Miracle-dz/UniFAR-FTUs huggingface dataset:
Covalent Functionalization of Bioengineered Polyhydroxyalkanoate Spheres Directed by Specific Protein-Protein Interactions

Bioengineered polyhydroxyalkanoate (PHA) spheres assembled in engineered bacteria are showing promising potential in protein immobilization for high-value applications. Here, we have designed innovative streamlined approaches to add functional proteins from complex mixtures (e.g., without prior purification) to bioengineered PHA spheres directly harnessing the specificity of the SpyTag/SpyCatcher mediated protein ligation. Escherichia coli was engineered to assemble PHA spheres displaying the SpyCatcher domain while simultaneously producing a SpyTagged target protein, which was in vivo specifically ligated to the PHA spheres. To further demonstrate the specificity of this ligation reaction, we incubated isolated SpyCatcher-coated PHA spheres with cell lysates containing SpyTagged target protein, which also resulted in specific ligation mediating surface functionalization. An even cruder approach was used by lysing a mixture of cells, either producing PHA spheres or target protein, which resulted in specific surface functionalization suggesting that ligation between the SpyCatcher-coated PHA spheres and the SpyTagged target proteins is highly specific. To expand the design space of this general modular approach toward programmable multifunctionalization, e.g., one-pot construction of immobilized multienzyme cascade systems on PHA spheres, we designed various recombinant bimodular PHA spheres utilizing alternative Tag/Catcher pairs (e.g., SnoopTag/SnoopCatcher and SdyTag/SdyCatcher systems). One of our bimodular PHA spheres resulted in simultaneous multifunctionalization of plain PHA spheres in one-step with two differently tagged proteins under in vitro and ex vivo reaction conditions while remaining functional. Our bimodular PHA spheres also showed high orthogonality with the non-target peptide tag and exhibited decent robustness against repeated freeze-thaw treatment. We demonstrated the utility of these approaches by using a fluorescent protein, a monomeric amylase, and a dimeric organophosphate hydrolase as target proteins. We established a versatile toolbox for dynamic functionalization of PHA spheres for biomedical and industrial applications.
Perception of Caregiving During Childhood is Related to Later Executive Functions and Antisocial Behavior in At-Risk Boys

Executive functions are considered essential for effective navigation in the social world. Parental responsiveness is a critical ingredient for normative social development and, as such, may be connected with the development of executive functions. Disruption of this development may, in turn, lead to maladaptive and antisocial behaviors. The purpose of this study was to evaluate the nature of the connections among perceived patterns of caregiving experienced in childhood, executive functions, and antisocial behaviors in at-risk adolescents. Seventy-one adolescent boys were recruited from two high-schools for adolescents who were not deemed suitable for regular schooling due to behavioral and emotional issues. Executive functions were tested using a computer-administered neuropsychological battery (CANTAB), and maternal parenting experiences and antisocial behaviors were assessed using retrospective and current questionnaires. Structural equation modeling (SEM) approach was employed to examine whether executive functions mediated the relationship between children's perceived patterns of maternal care and subsequent development of antisocial behaviors. Although maternal care had a significant direct effect on executive function (standardized coefficient = .49, p = .03) and antisocial behavior (standardized coefficient = .53, p = .05), SEM demonstrated no mediating relationships among these variables. Instead, maternal care predicted unique variance in both executive functions (standardized coefficient = .61, p = .02) and antisocial behavior (standardized coefficient = .51, p = .05). This study suggests a link between the experience of childhood caregiving and adolescent executive functions and delinquency and highlights the importance of early parenting interventions to aid executive function development. Such early interventions could potentially enhance long-term pro-social behavior.
Explorative Meta-Analysis of 377 Extant Fungal Genomes Predicted a Total Mycobiome Functionality of 42.4 Million KEGG Functions

