Miracle-dz/UniFAR-FTUs huggingface dataset:
Osteogenic differentiation system based on biopolymer nanoparticles for stem cells in simulated microgravity

An efficient long-term intracellular growth factor release system in simulated microgravity for osteogenic differentiation was prepared based on polylactic acid (PLA) and polyhydroxyalkanoate (PHA) nanoparticles (NPs) for loading of bone morphogenetic protein 2 (BMP2) and bone morphogenetic protein 7 (BMP7) (defined as sB2-PLA-NPs and sB7-PHA-NPs), respectively, associated with osteogenic differentiation of human adipose derived stem cells (hADSCs). On account of soybean lecithin (SL) as biosurfactants, sB2-PLA-NPs and sB7-PHA-NPs had a high encapsulation efficiency (>80%) of BMPs and uniform small size (<100 nm), and showed a different slow-release to provide BMP2 in early stage and BMP7 in late stages of osteogenic differentiation within 20 d, due to degradation rate of PLA and PHA in cells. After uptake into hADSCs, by comparison with single sB2-PLA-NPs or sB7-PHA-NPs, the Mixture NPs compound of sB2-PLA-NP and sB7-PHA-NP with a mass ratio of 1:1, can well-promote ALP activity, expression of OPN and upregulated related osteo-genes. Directed osteo-differentiation of mixture NPs was similar to result of sustained free-BMP2 and BMP7-supplying (sFree-B2&B7) in simulated microgravity, which demonstrated the reliability and stability of Mixture NPs as a long-term osteogenic differentiation system in space medicine and biology in future.
Organic nitrogen nutrition: LHT1.2 protein from hybrid aspen (Populus tremula L. x tremuloides Michx) is a functional amino acid transporter and a homolog of Arabidopsis LHT1

Abstract The contribution of amino acids (AAs) to soil nitrogen (N) fluxes is higher than previously thought. The fact that AA uptake is pivotal for N nutrition in boreal ecosystems highlights plant AA transporters as key components of the N cycle. At the same time, very little is known about AA transport and respective transporters in trees. Tree genomes may contain 13 or more genes encoding the lysine histidine transporter (LHT) family proteins, and this complicates the study of their significance for tree N-use efficiency. With the strategy of obtaining a tool to study N-use efficiency, our aim was to identify and characterize a relevant AA transporter in hybrid aspen (Populus tremula L. x tremuloides Michx.). We identified PtrLHT1.2, the closest homolog of Arabidopsis thaliana (L.) Heynh AtLHT1, which is expressed in leaves, stems and roots. Complementation of a yeast AA uptake mutant verified the function of PtrLHT1.2 as an AA transporter. Furthermore, PtrLHT1.2 was able to fully complement the phenotypes of the Arabidopsis AA uptake mutant lht1 aap5, including early leaf senescence-like phenotype, reduced growth, decreased plant N levels and reduced root AA uptake. Amino acid uptake studies finally showed that PtrLHT1.2 is a high affinity transporter for neutral and acidic AAs. Thus, we identified a functional AtLHT1 homolog in hybrid aspen, which harbors the potential to enhance overall plant N levels and hence increase biomass production. This finding provides a valuable tool for N nutrition studies in trees and opens new avenues to optimizing tree N-use efficiency.
An integrated, modular approach to data science education in microbiology

We live in an increasingly data-driven world, where high-throughput sequencing and mass spectrometry platforms are transforming biology into an information science. This has shifted major challenges in biological research from data generation and processing to interpretation and knowledge translation. However, postsecondary training in bioinformatics, or more generally data science for life scientists, lags behind current demand. In particular, development of accessible, undergraduate data science curricula has the potential to improve research and learning outcomes as well as better prepare students in the life sciences to thrive in public and private sector careers. Here, we describe the Experiential Data science for Undergraduate Cross-Disciplinary Education (EDUCE) initiative, which aims to progressively build data science competency across several years of integrated practice. Through EDUCE, students complete data science modules integrated into required and elective courses augmented with coordinated cocurricular activities. The EDUCE initiative draws on a community of practice consisting of teaching assistants (TAs), postdocs, instructors, and research faculty from multiple disciplines to overcome several reported barriers to data science for life scientists, including instructor capacity, student prior knowledge, and relevance to discipline-specific problems. Preliminary survey results indicate that even a single module improves student self-reported interest and/or experience in bioinformatics and computer science. Thus, EDUCE provides a flexible and extensible active learning framework for integration of data science curriculum into undergraduate courses and programs across the life sciences.
Entrepreneurs and Burnout. How Hardy Personality works in this process

