotension and maintained the protective effect of lisinopril. In this study, a combination of lisinopril and ALT-00 at 10 μg/kg/min appeared to be the optimal approach, which may represent a promising strategy to counteract ventilator-induced lung injury that merits further exploration.
3D printed plates based on generative design biomechanically outperform manual digital fitting and conventional systems printed in photopolymers in bridging mandibular bone defects of critical size in dogs

Conventional plate osteosynthesis of critical-sized bone defects in canine mandibles can fail to restore former functionality and stability due to adaption limits. Three-dimensional (3D) printed patient-specific implants are becoming increasingly popular as these can be customized to avoid critical structures, achieve perfect alignment to individual bone contours, and may provide better stability. Using a 3D surface model for the mandible, four plate designs were created and evaluated for their properties to stabilize a defined 30 mm critical-size bone defect. Design-1 was manually designed, and further shape optimized using Autodesk® Fusion 360 (ADF360) and finite element analysis (FE) to generate Design-2. Design-4 was created with the generative design (GD) function from ADF360 using preplaced screw terminals and loading conditions as boundaries. A 12-hole reconstruction titanium locking plate (LP) (2.4/3.0 mm) was also tested, which was scanned, converted to a STL file and 3D printed (Design-3). Each design was 3D printed from a photopolymer resin (VPW) and a photopolymer resin in combination with a thermoplastic elastomer (VPWT) and loaded in cantilever bending using a customized servo-hydraulic mechanical testing system; n = 5 repetitions each. No material defects pre- or post-failure testing were found in the printed mandibles and screws. Plate fractures were most often observed in similar locations, depending on the design. Design-4 has 2.8–3.6 times ultimate strength compared to other plates, even though only 40% more volume was used. Maximum load capacities did not differ significantly from those of the other three designs. All plate types, except D3, were 35% stronger when made of VPW, compared to VPWT. VPWT D3 plates were only 6% stronger. Generative design is faster and easier to handle than optimizing manually designed plates using FE to create customized implants with maximum load-bearing capacity and minimum material requirements. Although guidelines for selecting appropriate outcomes and subsequent refinements to the optimized design are still needed, this may represent a straightforward approach to implementing additive manufacturing in individualized surgical care. The aim of this work is to analyze different design techniques, which can later be used for the development of implants made of biocompatible materials.