Unveiling the relationship between taxonomy and function of the microbiome is crucial to determine its contribution to ecosystem functioning. However, while there is a considerable amount of information on microbial taxonomic diversity, our understanding of its relationship to functional diversity is still scarce. Here, we used a meta-analysis of completely annotated extant genomes of 377 taxonomically distinct fungal species to predict the total fungal microbiome functionality on Earth with accumulation curves (ACs) of all known functions from the level 3 of KEGG Orthology using both parametric and non-parametric estimates in an explorative data-mining approach. The unsaturated model extrapolating functional diversity as a function of species richness described the ACs significantly better than the saturated model that assumed a limited total number of functions, which suggested the presence of widespread and rare functions. Based on previous estimates of 3.8 million fungal species on Earth, we propagated the unsaturated model to predict a total of 42.4 ± 0.5 million KEGG level 3 functions of which only 0.06% are known today. Our approach not only highlights the presence of widespread and rare functions but points toward the necessity of novel and more sophisticated methods to unveil the entirety of functions to fully understand the involvement of the fungal microbiome in ecosystem functioning.
Diverse Roles of PUF Proteins in Germline Stem and Progenitor Cell Development in C. elegans

Stem cell development depends on post-transcriptional regulation mediated by RNA-binding proteins (RBPs) (Zhang et al., 1997; Forbes and Lehmann, 1998; Okano et al., 2005; Ratti et al., 2006; Kwon et al., 2013). Pumilio and FBF (PUF) family RBPs are highly conserved post-transcriptional regulators that are critical for stem cell maintenance (Wickens et al., 2002; Quenault et al., 2011). The RNA-binding domains of PUF proteins recognize a family of related sequence motifs in the target mRNAs, yet individual PUF proteins have clearly distinct biological functions (Lu et al., 2009; Wang et al., 2018). The C. elegans germline is a simple and powerful model system for analyzing regulation of stem cell development. Studies in C. elegans uncovered specific physiological roles for PUFs expressed in the germline stem cells ranging from control of proliferation and differentiation to regulation of the sperm/oocyte decision. Importantly, recent studies started to illuminate the mechanisms behind PUF functional divergence. This review summarizes the many roles of PUF-8, FBF-1, and FBF-2 in germline stem and progenitor cells (SPCs) and discusses the factors accounting for their distinct biological functions. PUF proteins are conserved in evolution, and insights into PUF-mediated regulation provided by the C. elegans model system are likely relevant for other organisms.
Fifteen-Year Application of Manure and Chemical Fertilizers Differently Impacts Soil ARGs and Microbial Community Structure

Manure, which contains large amounts of antibiotics and antibiotic resistance genes (ARGs), is widely used in agricultural soils and may lead to the evolution and dispersal of ARGs in the soil environment. In the present study, soils that received manure or chemical fertilizers for 15 years were sampled on the North China Plain (NCP), which is one of the primary areas of intensive agriculture in China. High-throughput quantitative PCR and sequencing technologies were employed to assess the effects of long-term manure or chemical fertilizer application on the distribution of ARGs and microbial communities. A total of 114 unique ARGs were successfully amplified from all soil samples. Manure application markedly increased the relative abundance and detectable numbers of ARGs, with up to 0.23 copies/16S rRNA gene and 81 unique ARGs. The increased abundance of ARGs in manure-fertilized soil was mainly due to the manure increasing the abundance of indigenous soil ARGs. In contrast, chemical fertilizers only moderately affected the diversity of ARGs and had no significant effect on the relative abundance of the total ARGs. In addition, manure application increased the abundance of mobile genetic elements (MGEs), which were significantly and positively correlated with most types of ARGs, indicating that horizontal gene transfer via MGEs may play an important role in the spread of ARGs. Furthermore, the application of manure and chemical fertilizers significantly affected microbial community structure, and variation partitioning analysis showed that microbial community shifts represented the major driver shaping the antibiotic resistome. Taken together, our results provide insight into the long-term effects of manure and chemical fertilization on the dissemination of ARGs in intensive agricultural ecosystems.
Analyzing Event-Related Transients: Confidence Intervals, Permutation Tests, and Consecutive Thresholds