Background Considering the importance of entrepreneurship and the impact of burnout on workers’ health, this study aims to explore the presence of burnout in entrepreneurs and the interaction of hardy personality (HP) in this process. Method The sample included 255 Spanish entrepreneurs. Occupational factors, working hours, labour immersion, HP, burnout syndrome (i.e. Emotional exhaustion, Depersonalization and Lack of accomplishment) and burnout consequences were assessed. Results Descriptive analysis showed that entrepreneurs had low levels of occupational factors, burnout syndrome and consequences. Hierarchical regression exploratory results indicated that working hours, labour immersion, and Emotional exhaustion were the most relevant predictors of the consequences. Besides, mediation models with PROCESS macro (v.3.0) highlighted the indirect effect of occupational factors and showed that emotional exhaustion was the only component of burnout that mediated in between the predictors and the consequences. As well, HP moderated the relationship between occupational factors and emotional exhaustion. Conclusions Occupational factors are the main predictor of burnout in entrepreneurs and HP could prevent their effect on Emotional exhaustion. The results suggest the importance of training to promote HP for better health and performance of entrepreneurs.
Change detection of auditory tonal patterns defined by absolute versus relative pitch information. A combined behavioural and EEG study

The human auditory system often relies on relative pitch information to extract and identify auditory objects; such as when the same melody is played in different keys. The current study investigated the mental chronometry underlying the active discrimination of unfamiliar melodic six-tone patterns by measuring behavioural performance and event-related potentials (ERPs). In a roving standard paradigm, such patterns were either repeated identically within a stimulus train, carrying absolute frequency information about the pattern, or shifted in pitch (transposed) between repetitions, so only relative pitch information was available to extract the pattern identity. Results showed that participants were able to use relative pitch to detect when a new melodic pattern occurred. Though in the absence of absolute pitch sensitivity significantly decreased and behavioural reaction time to pattern changes increased. Mismatch-Negativity (MMN), an ERP indicator of auditory deviance detection, was elicited at approximately 206 ms after stimulus onset at frontocentral electrodes, even when only relative pitch was available to inform pattern discrimination. A P3a was elicited in both conditions, comparable in amplitude and latency. Increased latencies but no differences in amplitudes of N2b, and P3b suggest that processing at higher levels is affected when, in the absence of absolute pitch cues, relative pitch has to be extracted to inform pattern discrimination. Interestingly, the response delay of approximately 70 ms on the behavioural level, already fully manifests at the level of N2b. This is in accordance with recent findings on implicit auditory learning processes and suggests that in the absence of absolute pitch cues a slowing of target selection rather than a slowing of the auditory pattern change detection process causes the deterioration in behavioural performance.
Declining trend of smoking and smokeless tobacco in India: A decomposition analysis

There has been a relative reduction of tobacco consumption between Global Adult Tobacco Survey-India (GATS-India) 2009–10 and GATS-India 2016–17. However, in terms of absolute numbers, India still has the highest number of tobacco consumers. Therefore, this paper aims to examine the socioeconomic correlates and delineate the factors contributing to a change in smoking and smokeless tobacco use from GATS (2009–10) to GATS (2016–17) in India. We used multivariable binary logistic regressions to examine the demographic and socioeconomic correlates of smoking and smokeless tobacco use for both the rounds of the survey. Further decomposition analysis has been applied to examine the specific contribution of factors in the decline of tobacco consumption over a period from 2009 to 2016. Results indicated that the propensity component was primarily responsible for major tobacco consumption decline (smoking- 41%, smokeless tobacco use- 81%). Most of the decrease in propensity to smoke has been explained by residential type and occupation of the respondent. Age of the respondent contribute significantly in reducing the prevalence of smokeless tobacco consumption during the seven-year period, regardless of change in the composition of population. To achieve the National Health Policy, 2017 aim of reducing tobacco use up to 15% by 2020 and up to 30% by 2025, targeted policies and interventions addressing the inequalities identified in this study, must be developed and implemented.
Construction of a reference transcriptome for the analysis of male sterility in sugi (Cryptomeria japonica D. Don) focusing on MALE STERILITY 1 (MS1)

Sugi (Cryptomeria japonica D. Don) is an important conifer used for afforestation in Japan. As the genome of this species is 11 Gbps, it is too large to assemble within a short timeframe. Transcriptomics is one approach that can address this deficiency. Here we designed a workflow consisting of three stages to de novo assemble transcriptome using Oases and Trinity. The three transcriptomic stage used were independent assembly, automatic and semi-manual integration, and refinement by filtering out potential contamination. We identified a set of 49,795 cDNA and an equal number of translated proteins. According to the benchmark set by BUSCO, 87.01% of cDNAs identified were complete genes, and 78.47% were complete and single-copy genes. Compared to other full-length cDNA resources collected by Sanger and PacBio sequencers, the extent of the coverage in our dataset was the highest, indicating that these data can be safely used for further studies. When two tissue-specific libraries were compared, there were significant expression differences between male strobili and leaf and bark sets. Moreover, subtle expression difference between male-fertile and sterile libraries were detected. Orthologous genes from other model plants and conifer species were identified. We demonstrated that our transcriptome assembly output (CJ3006NRE) can serve as a reference transcriptome for future functional genomics and evolutionary biology studies.
Mismatch Repair (MMR) gene alteration and BRAF V600E mutation are potential predictive biomarkers of immune checkpoint inhibitors in MMR-deficient colorectal cancer.

BACKGROUND Immune checkpoint inhibitor (ICI) therapy is highly effective in metastatic mismatch repair-deficient (MMR-D) colorectal cancer (CRC). In this study, we evaluated molecular and clinical predictors of ICI response in MMR-D CRC. PATIENTS AND METHODS Patient databases at 4 cancer institutions were queried. The Fisher exact test was performed to test the association of clinical and molecular markers. The Kaplan-Meier method was used to estimate progression free survival (PFS) and compared by the log-rank test. Twelve- and 24-month PFS rates were compared by the Z test. RESULTS A total of 60 CRC patients with MMR-D/MSI-H who previously received ICI were identified. Patients with liver metastasis had a lower overall response rate (ORR) as compared to other sites of metastasis (36.4% vs 68.7%; P=0.081). Patients with MLH1/ PMS2 loss had worse 1-year and 2-year PFS rates compared to patients with MSH2/MSH6 loss (84.2% vs 57.8% and 78.2% vs 54.2%, respectively; p<0.001). There were improved 1-year and 2-year PFS rates in patients with wild-type BRAF when compared to patients with BRAF V600E mutation (73.3% vs 40%, and 73.3% vs 26.7%; respectively [P<0.001]). Patients aged >65 had significantly worse PFS rates as compared to patients aged ≤ 65 (P<0.001). CONCLUSION BRAF V600E mutation, MLH1 and/or PMS2 loss, as well as age >65 years and liver metastasis may be predictive of duration of ICI response in MMR-deficient CRC patients. Larger cohorts are needed to confirm our findings. IMPLICATIONS FOR PRACTICE This results of this original research article reveals clinically important biomarkers that potentially predict immune checkpoint inhibitor response in mismatch repair deficient colorectal cancer patients.
Targeting eIF4A-Dependent Translation of KRAS Signaling Molecules