Fiber photometry has enabled neuroscientists to easily measure targeted brain activity patterns in awake, freely behaving animal. A focus of this technique is to identify functionally-relevant changes in activity around particular environmental and/or behavioral events, i.e., event-related activity transients (ERT). A simple and popular approach to identifying ERT is to summarize peri-event signal [e.g., area under the curve (AUC), peak activity, etc.,] and perform standard analyses on this summary statistic. We highlight the various issues with this approach and overview straightforward alternatives: waveform confidence intervals (CIs) and permutation tests. We introduce the rationale behind these approaches, describe the results of Monte Carlo simulations evaluating their effectiveness at controlling Type I and Type II error rates, and offer some recommendations for selecting appropriate analysis strategies for fiber photometry experiments.
Evolutionary Origin of the P2X7 C-ter Region: Capture of an Ancient Ballast Domain by a P2X4-Like Gene in Ancient Jawed Vertebrates

P2X purinergic receptors are extracellular ATP-gated ion channel receptors present on the cell plasma membrane. P2X receptors have been found in Metazoa, fungi, amoebas, and in plants. In mammals, P2X7 is expressed by a large number of cell types and is involved in inflammation and immunity. Remarkably, P2X7 does not desensitize as other P2X do, a feature linked to a “C-cysteine anchor” intra-cytoplasmic motif encoded by exon 11. Another specific feature of P2X7 is its C-terminal cytoplasmic ballast domain (exon 13) which contains a zinc (Zn) coordinating cysteine motif and a GDP-binding region. To determine the origin of P2X7, we analyzed and compared sequences and protein motifs of the C-terminal intra-cytoplasmic region across all main groups of Metazoa. We identified proteins with typical ballast domains, sharing a remarkably conserved Zn-coordinating cysteine motif. Apart from vertebrates, these ballast domains were not associated with a typical P2X architecture. These results strongly suggest that P2X7 resulted from the fusion of a P2X gene, highly similar to P2X4, with an exon encoding a ballast domain. Our work brings new evidence on the origin of the P2X7 purinergic receptor and identifies the Zn-coordinating cysteine domain as the fundamental feature of the ancient ballast fold.
Metacognitive Beliefs as Predictors of Return to Work After Intensive Return-to-Work Rehabilitation in Patients With Chronic Pain, Chronic Fatigue and Common Psychological Disorders: Results From a Prospective Trial

Background Metacognitions are associated with work status, but no research has examined to what extent metacognitions before treatment and change in metacognitions following treatment predict return to work (RTW) prospectively. The present study aims to address these two gaps in knowledge. Methods 212 patients on long-term sick leave (>8 weeks) with extensive fatigue, chronic pain conditions and/or mental distress received 3.5 weeks of intensive rehabilitation treatment, aimed at returning them to work. Only part of the population (n = 137) had complete follow-up data on metacognitions. Metacognitions were measured with the Metacognitions Questionnaire 30 (MCQ-30), while RTW was measured using official registry data from the Norwegian Labor and Welfare Service. A registry record of participation in competitive work ≥2.5 days (50% work participation) per week, averaging over 14 weeks, was chosen as an outcome reflecting a successful RTW. The registry data spanned a total of 56 weeks per participant. Results Our results indicated that baseline MCQ scores was not associated with RTW. This was analyzed for the total MCQ score as well as for all subscales. We observed substantial changes in metacognitions following treatment, and a 1-point change in the total sum of metacognitive beliefs was associated with 5% greater odds for successful RTW at all time points (p = 0.040), while a 1-point change on the subscale of beliefs about the need to control thoughts gave 20% greater odds for successful RTW (p = 0.016). Conclusion Metacognitions concerning the need to control thoughts appear to have a significant influence on patients return to work. Here, we observed that a change in these beliefs following treatment substantially affected RTW over the course of 1 year.
Airborne microbial biodiversity and seasonality in Northern and Southern Sweden

Microorganisms are essential constituents of ecosystems. To improve our understanding of how various factors shape microbial diversity and composition in nature it is important to study how microorganisms vary in space and time. Factors shaping microbial communities in ground level air have been surveyed in a limited number of studies, indicating that geographic location, season and local climate influence the microbial communities. However, few have surveyed more than one location, at high latitude or continuously over more than a year. We surveyed the airborne microbial communities over two full consecutive years in Kiruna, in the Arctic boreal zone, and Ljungbyhed, in the Southern nemoral zone of Sweden, by using a unique collection of archived air filters. We mapped both geographic and seasonal differences in bacterial and fungal communities and evaluated environmental factors that may contribute to these differences and found that location, season and weather influence the airborne communities. Location had stronger influence on the bacterial community composition compared to season, while location and season had equal influence on the fungal community composition. However, the airborne bacterial and fungal diversity showed overall the same trend over the seasons, regardless of location, with a peak during the warmer parts of the year, except for the fungal seasonal trend in Ljungbyhed, which fluctuated more within season. Interestingly, the diversity and evenness of the airborne communities were generally lower in Ljungbyhed. In addition, both bacterial and fungal communities varied significantly within and between locations, where orders like Rhizobiales, Rhodospirillales and Agaricales dominated in Kiruna, whereas Bacillales, Clostridiales and Sordariales dominated in Ljungbyhed. These differences are a likely reflection of the landscape surrounding the sampling sites where the landscape in Ljungbyhed is more homogenous and predominantly characterized by artificial and agricultural surroundings. Our results further indicate that local landscape, as well as seasonal variation, shapes microbial communities in air.
Activities of Daily Living and Life-Space Mobility in Older Adults with Chronic Obstructive Pulmonary Disease

Purpose: The aim of this study was to investigate whether limitation during the performance of activities of daily living (ADL) was associated with life-space mobility in older people with chronic obstructive pulmonary disease (COPD), and to generate a regression model for life-space mobility score. Patients and Methods: This cross-sectional study with a convenience sample included older people (aged ≥ 60 years old) with COPD. We assessed participants ’ lung function (spirometry), life-space mobility (University of Alabama at Birmingham Study of Aging Life-Space Assessment questionnaire), severity of dyspnea (Modi ﬁ ed Dyspnea Index) and limitation during the performance of ADL (London Chest Activity of Daily Living). We used Pearson ’ s correlation to investigate the associations between the measures, and multiple linear regression to detect which of the measures in ﬂ uenced life-space mobility. Statistical signi ﬁ cance was set at 5%. Results: Fifty participants completed all the assessments (29 females [58%]; mean ± SD age of 67 ± 6 years old, FEV 1 47 ± 29% of predicted, and body mass index 22.5 ± 11.6 kg/m 2 ). Their mean scores for life-space mobility and for limitation during the performance of ADL were 49.7 ± 27.2 and 16.46 ± 9.74, respectively. We found a strong inverse correlation between limitation during the performance of ADL and life-space mobility (r = − 0.57, p = <0.01) as well as between severity of dyspnea and life-space mobility (r= 0.86, p= <0.01). Both sex and limitation during the performance of ADL were considered as independent factors associated to life-space mobility (R 2 = 0.56). Conclusion: In this study, limitations during the performance of ADL and dyspnea had a strong correlation with life-space mobility in older adults with COPD. Also, alongside sex, the limitation during the performance of ADL is an independent factor associated with lifespace mobility in a regression model.
Silver Decorated Mesoporous Carbons for the Treatment of Acute and Chronic Wounds, in a Tissue Regeneration Context

Introduction Silver decorated mesoporous carbons are interesting systems that may offer effective solutions for advanced wound care products by combining the well-known anti-microbial activity of silver nanoparticles with the versatile properties of ordered mesoporous carbons. Silver is being used as a topical antimicrobial agent, especially in wound repair. However, while silver shows bactericidal properties, it is also cytotoxic at high concentrations. Therefore, the incorporation of silver into ordered mesoporous carbons allows to exploit both silver’s biological effects and mesoporous carbons’ biocompatibility and versatility with the purpose of conceiving silver-doped materials in light of the growing health concern in wound care. Methods The wound healing potential of an ordered mesoporous carbon also doped with two different loadings of silver nanoparticles (2 wt% and 10 wt%), was investigated through a biological assessment study based on different assays (cell viability, inflammation, antibacterial tests, macrophage-conditioned fibroblast and human keratinocyte cell cultures). Results The results show silver-doped ordered mesoporous carbons to positively condition cell viability, with a cell viability percentage >70% even for 10 wt% Ag, to modulate the expression of inflammatory cytokines and of genes involved in tissue repair (KRT6a, VEGFA, IVN) and remodeling (MMP9, TIMP3) in different cell systems. Furthermore, along with the biocompatibility and the bioactivity, the silver-doped ordered mesoporous carbons still retain an antibacterial effect, as shown by a maximum of 13.1% of inhibited area in the Halo test. The obtained results clearly showed that the silver-doped ordered mesoporous carbons exhibit both good biocompatibility and antibacterial effect with enhanced re-epithelialization, angiogenesis promotion and tissue regeneration. Discussion These findings suggest that the exceptional properties of silver-doped ordered mesoporous carbons could be exploited in the treatment of acute and chronic wounds and that such carbon materials could be potential candidates for use in medical devices for wound healing purposes, in particular, the 10 wt% loading, as the results showed to be the most effective.
The Clinical Significance of PPEF1 as a Promising Biomarker and Its Potential Mechanism in Breast Cancer