These findings document the coordinate, eIF4A-dependent translation of RAS-related oncogenic signaling molecules and demonstrate therapeutic efficacy of eIF4A blockade in pancreatic adenocarcinoma. Pancreatic adenocarcinoma (PDAC) epitomizes a deadly cancer driven by abnormal KRAS signaling. Here, we show that the eIF4A RNA helicase is required for translation of key KRAS signaling molecules and that pharmacological inhibition of eIF4A has single-agent activity against murine and human PDAC models at safe dose levels. EIF4A was uniquely required for the translation of mRNAs with long and highly structured 5′ untranslated regions, including those with multiple G-quadruplex elements. Computational analyses identified these features in mRNAs encoding KRAS and key downstream molecules. Transcriptome-scale ribosome footprinting accurately identified eIF4A-dependent mRNAs in PDAC, including critical KRAS signaling molecules such as PI3K, RALA, RAC2, MET, MYC, and YAP1. These findings contrast with a recent study that relied on an older method, polysome fractionation, and implicated redox-related genes as eIF4A clients. Together, our findings highlight the power of ribosome footprinting in conjunction with deep RNA sequencing in accurately decoding translational control mechanisms and define the therapeutic mechanism of eIF4A inhibitors in PDAC. Significance: These findings document the coordinate, eIF4A-dependent translation of RAS-related oncogenic signaling molecules and demonstrate therapeutic efficacy of eIF4A blockade in pancreatic adenocarcinoma.
A dynein-associated photoreceptor protein prevents ciliary acclimation to blue light

DYBLUP is a blue light sensor protein that binds to ciliary dynein motors and regulates light acclimation. Light-responsive regulation of ciliary motility is known to be conducted through modulation of dyneins, but the mechanism is not fully understood. Here, we report a novel subunit of the two-headed f/I1 inner arm dynein, named DYBLUP, in animal spermatozoa and a unicellular green alga. This subunit contains a BLUF (sensors of blue light using FAD) domain that appears to directly modulate dynein activity in response to light. DYBLUP (dynein-associated BLUF protein) mediates the connection between the f/I1 motor domain and the tether complex that links the motor to the doublet microtubule. Chlamydomonas lacking the DYBLUP ortholog shows both positive and negative phototaxis but becomes acclimated and attracted to high-intensity blue light. These results suggest a mechanism to avoid toxic strong light via direct photoregulation of dyneins.
Facebook futures: Mark Zuckerberg’s discursive construction of a better world

This article explores the future imaginaries used in Facebook’s corporate communications. It aims to reconstruct how these “Facebook Futures” are constructed over time and across different contexts by Facebook’s CEO Mark Zuckerberg. Focus of the investigation is a discourse analysis of Zuckerberg’s public language from 2004 to 2017. By employing qualitative and interpretive modes of enquiry, this study attempts to show (1) how Facebook’s future imaginaries change over time, (2) how Facebook’s central imaginaries “global connectivity” and “global community” are substantiated, and (3) how these imaginaries are supported by norms and values inherent in Silicon Valley culture. Overall, Facebook is analyzed as an example of a prophetic corporation, not only providing an explicitly corporate vision of a better world, but also blending it with the digital technologies and practices involved in making this vision reality.
A Risk Prediction Model by LASSO for Radiation-Induced Xerostomia in Patients With Nasopharyngeal Carcinoma Treated With Comprehensive Salivary Gland–Sparing Helical Tomotherapy Technique

Objective This study aimed to develop a least absolute shrinkage and selection operator (LASSO)-based multivariable normal tissue complication probability (NTCP) model to predict radiation-induced xerostomia in patients with nasopharyngeal carcinoma (NPC) treated with comprehensive salivary gland–sparing helical tomotherapy technique. Methods and Materials LASSO with the extended bootstrapping technique was used to build multivariable NTCP models to predict factors of patient-reported xerostomia relieved by 50% and 80% compared with the level at the end of radiation therapy within 1 year and 2 years, R50-1year and R80-2years, in 203 patients with NPC. The model assessment was based on 10-fold cross-validation and the area under the receiver operating characteristic curve (AUC). Results The prediction model by LASSO with 10-fold cross-validation showed that radiation-induced xerostomia recovery could be predicted by prognostic factors of R50-1year (age, gender, T stage, UICC/AJCC stage, parotid Dmean, oral cavity Dmean, and treatment options) and R80-2years (age, gender, T stage, UICC/AJCC stage, oral cavity Dmean, N stage, and treatment options). These prediction models also demonstrated a good performance by the AUC. Conclusion The prediction models of R50-1year and R80-2years by LASSO with 10-fold cross-validation were recommended to validate the NTCP model before comprehensive salivary gland–sparing radiation therapy in patients with NPC.
Methyl Jasmonate Cytotoxicity and Chemosensitization of T Cell Lymphoma In Vitro Is Facilitated by HK 2, HIF-1α, and Hsp70: Implication of Altered Regulation of Cell Survival, pH Homeostasis, Mitochondrial Functions