Background Breast cancer (BC) is the leading cause of malignancy death in females worldwide. While intense efforts have been made to elucidate the pathogeny, the molecular mechanism of BC remains elusive. Thus, this study aimed to investigate the role of PPEF1 in the progression of BC and further explore the better clinical significance. Methods The diagnostic and prognostic values of elevated PPEF1 expression in BC were unveiled via public databases analysis. In addition, Gene Ontology (GO), Gene Set Enrichment Analysis (GSEA) and Protein–protein interaction (PPI) analysis were performed to explore the potential functions and molecular mechanisms of PPEF1 in BC progression. Experimentally, transwell and CCK-8 assays were carried out to estimate the effects of PPEF1 on the BC metastasis. Meanwhile, the differential expressions of PPEF1 in paraffin-embedded tissues and serum samples were, respectively, analyzed by Immunohistochemical (IHC) analysis and enzyme-linked immunosorbent assay (ELISA) kit. Results The transcriptional levels of PPEF1 were higher in BC than in normal breast tissues or adjacent normal tissues. Moreover, survival analysis revealed that higher PPEF1 expression was negatively associated with overall survival (OS), all events-free (AE-free) and metastatic recurrence-free (MR-free) survival, and further was an independent risk factor of unfavorable prognosis in BC patients. Additionally, the present study provided the first evidence that PPEF1 participated in multiple biological processes and underly signaling pathways involving in tumorigenesis and development of BC. Furthermore, PPEF1 promotes the BC progression and can be used as a noninvasive diagnostic marker. Noteworthy, the combined determination of serum PPEF1 and traditional tumor markers can enhance diagnostic accuracy thus is of vital importance in the early diagnosis of BC. Conclusion PPEF1 exerted a tumorigenic role and involved in molecular mechanism of tumorigenesis in BC which served as a promising biomarker for prognosis and diagnosis.
Assessment of Search Strategies in Literature-Review-Based Candidate Theses Within a Nursing Program

Background The majority of candidate theses in baccalaureate nursing programs in Sweden are written as literature studies. Being able to carry out a systematic and structured literature search is an essential part of thesis-related work. Aim The aim of the current study was to investigate changes in nursing students’ search strategies in candidate theses. Methods A retrospective, quantitative study design was obtained. Librarians (n = 2) and teachers (n = 4) randomly examined selected candidate theses (every third thesis, n = 89) from the years 2012, 2014, and 2016. Results The result showed a significant improvement over the years (from 2012 and 2014 to 2016) regarding the use of a sufficient number of synonyms, matching search terms to the respective database, use of the Boolean operator OR, and the use of subject headings and free text searches. Use of the title/abstract search largely disappeared. There was a significant change in the types of searches being done. The searches have become more structured in later years as the use of block searches increased significantly; in other words, more systematic and relevant searches have been done in recent years. Conclusion The result of this study shows that the quality of the students’ search strategies improved significantly during the studied years. It is recommended that search documents are used in both formative and summative assessments to evaluate students’ search strategies. Educational development in the form of enhanced collaboration between librarians and teachers in nursing programs is recommended because it might help to develop student search strategies in literature-based candidate theses.