Methyl jasmonate (MJ) displays antineoplastic potential against numerous neoplastic cells. However, several mechanistic aspects of its antineoplastic action against malignancies of T cell origin remain elusive. The present investigation reports the novel targets of MJ and mechanistic pathways of MJ-mediated antineoplastic and chemosensitizing action against tumor cells derived from murine T-cell lymphoma, designated as Dalton’s lymphoma (DL). The present study demonstrates that MJ directly docks to HIF-1α, hexokinase 2, and Hsp70 at prominent binding sites. MJ exhibits tumoricidal action against tumor cells via induction of apoptosis and necrosis through multiple pathways, including declined mitochondrial membrane potential, enhanced expression of ROS, altered pH homeostasis, an elevated level of cytosolic cytochrome c, and modulated expression of crucial cell survival and metabolism regulatory molecules. Additionally, this study also reports the chemosensitizing ability of MJ against T cell lymphoma accompanied by a declined expression of MDR1. This study sheds new light by demonstrating the implication of novel molecular mechanisms underlying the antitumor action of MJ against T-cell lymphoma and hence has immense translational significance.
Understanding the Link Between Maternal Overnutrition, Cardio-Metabolic Dysfunction and Cognitive Aging

Obesity has long been identified as a global epidemic with major health implications such as diabetes and cardiovascular disease. Maternal overnutrition leads to significant health issues in industrial countries and is one of the risk factors for the development of obesity and related disorders in the progeny. The wide accessibility of junk food in recent years is one of the major causes of obesity, as it is low in nutrient content and usually high in salt, sugar, fat, and calories. An excess of nutrients during fetal life not only has immediate effects on the fetus, including increased growth and fat deposition in utero, but also has long-term health consequences. Based on human studies, it is difficult to discern between genetic and environmental contributions to the risk of disease in future generations. Consequently, animal models are essential for studying the impact of maternal overnutrition on the developing offspring. Recently, animal models provided some insight into the physiological mechanisms that underlie developmental programming. Most of the studies employed thus far have focused only on obesity and metabolic dysfunctions in the offspring. These studies have advanced our understanding of how maternal overnutrition in the form of high-fat diet exposure can lead to an increased risk of obesity in the offspring, but many questions remain open. How maternal overnutrition may increase the risk of developing brain pathology such as cognitive disabilities in the offspring and increase the risk to develop metabolic disorders later in life? Further, does maternal overnutrition exacerbate cognitive- and cardio-metabolic aging in the offspring?
Stabilin-1 plays a protective role against Listeria monocytogenes infection through the regulation of cytokine and chemokine production and immune cell recruitment

Scavenger receptors are part of a complex surveillance system expressed by host cells to efficiently orchestrate innate immune response against bacterial infections. Stabilin-1 (STAB-1) is a scavenger receptor involved in cell trafficking, inflammation and cancer, however its role in infection remains to be elucidated. Listeria monocytogenes (Lm) is a major intracellular human food-borne pathogen causing severe infections in susceptible hosts. Using a mouse model of infection, we demonstrate here that STAB-1 controls Lm-induced cytokine and chemokine production and immune cell accumulation in Lm-infected organs. We show that STAB-1 also regulates the recruitment of myeloid cells in response to Lm infection and contributes to clear circulating bacteria. In addition, whereas STAB-1 appears to promote bacterial uptake by macrophages, infection by pathogenic Listeria induces the down regulation of STAB-1 expression and its delocalization from the host cell membrane. We propose STAB-1 as a new SR involved in the control of Lm infection through the regulation of host defense mechanisms, a process that would be targeted by bacterial virulence factors to promote infection.